United States
Enulronmental Protection
Agency
ECDIC-1998-45
Office of Preuentlon,
Pesticides and Toxic
Substances 7204LU
Washington, O.C. 29468
September 1993
xxxxxxx
OCM/LDIflD/SSB
GOOD LRBORRTORV PRRCTICE
STRNDRROS
INSPECTION MRNURL
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ACKNOWLEDGMENTS
The development of this manual was managed by John Helm of OCM, the EPA
Work Assignment Manager; Fred Siegelman of OCM; and Diane Bradway of
NEIC. Principal EPA contributors included Dawn Banks, Harry Day, Dean
Hill, Steve Howie, Jack McCann, Randy Morris, as well as John Helm, Diane
Bradway, and Fred Siegelman. Further assistance in the development of this
manual was provided by Science Applications International Corporation (SAIC)
in partial fulfillment of EPA Contract No. 68-D2-0157, Work Assignment 10.
DISCLAIMER
Neither the United States Government nor its employees makes any warranty,
expressed or implied, or assumes any legal liability for any third party's use of
or the results of such use of any information, product, or process discussed in
this document. Mention or illustration of company or trade names, or of
commercial products, does not constitute endorsement by the U.S. Environmental
Protection Agency (EPA).
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GOOD LABORATORY PRACTICE STANDARDS
INSPECTION MANUAL
September 1993
Prepared by:
Scientific Support Branch
Laboratory Data Integrity Assurance Division
Office of Compliance Monitoring (EN342W)
Washington, DC 20460
(703) 308-8272
National Enforcement Investigation Center Date
Box 25227, Denver Federal Center
(303) 236-8142
Approved by:
Chief, Scientific Support Branch Date
Laboratory Data Integrity Assurance Division
Office of Complianca Monitoring
Director ' Date
Laboratory Data Integrity Assurance Division
Office of Compliance Monitoring
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TAJ3LE OF
TABLE OF CONTENTS
LIST OF ACRONYMS v
1.0 INTRODUCTION . . . . 1-1
1.1 PURPOSE OF THIS MANUAL 1-1
1.2 BACKGROUND ON GOOD LABORATORY PRACTICE STANDARDS 1-2
1.3 FIFRA AND TSCA GLP STANDARDS 1-3
1.4 GLP ENFORCEMENT AUTHORITY 1-3
1.4.1 FIFRA Violations 1-3
1.4.2 TSCA Violations 1-5
1.4.3 GLP Violations 1-6
1.5 STANDARDS OF PROFESSIONAL CONDUCT 1-7
2.0 PRE-INSPECTION 2-1
2,1 INTRODUCTION 2-1
2.2 DETERMINING THE SCOPE OF THE INSPECTION 2-1
2.2.1 Compliance Reviews 2-1
2.2.2 Study Audits 2-1
2.3 INSPECTION PLANNING 2-2
2.4 REVIEWING EPA INFORMATION . 2-3
2.5 PROVIDING ADVANCE NOTIFICATION 2-3
2.5.1 Items Addressed in Advance Notification 2-*
2.6 INSPECTION TEAM COORDINATION 2-5
2.6.1 Inspection Plan 2-6
2.6.2 Pre-Inspection Meeting with Team Members 2-6
2.6.3 Preparation for Audits 2-6
2.7 GATHERING INSPECTION DOCUMENTS AND EQUIPMENT 2-7
2.7.1 Types of Documents 2-7
2.7.2 Inspection Equipment 2-9
2.8 Confidential Business Information Considerations 2-9
2.8.1 TSCA 2-9
2.8.2 FTFRA 2-11
3.0 INSPECTION PROCEDURES , 3-1
3.1 INTRODUCTION 3-1
3.2 INSPECTION AUTHORITY 3-1
3.2.1 Credentials 3-1
3.2.2 Written Notice of Inspection 3-2
3.3 PRELIMINARY STEPS FOR.CONDUCTING A GLP INSPECTION 3-2
3.4 CONSENT To ENTER AND INSPECT 3-5
3.4.1 Procedures to Gain Consent 3-5
3.4.2 Reluctance to Give Consent 3-7
3.4.3 Conditional Consent 3-7
3.4.4 Withdrawal of Consent 3-3
3.4.5 Inspector Judgment 3-3
September I99J
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TABLE OF CONTENTS
TABLE OF CONTENTS (Continued)
3.5 DENIAL OF CONSENT To ENTER AND INSPECT 3-10
3.6 THE OPENING CONFERENCE 3-11
3.6.1 Purpose 3-11
3.6.2 Procedures 3-1.2
3.7 THE CLOSING CONFERENCE 3-15
3.7.1 Purpose 3-15
3.7.2 Pre-Closing Conference with Inspection Team 3-16
3.7.3 Procedures 3-17
3.8 EVIDENCE COLLECTION AND ACCOUNTABILITY 3-22
3.8.1 Field Notebook 3-23
3.8.2 Copies of Data, Records, Reports, and Correspondence 3-23
3.8.3 Signed Statements 3-25
3.8.4 Photographs and Observations 3-26
3.8.5 Physical Sampling (Nondocumentary Samples) 3-27
3.8.6 Maintenance of Inspection Materials 3-28
3.8.7 FTFRAyTSCA Receipts 3-29
3.8.8 Investigations Involving Alleged Criminal Activity 3-29
4.0 GLP COMPLIANCE REVIEW 4-1
4.1 INTRODUCTION 4-1
4.2 FACiLrrY COMPLIANCE REVIEW 4-1
4.3 ORGANIZATION AND PERSONNEL 4-2
4.3.1 Personnel 4-2
4.3.2 Testing Facility Management 4-3
4.3.3 Study Director 4-4
4.3.4 Quality Assurance Unit 4-6
4.4 FACILITIES 4-7
4.4.1 Test Facility, General 4-7
4.4.2 Test System Care Facilities 4-8
4.4.3 Test System Supply Facilities 4-8
4.4.4 Facilities for Handling Test, Control, and Reference Substances 4-8
4.4.5 Testing Facility Operations Areas . 4-9
4.4.6 Specimen and Data Storage Facilities . . 4-9
4.5 EQUIPMENT 4-9
4.5.1 Equipment Design . 4-9
4.5.2 Maintenance and Calibration 4-9
4.6 TEsnNQ FACILITIES OPERATION 4-9
4.6.1 Standard Operating Procedures 4-9
4.6.2 Reagents and Solutions 4-10
4.6.3 Animal and Other Test System Care . . . . 4-10
4.7 TEST, CONTROL, AND' REFERENCE SUBSTANCES 4-
4.7.1 Test, Control, and Reference Substance Characterization . . 4-1
4.7.2 Test, Control, and Reference Substance Handling 4-
4.7.3 Mixture of Substances with Carriers . . 4-
4.8 PROTOCOL FOR AND CONDUCT OF A STUDY 4-
4.8.1 Protocol 4-
4.8.2 Conduct of a Study 4-
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TAJBLE OF CONTESTS
TABLE OF CONTENTS (Continued)
4.9 RECORDS AND REPORTS 4-13
4.9.1 Reporting of Study Results 4-13
4.9.2 Storage and Retrieval of Records 4-14
4.9.3 Retention of Records 4-14
4.9.4 Special Considerations for Field Sites 4-14
5.0 AUDIT PROCEDURES 5-1
5.1 INTRODUCTION 5-1
5.2 GLP COMPLIANCE 5-1
5.3 DATA REVIEW 5-3
5.4 COMMON DEFICIENCIES .5-5
5.6 SOP REFERENCE LIST 5-5
6.0 POST-INSPECTION ACTIVITIES 6-1
6.1 INTRODUCTION . . 6-1
6.2 FOLLOWUP 6-1
6.2.1 Followup Information from an Inspected Facility 6-2
6.2.2 Followup Information from a Non-Inspected Facility 6-3
6.3 THE INSPECTION REPORT 6-4
6.4.1 Elements of the Inspection Report 6-5
6.4.2 Inspection Checklists 6-6
6.4.3 CBI Considerations 6-6
6.4.4 Practical Tips for Report Preparation and Writing 6-6
APPENDICES
APPENDK A - COMPLETED NOTIFICATION LETTER
APPENDIX B - INVESTIGATION REQUEST
APPENDIX C - EXAMPLE OF REQUEST FOR FURTHER INFORMATION LETTER
APPENDIX D - GLP FIFRA COMPLIANCE CHECKLIST
APPENDIX E - GLP TSCA COMPLIANCE CHECKLIST
iii September 1993
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TABLE OF CONTENTS
LIST OF TABLES
1-1 MAJOR DIFFERENCES BETWEEN FEFRA AND TSCA M
2-1 TYPES OF EQUIPMENT 2-10
LIST OF RGURES
3-1 TSCA NOTICE OF INSPECTION 3-3
3-2 FIFRA NOTICE OF INSPECTION • 3-4
3-3 TSCA INSPECTION CONFIDENTIALITY NOTICE . 3-13
3-4 TSCA DECLARATION OF CONFIDENTIAL BUSINESS INFORMATION FORM 3-18
3-5 FTFRA RECEIPT FOR SAMPLES 3-19
3-6 TSCA RECEIPT FOR SAMPLES AND DOCUMENTS 3-20
CLP Inspection Manual iv
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TABLE OF CONTEXTS
LIST OF ACRONYMS
CAS Chemical Abstracts Service
CBI Confidential Business Information
CDO Case Development Officer
CEO Chief Executive Officer
CFR Code of Federal Regulations
CIR Comprehensive Inspection Report
DCO Document Control Officer
ERP Enforcement Response Policy
EPA Environmental Protection Agency
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act-
.FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FOIA Freedom of Information Act
GLP Good Laboratory Practice
GRC GLP Review Committee
IMD Information Management Division
LDIAD Laboratory Data Integrity Assurance Division
NEIC National Enforcement Investigation Center
OCM Office of Compliance Monitoring
OPP Office of Pesticide Programs
OPPT Office of Pollution Prevention and Toxics
QAU Quality Assurance Unit
SOP Standard Operating Procedure
SSB Scientific Support Branch
TSCA Toxic Substances Control Act
U.S.C. United States Code
September
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TAJBLS OF CONTENTS
BLANK PAGE
CLP Inspection Manual vi
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INTRODUCTION
1.0 INTRODUCTION
The U. S. Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) have
promulgated Good Laboratory Practice (GLP) Standards Regulations to assure the quality of data
submitted as part of the requirements of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA),
the Toxic Substances Control Act (TSCA), and the Federal Food, Drug, and Cosmetic Act (FFDCA).
Data submitted to EPA under either FIFRA or TSCA requirements, must be prepared in accordance with
the GLP standards. Based on an interagency agreement originated in 1978, FDA performs inspections
for compliance at health effects laboratories that engage in testing for both FDA and EPA. EPA
performs inspections to determine compliance and audit data at all other laboratories submitting to EPA
under covered parts of FIFRA and TSCA.
1.1 PURPOSE OP Tras MANUAL
Congress delegated responsibility to EPA for promulgating and enforcing rules pursuant to FIFRA and
TSCA. OCM is responsible for ensuring compliance with and enforcement of FIFRA and TSCA. A
comprehensive compliance and enforcement program is necessary to assure that OCM meets its
congressional mandate to protect health and the environment.
An integral pan of OCM's compliance program is the compliance monitoring inspection, which is
conducted to ascertain if regulated facilities are in compliance with FIFRA and TSCA regulatory
requirements. This manual is intended to provide guidance to EPA inspectors who conduct compliance
inspections related to data submitted under FIFRA Sections 3, 4, 5, 8, 18, and 24(c), and TSCA Sections
4 and 5. There are other OCM guidance materials pertaining to FIFRA and TSCA inspections and to
environmental compliance inspections in general. This manual is intended as a supplement to those
materials. Therefore, inspectors should refer to other documents as necessary when performing
inspections to determine compliance with FIFRA and TSCA.
As the objectives of EPA, and OCM, change to reflect new priorities delegated by statutory, regulatory,
or policy modifications, the methods, operations, and procedures employed by EPA in conducting GLP
inspections may also change. The inspector should be aware that EPA may from time to time issue new
Standard Operating Procedures (SOPs). These SOPs are the primary guidance documents developed by
EPA to inform GLP inspectors of current policy and procedures. As such, all current SOPs will take
precedence over the contents of this manual. In areas where this manual and newer SOPs differ, the
directives of the SOPs will be followed.
This manual provides EPA inspectors with guidance in conducting GLP inspections under both FIFRA
and TSCA. References to the applicable regulations will be for FIFRA (40 CFR Part 160) unless
otherwise noted in the text. The corresponding TSCA regulations are found at 40 CFR Pan 792.
l-l September 1993
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CHASTER ONE
1.2 BACKQKXJND ON GOOD LABORATORY PRACTICE STANDARDS
The GLP regulations were developed to address problems found with data submitted to EPA and FDA.
Investigations by these agencies in the mid-1970s revealed that some studies had not been conducted in
accordance with commonly accepted laboratory practices. Some studies had been conducted so poorly
that the resulting data could not be relied upon in EPA's regulatory decisionmaking process. As a result,
the FIFRA and TSCA GLP standards developed by EPA and FDA specify minimum practices and
procedures that must be followed to assure the quality and integrity of data submitted to EPA in support
of applications for research or marketing permits for pesticide products in the case of FIFRA and for
studies relating to health effects, environmental effects, and chemical fate in the case of TSCA.
The initial FIFRA and TSCA GLP standards were proposed in 1979, and final regulations became
effective in May 1984, several years after FDA promulgated GLP standards under its statute. The 1984
regulations did not address all studies, although EPA recognized the need to do this at some point. EPA
felt it needed more experience with some of the nonhealth effects studies in order to write GLP
regulations applicable to them. It is important to note that while the 1984 GLP regulations specified a
limited number and type of studies, the FTFRA Section 8 recordkeeping regulations [40 CFR 169.2(k)],
which require that the original raw data supporting all studies be kept for the life of the pesticide's
registration, did not. Thus, while FIFRA GLP requirements initially applied to a limited range of studies
(i.e., health effects studies), EPA's books and records requirements encompassed all types of studies
submitted to support registrations.
In August 1989, EPA published its final revised FIFRA and TSCA GLP rules, which expanded the
coverage of the GLP standards to nearly all studies submitted to EPA under FIFRA or TSCA. The
revisions also reflect changes made by FDA to its GLP regulations in 1987. EPA's revisions were made
to assure some degree of consistency among the three rules. This was done to minimize the regulatory
burden on laboratories that may conduct studies under all three statutes.
The revised TSCA GLP standards became effective on September 18, 1989, while the revised FIFRA
GLP standards became effective on October 16, 1989. The FIFRA GLP standards Regulations are
applicable to virtually any study required to be performed for submission to EPA in support of an
application for a pesticide marketing or research permit. The TSCA GLP Standards regulation applies
to any study required to be conducted to determine the effects of any chemical substance that is
manufactured, distributed, processed, used, or disposed of within the jurisdiction of the United States.
on human health and the environment. The purpose of die GLP standards is to provide some assurance
that studies are conducted with certain safeguards in place regarding data quality and integrity and that
the raw data, records, and reports will allow a study's reconstruction.
GLP Inspection Manual 1-2
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IffTXODC'CTlON
1.3 FIFRA AND TSCA GLP STANDARDS
EPA, through the Office of Compliance Monitoring (OCM), conducts GLP inspections under both TSCA
(40 CFR Part 792) and FIFRA (40 CFR Part 160) regulations. In instances where FTFRA and TSCA
differ, those differences will be cited in the ensuing sections of this manual. The two major differences
between FIFRA and TSCA involve the scope of GLP applicability and the retention of records. These
differences are shown in Table 1-1.
1.4 GLP ENFORCEMENT AUTHORITY
Violations of the GLP standards may be discovered in a number of ways. Generally, GLP violations are
likely to be found (1) during laboratory inspections conducted by EPA and FDA, (2) during EPA's
review of data submissions, or (3) through investigations of tips or complaints.
1.4.1 FIFRA Violations
Under FIFRA Section 12, it is unlawful for any person:
• To refuse to prepare, maintain, or submit any records required by or under Section 5,
7, 8, 11, or 19 [FIFRA §12(a)(2)(B)(i)].
• To refuse to submit any reports required by or under Section 5, 6, 7, 8, 11, or 19
[FIFRA §12(a)(2)(B)(ii)J.
Under Section 6 of FIFRA, registrants are required to submit any "additional factual
information regarding unreasonable adverse effects on the environment..." [§6(a)(2)j.
Failure to submit information required under this section is a violation of FIFRA
§12(a)(2)(B)(H).
• To knowingly falsify all or part of any application for registration, application for
experimental use permit, any records required to be maintained pursuant to FIFRA, any
report filed under FIFRA, or any information marked as confidential and submitted to
the Administrator under any provision of FIFRA [FIFRA §12(a)(2)(M)J.
• To falsify all or pan of any information relating to the testing of any pesticide (or any
ingredient, metabolite, or degradation product thereof), including the nature of any
protocol, procedure, substance, organism, or equipment used, observation made, or
conclusion or opinion formed, submitted to the Administrator, or that the person knows
will be furnished to the Administrator or will become pan of any records required to be
maintained by FEFRA [FIFRA §12(a)(2)(Q)].
• To submit to the Administrator data known to be false in support of a registration
[FIFRA §12(a)(2)(R)].
1-3 September 199J
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CHAPTER ONE
TABU 1-1. MAX* DIFFERENCES BETWEEN FTFRA AND TSCA GLP REGULATIONS
FIFRA
TSCA
SCOPE OF DATA SUBJECT To INSPECTIOK
40 CFR §160.1(a): "... studies that support
or are intended to support applications for
research or marketing permits for pesticide
products regulated by the EPA. This part is
intended to assure the quality and integrity of
data submitted pursuant to §§3, 4, 5, 8, 18,
and 24{c) of FIFRA and §§408 and 409 of the
FFDCA/
(b): "This part applies to any study ... of this
section which any person conducts, initiates,
or supports on or after 10/16/89."
40 CFR §792.1: "... studies relating to health
effects, environmental effects, and chemical fate
testing. This part is intended to assure the quality
and integrity of data submitted pursuant to testing
consent agreements and test rules issued under §4
of TSCA."
(b): "This part applies to any study ... of this
section which any person conducts, initiates, or
supports on or after 09/18/89."
(c): "It is EPA's policy that all data developed
under §5 of TSCA be in accordance with this
part. If data are not... EPA will consider such
data insufficient to evaluate the health and
environmental effects of the chemical substances
FIFRA
TSCA
RETENTION OF RECORDS
40 CFR §160.195: "... documentation
records, raw data, and specimens pertaining to
a study and required to be retained by this
part shall be retained in the archive(s) for
whichever of the following periods is longest:
(1) In the case of any study used to support
an application for a research or marketing
permit approved by EPA, the period during
which the sponsor holds any research or
marketing permit to which the study is
pertinent.
(2) A period of at least 5 yean following the
date on which the results of the study are
submitted to the EPA in support of an
application for a research or other marketing
permit.
(3) In other situations ... a period of at least
2 yean following the date on which the study
is completed, terminated, or discontinued."
40 CFR §792.195(bXl): "... documentation
records, raw data, and specimens pertaining to a
study and required to be retained by this part
shall be retained in the archives) for a period of
at least ten (10) years..."
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1-4
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INTRODCCTJON
FIFRA provides EPA with the authority to issue Notices of Warning for violations and to assess
administrative civil penalties of up to $5,000 per violation. Any person who knowingly violates FIFRA
may also incur criminal penalties of up to 550,000 or 1 year in jail. Falsification of submissions or
records may be the basis for a criminal referral under the United States Code, Chapter 47
(18 U.S.C. §1001). Actions may be taken against the registrant, the laboratory, or individuals for
falsifying the certification statements, records, or reports. Generally, EPA will examine the specific case
to determine who is most appropriately subject to an enforcement action.
In addition to enforcement actions taken under FIFRA, failure to comply with all applicable sections may
be used as the basis for rejection of studies. Where a study is not conducted in accordance with GLP
standards, EPA may refuse to consider the data as meeting regulatory requirements. GLP deviations may
also be the basis for the cancellation or suspension of a registration, modification of the research or
marketing permit, or denial of an application for such a permit.
1.4.2 TSCA Violations
Under TSCA, it is unlawful for any person:
• To fail or refuse to .comply with any rule promulgated or order issued under Section 4
of TSCA [TSCA §15(1)]
• To fail or refuse to (1) establish or maintain records; (2) submit reports, notices, or other
information; or (3) permit access to or copying of records, as required by TSCA or a
rule thereunder (TSCA §15(2)]
• To fail or refuse to permit entry or inspection as required by Section 11 of TSCA [TSCA
§15(4)].
TSCA allows EPA to assess civil and administrative penalties of up to $25,000 per violation per day.
Any person who knowingly violates any portion of TSCA may also be liable for criminal penalties of up
to 525,000 per violation per day and/or up- to 1 year in jail.
If the Administrator determines that a testing facility did not comply with any part of the GLP
regulations, data submitted may be determined to be unreliable for the purposes of showing that a
chemical substance or mixture does not present a risk of injury to health or the environment. If data
submitted to EPA to fulfill a testing consent agreement or a test rule issued under Section 4 of TSCA are
not developed in accordance with the applicable GLP regulations, EPA may require the sponsor of that
testing consent agreement or a test rule data submission to develop data in accordance with the GLP
standards before accepting those data [40 CFR § 792.17(c)]. In addition, it is EPA policy that all data
developed under Section 5 of TSCA be in accordance with GLP regulations. EPA considers any Section
5 data submitted that was not in accord with the GLP regulations to be insufficient to evaluate the health
and environmental effects of the chemical substance unless the submitter provides additional information
demonstrating that the data are reliable and adequate.
1-5 September 199J
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CHAPTER ONE
1.4.3 GLP Violations
EPA has developed several enforcement response policy (ERP) documents to guide case development
officers (CDOs) in determining the seriousness of GLP violations and the appropriate penalties to be
assessed for those violations. The FIFRA Enforcement Response Policy, dated July 2, 1990, contains
the EPA policy regarding penalty determinations for FIFRA violations. This ERP includes tables that
list the gravity levels for each violation of FIFRA and matrices for determining appropriate penalty
amounts based on the gravity, size of business, history of noncompliance, culpability of the violator, and
harm to human health or the environment. The ERP applies to any violations of FIFRA, including those
concerning GLP regulations. Specific FIFRA charges given in the ERP are in reference to Section
12(a)(2)(M), for knowing falsification of reports submitted to EPA; Section 12(a)(2)(Q), for falsifying
information related to testing; and Section 12(a)(2)(R), for submission of data known to be false.
The FIFRA ERP addresses GLP violations in the following manner: a high-level GLP violation has a
maximum civil penalty of $5,000 per violation; a middle-level GLP violation has a maximum civil penalty
of $4,000 per violation; and a low-level GLP violation has a maximum civil penalty of $3,000 per
violation.
The GLP ERP supplement to the FIFRA ERP was released on September 30, 1991. This document
provides guidance regarding certain enforcement policy issues, including multiple GLP violations and
liability for GLP violations. It also provides guidance regarding which violations are considered to be
high-, middle-, or low-level violations.
EPA developed an ERP for TSCA GLPs in 1985. The TSCA ERP outlines both the levels of action, and
the penalty amounts that can be imposed where violations have been discovered. The TSCA ERP for
GLPs is applicable to those studies used to obtain data for TSCA section 4 hazard evaluations, TSCA
section 5 data submissions, and negotiated testing agreements. The TSCA ERP identifies four response
levels for GLP violations, including:
Notice of Noncompliance (NONs) - NONs are the most common response to a TSCA
GLP violation. They are used for minor, technical or form violations. They are not
used for a substantive violation, or for any repeat offenses under TSCA section 4.
Civil Administrative Penalties CCAPs) - CAPs are appropriate when one or more
violations, considered together or separately, have the potential to affect the reliability
and accuracy of the data.
Criminal Sanctions - Criminal sanctions are used in serious cases of misconduct. The
factors used to determine whether or not to. proceed with a criminal prosecution include
whether there was "guilty knowledge" or intent on the part of the responsible party, or
where violations are "knowingly or willfully" committed (i.e., falsifying material data.
intentional concealment of results through omission or selective reporting).
GLP Inspection Manual 1-6
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INTRODUCTION
• Study Invalidation - Under 40 CFR 792.17, EPA may determine that the submitted data
was not collected in accordance with the applicable GLPs and may be unreliable for the
purposes of indicating that the chemical in question is not expected to pose an
unreasonable risk to human health or the environment. If the data is submitted as part
of a TSCA section 4 study, EPA may require a new study to be conducted. For studies
submitted under §5 or a negotiated testing agreement that do not conform to GLPs, EPA
may consider the data insufficient to permit a reasoned evaluation of the environmental
and health effects of a chemical substance.
Similar to the FIFRA GLP ERP, a penalty matrix was created to aid CDOs in determining the amount
of fines to be leveled for CAPs. The ERP also delineates adjusting factors that may be taken into
consideration when determining the appropriate response level to the GLP violation.
Inspectors are encouraged to review the FIFRA and TSCA GLP ERPs to familiarize themselves with the
types and levels of GLP violations EPA has established.
1.5 STANDARDS OF PROFESSIONAL CONDUCT
Through many years of inspection experience, EPA has developed procedures and requirements that
assure ethical action on the part of its inspectors. These ethics have been established to protect the
individual, the Agency, and industry as well. Because inspectors act as officers of the United States
Government, they should perform their duties with the highest degree of honesty and integrity. In
addition, they are expected to conduct themselves in a manner that will reflect favorably on themselves
and the Agency. As such, the following rules of ethics should be adhered to at all times:
• AJ1 investigations shall be conducted within the framework of the United States
Constitution and with due consideration for individual rights, regardless of race, sex,
creed, or national origin.
• The inspector shall uphold the Constitution, laws, and regulations of the United States
and all governments therein and never be a parry to their evasion.
• The inspector shall never use any information obtained confidentially in the performance
of governmental duties as a means for making a private profit.
• Any act (or failure to act) that might be construed as being motivated by personal or
private gain (conflict of interest) should be avoided.
• The inspector shall never discriminate by dispensing special favors or privileges to
anyone, whether for remuneration or not; and never accept, for him/herself or his/her
family, favors or benefits under any circumstances.
• Facts of an investigation are to be developed and reported completely, objectively, and
accurately.
1-7 September 1993
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CHAPTER ONE
The inspector shall make no promises of any kind; government employees cannot bind
government enforcement.
The inspector shall continually attempt to improve professional knowledge and technical
skill in the investigative field.
CLP Inspection Manual
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PKOCEDUKZS
2.0 PRE-INSPECTION PROCEDURES
2.1 INTRODUCTION
This chapter contains guidance on conducting pre-inspection activities pertaining to FIFRA and TSCA
GLP inspections. A good inspection begins with planning, which should commence well before the
inspector visits the subject facility. Planning is the process during which the inspector identifies all the
required activities to be completed during the inspection process. These activities include obtaining
records before the inspection, conducting the inspection, follow up, and writing the inspection report.
This chapter describes the planning process that should take place prior to any GLP inspection. The basic
elements of inspection planning are determining the scope of the inspection (Section 2.2); inspection
planning (Section 2.3); reviewing EPA information-(Section 2.4); providing advance notification of the
inspection to the facility (Section 2.5); coordinating the inspection team (Section 2.6); and gathering
inspection documents and equipment (Section 2.7). Section 2.8 discusses Confidential Business
Information (CBI) issues.
2.2 DETERMINING THE SCOPE OP THE INSPECTION
The first step in the inspection planning process is determining what type of inspection will be conducted.
GLP inspections usually involve both a compliance review and one or more study audits. In some cases,
only a study audit will be conducted.
2.2.1 Compliance Reviews
A compliance review is used to obtain a "snapshot in time" at a testing facility (i.e., to determine
compliance status at the time the inspection takes place). During a compliance review, the inspection
team may identify an ongoing or recently submitted study and evaluate to what extent the study is being
conducted in accordance with GLP regulations. Practices evaluated may include any of the items or
activities required in the GLP regulations such as use and maintenance of SOPs, data recording, handling
of test systems, or other operations. A detailed discussion of all elements of a compliance review is
presented in Chapter 4.
2.2.2 Study Audits
The purpose of a study audit is to determine whether the testing facility being inspected has documented
the raw data necessary to support conclusions previously submitted to EPA and whether the GLP
Standards were followed. During a study audit, auditors conduct an overall review of raw data, verify
the accuracy of the data, and examine the submitted study report to determine whether the data were
collected following the proper procedures required by the GLP regulations. A discussion of the aspects
of study audits is presented in Chapter 5 and in the relevant SOPs.
September
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COAfTEX TWO
2.3 INSPECTION PLANNING
Planning includes conducting a thorough review, prior to the inspection, of EPA records and other
information pertaining to the facility to be inspected. This will save time because familiarity with the
operation, history, and compliance status of the subject facility decreases the need for more extensive
discussion of these areas during the limited time typically allotted to an onsite visit. In addition, planning
promotes a better relationship with the regulated community because the inspector will be better able to
answer questions concerning the application of GLP requirements to a particular type of facility.
Proper planning also enhances the facility personnel's confidence in the EPA. inspector and aids in
establishing good relationships with facility representatives. An inspector that knows what s/he wants,
how to proceed, what to accomplish, and who articulates such goals to the facility personnel will appear
well organized and in control. Such an appearance indicates to the facility personnel that the inspector
is a professional and is concerned not only with using his/her own time effectively, but also the time,
energy, and resources of the facility as well.
Another benefit of planning is that it enhances the inspector's ability to identify and document potential
violations and thus provide more time to collect necessary data to assist CDOs in their subsequent
compliance and enforcement activities. Planning an inspection will result in a more efficient and
productive inspection overall.
The objectives of inspection planning are to:
• Understand the objectives of the inspection.
• Understand applicable GLP regulations.
• Be well-versed in the policies and procedures governing GLP'inspections and the SOPs
of the Laboratory Data Integrity Assurance Division (LDIAD).
• Obtain the proper equipment, material, and documents and/or forms for conducting the
inspection.
• Be prepared to collect and record documentary, and if necessary, nondocumentary
samples.
Once a facility has been selected for inspection, proper planning should assure the following:
• A properly focused inspection
• A systematic framework for comparing a facility's operating practices against applicable
GLP regulations
GLP Inspection Manual 2-2
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PXOCEDUKZS
• Use of the most efficient and effective approach for conducting the inspection, given the
available personnel and funding
• Gearly established task assignments in the field for each member of the inspection team.
2.4 REVIEWING EPA INFORMATION
The inspector's responsibilities are initiated by the receipt of the Investigation Request letter from the
Director, LDIAD. For a study audit, copies of all study reports to be audited will be forwarded by the
Scientific Support Branch (SSB) to the inspector and also to the auditor(s) when appropriate in a timely
fashion (ideally at least 4 weeks prior to the start of the inspection). Members of the audit team will be
provided with copies of pertinent study reports at the same time. The inspector should request any
additional information that s/he will find useful in preparing for the inspection from a variety of Regional
and Headquarters personnel. Such information may include (but is not limited to):
• Copies of previous inspection report(s)
• General facility information
• Correspondence with facility personnel
• Discussion with appropriate program staff, such as the Office of Pesticide Programs
(OPP) reviewers
• Available study review documents from OPP or the Office of Pollution Prevention and
Toxics (OPPT)
• Relevant program documents, such as FIFRA guidelines or TSCA test rules, and the
SOPs of LDIAD.
2.5 PROVHMNO ADVANCE NOTIFICATION
EPA is not required by law to provide advance notice of an inspection. However, OCM has adopted a
policy of providing such notification, based on the circumstances of the particular inspection and facility.
It is up to the discretion of the SSB Branch Chief to decide whether to provide advance notification.
Because of the highly technical nature of these inspections, the sensitivity of the information involved,
and the need to assure that appropriate personnel and records are available for inspection, the testing
facility, in most cases, is notified in advance that an inspection is planned. (For inspections involving
certain well-documented complaints or tips, prior notification may not be given.)
Approximately 2 weeks before the scheduled inspection, the Chief of SSB (or another designated person)
will contact the responsible management official at the facility and notify that person of the scheduled
inspection. The initial telephone notification will be confirmed .by a notification letter (see Appendix A).
2-3 September 1993
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CHATTER Two
The inspector will receive a copy of the notification letter. At the same time, the inspector will receive
an investigation request (see Appendix B), which gives the name and telephone number of the facility
contact person and of each inspection team member. This request also will provide other information
necessary to the planning and conduct of the inspection.
Once the facility has been notified by SSB that an inspection will be conducted, the primary responsibility
for the conduct of the inspection passes to the inspector. Any further communications with the facility
personnel should be made by the inspector. The inspector should keep SSB and supervisory personnel
apprised of the status of the inspection and should consult with them on any substantive issues that may
arise or changes that may be required.
The potential advantages and disadvantages associated with providing advance notification are as follows:
• Potential advantages
The facility will have the necessary documents, records, or personnel available
for the inspector, saving valuable time on site and requiring less time during
followup stages of the inspection.
The facility personnel appreciate advance notification so that their regular
operations are not interrupted, thereby fostering a cooperative relationship with
EPA.
• Potential disadvantages
The inspector may not have the opportunity to view the facility under normal
operating conditions because facility personnel, with advance notification, could
tailor operations to fit preconceived notions of what the inspector may want to
see.
At a facility suspected of violating GLP requirement(s), the company officials
might conceal, alter, or destroy evidence confirming the violation(s) after
receiving advance notification.
2.5.1 Items Addressed in Advance Notification
If advance notification is provided, the inspector should make note of it in the inspection report. Specific
objectives of advance notification include the following:
• Identifying the inspector
• Scheduling the inspection (including establishing time of arrival)
• Obtaining verbal agreement to allow the inspection team to enter
CLP Inspection Manual 2-4
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• Determining the appropriate site(s) for the inspection, including identifying the location
of necessary records, as specified in the inspection plan
• Ensuring that personnel are available to accompany EPA inspectors during the inspection
• Ensuring that someone onsite will be able to make claims of HFRA/TSCA CBI
• Encouraging the facility and sponsor to have all records transferred to the inspection site
before the inspection
• Obtaining directions to the facility
• Discussing problems, concerns, or questions relative to the inspection or studies to be
audited or any other issues
• Ensuring there is photocopying capability and, if not, what document reproduction
options are available to the inspection team.
When the facility has not previously been inspected for GLP standards compliance, the inspector should
be certain that facility personnel are aware of what is involved in such an inspection, what records should
be made available, what personnel should be present, etc. If the facility representative contacted does
not cooperate, the inspector's supervisor and the Chief, SSB at EPA Headquarters should be consulted
for instructions on how to proceed.
2.6 INSPECTION TEAM COORDINATION
As soon as the identity of the inspection team is known, the inspector should contact each person and
begin planning the conduct of the inspection. As early as possible the inspector should:
Coordinate travel plans, including the hotel to be used by the team, times of arrival of
team members, means of transfer from the airport to the hotel, and provision for one or
more rental can of suitable size to accommodate the team.
Ascertain that each team member is aware of the dates of the inspection, especially the
date and time that s/he will be required to be available for a pre-inspection team meeting.
and the expected date and time for the conclusion of the inspection. Assure that each
team member is aware of the proper attire for the inspection and that has been briefed
on appropriate safety procedures. The inspector should not underestimate the time
needed to conduct the inspection.
Confirm that those individuals who will be conducting the study audit, portion of the
inspection are aware of die studies (or portions of studies) to be audited. This is
especially important for large or complex studies where more than one auditor will be
reviewing data. If an auditor will be expected to assist with portions of the GLP
compliance review of the facility, the inspector should discuss this with him/her during
2-5 September 19<5.»
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CHATTER Two ^^^^
these early planning stages. Each member of the inspection team should be aware of
his/her responsibilities during the compliance review and/or audit.
The inspector should also arrange to provide copies of applicable LDIAD SOPs to auditors who do not
already have these documents. In addition, the inspector may need to assure that the inspection team is
aware of proper procedures for receiving and handling CBI, especially as related to inspections conducted
under TSCA. (TSCA CBI requirements are more stringent than those found under FIFRA, and the
procedures for handling CBI under TSCA are more complicated.) The inspector may also need to
coordinate with representatives of the EPA Regional offices, FDA, State agencies, contract organizations,
or foreign governments. S/he should determine the level of experience of each auditor in conducting
compliance reviews and/or study audits for studies conducted under GLP regulations. The inspector may
need to provide guidance to less experienced auditors, both before and during the inspection.
2.6.1 Inspection Plan
Prior to the inspection, the inspector should prepare a plan for the inspection. S/he should remain
flexible about this plan, since circumstances encountered at the facility may require last-minute changes.
However, these can usually be minimized by adequate pre-inspection communication with SSB, the team
members, and facility personnel. The inspection plan should include details such as date and time for
the pre-inspection meeting with t«»" members, date and time of arrival at the facility, name of facility
contact person, assignment of responsibilities for GLP compliance review and study audits, and proposed
timetable for accomplishing the compliance review and/or study audits. The inspector should assure that,
if necessary, team members are cleared to handle FIFRA or TSCA CBI.
•
2.6.2 Pre-inspection Meeting with Team Members
The pre-inspection meeting between the inspector and the team members usually occurs once the team
has assembled just prior to the start of the inspection. The meeting provides an opportunity for the team
members to get acquainted with each other and to attend to any last-minute details. It allows the inspector
to verify that each team member is aware of his/her assignments and responsibilities and that each
member understands the principles of adequate documentation and evidence gathering. During the
meeting, the inspector should discuss the schedule and format for report preparation and assure that each
team member has copies of the LDIAD SOPs for report preparation.
2.6.3 Preparation foe Audits
The study auditors) also need adequate preparation. As early as possible in the audit planning, the
auditor should receive and review the study(ies) to be audited to become familiar with the technical.
management, and GLP aspects of the study. The auditor should also review the applicable GLP standards
and the test rule or FIFRA guidelines for the study to be audited. During this review, discrepancies.
GLP Inspection Manual 2-6
-------
deficiencies, and potential problem areas can often be identified and a plan developed for approaching
the audit. The auditor may develop a number of questions to be discussed with study personnel.
The auditing preparation is, in part, used to determine if the studies were required to have been conducted
in accordance with the GLP regulations. Often the inspector will ask the auditor to make that
determination, particularly in those areas directly involving the auditor's field of expertise. If not already
familiar with the FIFRA and TSCA GLP regulations (40 CFR Parts 160 and 792, respectively), the
auditor should review these regulations and discuss any questions with the inspector.
Prior to the inspection, the auditor should review all pertinent LDIAD SOPs for conducting study audit(s)
of the specific study types. These documents provide guidance and a standard procedure for conducting
the various aspects of the GLP inspection. (For a complete index of SOPs, See Section 5.6.)
The auditor should always discuss any uncertainties about an upcoming inspection with the inspector.
The inspector should make it clear that any problems encountered during the audit should be brought to
the inspector's attention. The auditor should not confront facility personnel over any outstanding issues.
2.7 GATHERING INSPECTION DOCUMENTS AND EQUIPMENT
In addition to preparing the written inspection plan and reviewing EPA records prior to conducting the
inspection, the inspector should gamer and prepare the necessary documents and equipment to be used
during the inspection.
2.7.1 Types of Documents
No single list of documents and equipment can be appropriate for all inspections. The list provided below
is intended for guidance purposes only. The inspector's experience in the field and information obtained
during pre-inspection planning should assist in preparing lists tailored to specific inspection sites and
needs. Specific needs will be determined by the requirements of the inspection, the availability of
equipment, conditions at the facility, OCM policies, and whether advance notification of an inspection
has been given. Documents necessary for the inspection should be prepared in advance of the inspection
whenever possible. '
The inspector should obtain copies of the inspection forms that are needed for the inspection. Several
spare copies of each form should always be carried. FIFRA GLP inspections require:
• FIFRA Notice of Inspection [EPA Form 3540-2]
• FTFRA Receipt for Samples [EPA Form 3540-3].
Forms needed for a TSCA GLP inspection include:
2-7 September 1993
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CHAfTEX TWO
• TSCA Notice of Inspection [EPA Form 7740-3]
• TSCA Inspection Confidentiality Notice [EPA Form 7740-4]
• TSCA Receipt for Samples and Documents [EPA Form 7740-1]
• TSCA Declaration of Confidential Business Information [EPA Form 7740-2].
In addition, the inspector should be certain to take the following documents and materials on an
inspection:
• Copies of FIFRA. TSCA. and the appliqable regulations. Inspectors shouJd have copies
of FIFRA and TSCA and the applicable regulations with the preamble available upon
request. Having such documents available for distribution may help improve the
relationship between EPA and the regulated community, which can foster better facility
compliance.
• EPA outreach materials. Inspectors should provide current, relevant educational,
guidance information to facility officials upon request or as deemed appropriate by the
inspector.
• Administrative information. When on travel, the inspector should take travel
authorizations and telephone numbers of travel and procurement personnel who may need
to be contacted.
Additional documents could include:
• Q & A documents and GLP Regulatory Advisories
• LDIAD Standard Operating Procedures
• Any related Federal Register notices.
The inspector shouJd also obtain enough bound field notebooks for each team member, although often
the auditors will bring their own notebooks for the inspection. The inspector should assure that loose-leaf
or spiral notebooks, or pads of paper are not used. (This prevents anyone from tampering with the
notebook, and removes any doubt about the contents of the notebook should it be submitted as evidence
in court.) EPA policy is to use only bound notebooks on inspections. However, some inspectors may
use a checklist as part of the inspection documentation. If a checklist is used on a GLP inspection, the
inspector must (1) reference the checklist with a number or alphanumeric identifier (unique to that
inspection) in the bound field notebook and on the checklist and (2) record the date, name of laboratory..
and inspector's initials on each page of the checklist.
Appended to this manual are two checklists developed for use on a GLP compliance inspection (Appendix
D and E). These checklists are provided as tools for the inspector and their use is entirely optional
Inspectors using these, or any checklist, are reminded that a checklist is only a guide, and shouJd in no
way limit the scope of any inspection or investigation.
GLP Inspection Manual 2-8
-------
On occasion, more than one inspection will be conducted at a facility during the same time period (e.g.,
separate FIFRA and TSCA GLP inspections or inspections at two or more testing facility organizational
sub-units within the facility, such as toxicology and chemistry). In this event, separate sets of documents
may be required for each inspection, and separate notebooks may be required for each inspection. The
inspector should bear this in mind when assembling the inspection supplies.
2.7.2 Inspection Equipment
The types of equipment that an inspector takes to an inspection site will vary depending upon the nature
and extent of the inspection and the type of testing facility to be inspected. The inspector should use
her/his best judgment, based on training and inspection experience and on knowledge gained in preparing
for the inspection, in determining what equipment is necessary for a particular inspection. The equipment
should be well-maintained and in good condition at the time of the inspection. Therefore, prior to each
inspection, the inspector should check the equipment to make sure that it is in good working condition.
Since each inspection is unique, no single list of equipment or forms can be devised that will fit every
inspection situation. The types of equipment most likely to be needed during a GLP inspection are
summarized in Table 2-1.
2.8 Confidential Business Information Considerations
2.8.1 TSCA
Section 14 of TSCA and EPA regulations (40 CFR Part 2) protect CBI from disclosure. CBI includes
trade secrets (including process, formulation, or production data), the uncontrolled disclosure of which
could cause damage to a facility's competitive position. In general, disclosure of CBI is prohibited;
however, there are certain specific and limited exceptions' (see 40 CFR Part 2). EPA's Office of General
Counsel is responsible for making the final administrative determination as to a CBI claim.
An inspector must notify facility representatives of their right to claim data at the facility as CBI. Because
the inspector may require access to CBI before (i.e., while preparing for an inspection), during, and after
an inspection, the inspector must be knowledgeable of EPA procedures governing access to, handling of,
and disclosure of CBI. The inspector and others who may use the information must have TSCA CBI
access authorization, since only authorized individuals may have access to CBI. An inspector may need
access to CBI data that a subject facility submitted to EPA or provides during the inspection, as well as
information that was collected during a prior inspection.
A CBI-cleared inspector can obtain access to CBI documents at EPA by requesting the information from
an appropriate Document Control Officer (DCO). The DCQ is responsible for the following:
2-9 Septembtr 1993
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COAfTEX TWO
TABLE 2-1. TYPES OF EQUIPMENT
• Camera
• Pocket calculator
• Clipboard
• Locking briefcase
• Stamp pad
• Plastic covers
• Disposable towels or rags
• Portable typewriter
• Bound notebooks
• Flashlight and batteries
• Pens
• Blank pad
• Attendance sheets for opening
and closing conference
• Relevant guidelines (FIFRA) or
test rule (TSCA)
• Pre-addressed envelopes
(e.g., to Document Control Officer)
Film and flash equipment
Tape measure
Waterproof pens, pencils, and markers
"Confidential Business Information" stamp
Plain envelopes
Polyethylene bags
Portable copying machine
Pocket knife
-. Computer
Sampling material
Pencil
Highlighters, multicolored
Bound notebooks
Post Its
Study reports
Inspection history
Regulations
GLP PROGRAM MATERIALS
Safety glasses or goggles
Face shield
Ear plugs
Rubber-soled, metal-toed, nonskid shoes
Liquid-proof gloves (disposable, if possible)
Coveralls, long-sleeved
Hard hat
Plastic shoe covers, disposable
Respirators and cartridges
Self-contained breathing apparatus
Notification letter
Inspector credentials
Letter credentials for noncredentialed team
members
Investigation request
Notice of Inspection, FIFRA or TSCA
Receipt for Samples, FIFRA or TSCA
CBI forms, TSCA
SOPs
Directions/maps •
Checklist(s)
'in accordance with EPA policy, an inspector may not do field work without first completing an approved health and
safety training program. Penonnel who uie respiratory protection equipment must also complete ipecialized training, which
include* training on protective equipment selection criteria. Program-specific safety training has been developed for field
personnel facing particular riiki. •
CLP Inspection Manual
2-10
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• Verifying that the requesting inspector is on the authorized CBI access list
• Providing a copy of the CBI classified document to the inspector
• Determining whether the inspector has secure storage approved by EPA if the inspector
is to keep the CBI for more than a day.
It is very possible that most data obtained from EPA Headquarters is CBI. To facilitate the transfer of
CBI to the Regions or National Enforcement Investigations Center (NEIC) for use in conducting TSCA
GLP inspections, EPA established a policy authorizing telephone discussion of CBI information obtained
by EPA. Basically, communication by telephone can include CBI when the contact is from Region to
Region, Region to specified Headquarters offices, Headquarters to Region, Headquarters or Region to
subject facility, or Headquarters to NEIC.
Whether or not it is anticipated that CBI documents will be collected during a TSCA GLP inspection, the
inspector must provide a TSCA Inspection Confidentiality Notice to the .responsible facility official at the
beginning of the inspection. This form is used to inform facility officials of their right to claim part of
the inspection data as CBI. The inspector should be familiar with the procedures for asserting a CBI
claim and the four criteria which the claimed information must meet. These four criteria are discussed
in detail on the TSCA Inspection Confidentiality Notice.
If documents are collected for which facility officials exercise their right to claim confidentiality, the
inspector must list all such documents on the TSCA Declaration of Confidential Business Information.
The inspector must take custody of all CBI documents before leaving the facility and must maintain them
in his/her custody, using all proper procedures and safeguards, until they can be received by a DCO.
The DCO will then properly transfer such documents as needed to the auditors or the inspector.
2.8.2 FIFRA
If a facility claims that certain business information is confidential under FIFRA, the inspectors must
follow procedures for handling FIFRA sensitive information (e.g., CBI, trade secrets) found in the
FIFRA Information Security Manual (July 1988).
In general, during an inspection, representatives of a facility inspected under FIFRA must be informed
of their right to claim any information as CBI. In the event that documents are collected for which
facility officials exercise their right to claim confidentiality, the inspector must identify all such documents
(and samples) on the FIFRA Receipt for Samples as confidential. The inspector must take Custody of all
CBI documents before leaving the facility and must maintain them in his/her custody, using all proper
procedures and safeguards, until they can be received by a DCO. The DCO will then properly transfer
such documents as needed to the auditors or the inspector.
2-11 September
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CHAfTEK TWO
BLANK PAGE
CLP Inspection Manual 2-12
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3.0 INSPECTION PROCEDURES
3.1 INTIOOOCDON
This chapter discusses the required procedures for entering a testing facility to conduct a GLP inspection
under FEFRA and TSCA. This chapter also presents the statutory requirements, and OCM policies
applicable to GLP inspections. Guidance is provided to the inspector on the preliminary aspects of a GLP
inspection, ranging from a discussion of the importance of obtaining testing facility owner/operator
consent for the inspection to a listing of procedures for conducting the opening and closing conferences.
Procedures for determining compliance with various sections of the GLP regulations are covered in
succeeding chapters and reference SOPs.
3.2 INSPECTION AUTHORITY
An inspection may be conducted only after the inspector has presented the following items to the owner,
operator, or agent in charge:
• Appropriate credentials
• Written Notice of Inspection.
Inspections must be conducted in me following manner:
• Initiated and completed in a timely manner
• Conducted at reasonable times, within reasonable limits, and in a reasonable manner.
3.2.1 Credentials
Section 8 of FTFRA and Section 11 of TSCA require the EPA Administrator or any duly designated
representative of the Administrator who conducts an inspection of a testing facility to present the owner,
operator, or agent in charge with appropriate credentials and with a written Notice of Inspection
(discussed in Section 3.2.2). Credentials are issued by the EPA Administrator or her/his designee and
the inspection OMf t» made only upon presentation of such credentials. The credentials are identifying
papers that sqji£ the holder of the papers (i.e., the inspector) is authorized to conduct official
'*«:•••-
investigations aaff inspections pursuant to all laws (including GLP inspections) that EPA administers.
Inspectors most present credentials whether or not testing facility officials request identification. Once
testing facility officials have viewed the credentials, they may wish to telephone EPA Headquarters or
the Regional Office to verify the inspector's identification, which is permissible. However, credentials
may not be photocopied. Credentials should also be readily available so that they can be presented to
other facility representatives during the course of the inspection. Lastly, the inspector should make a note
in her/his Meld log that credentials were presented.
3-1 September 1993
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CHAPTER THREE
EPA employees who do not have EPA inspector credentials, but who accompany the inspector and have
a role on the inspection team, such as a data auditor, should be prepared to present their EPA badges or
another form of identification (if not an EPA employee) plus a letter of authorization specific to the
inspection being conducted. The issuance of such letters for sensitive inspections is merely an additional
precaution and does not diminish the authority of an inspector to utilize any appropriate EPA employee
as part of an inspection team. The inspector should arrange for and have available letters of introduction
and authorization for any members of the inspection team who are not EPA employees.
3.2.2 Written Notice of Inspection
As soon as the inspector has identified herself/himself and presented the required credentials, s/he must
present to the owner, operator, or agent in charge of the testing facility with a written notice of "the
premises or conveyances to be inspected." This Notice of Inspection (see Figure 3-1 for the TSCA
Notice of Inspection and Figure 3-2 for the FIFRA Notice of Inspection") informs the owner, operator,
or agent in charge of the reason for an inspection under Section 8 of FIFRA or Section 11 of TSCA and
contains the inspector's address and signature. Although the time of the intended inspection is not
required, the scheduled time (and date) of the inspection should be included in the Notice of Inspection
to establish that the inspection was requested at a reasonable time, as required by Section 8 of FIFRA
and Section 11 of TSCA.
The inspector is required to present the Notice of Inspection after arrival at the testing facility. A
separate inspection notice must be presented for each inspection, but a separate notice is not required for
each entry made during the period covered by the inspection (e.g., for each separate day of a multi-day
inspection). The inspector should make a note in the inspection notebook that the Notice of Inspection
was presented and should include a copy in the inspection report.
3.3 PRELIMINARY STEPS FOR CONDUCTING A GLP INSPECTION
The inspector should use the following procedures to assure compliance with statutory requirements and
OCM policy covering GLP inspections:
• To comply with the statutory requirement that the inspection of a testing facility subject
to GLP regulations be conducted at a reasonable time, the inspector should inspect the
testing facility only during normal working hours, unless mitigating circumstances
required mat an inspection be conducted during nonbusiness hours. For example, it may
be preferable to enter a testing facility that operates on a shift basis during one of the off-
hour shifts. Similarly, it may be preferable to start the inspection of a field site early in
the morning.
• The inspector should arrive at the testing facility at the time designated (if it has been
included) in the Letter of Advance Notification. GLP regulations do not require that the
written Notice of Inspection include the time of the inspection, but the inspector may
want to include the time on the Notice of Inspection as documentation.
GLP Inspection Manual 3-2
-------
INSPECTION PROCZDCRZS
FIGURE 3-1.
TSCA NOTICE OF INSPECTION
&EPA
DATE | INSPECTOR NO. OAlLr S
WASHINGTON, OC 2O*40 • Far** uj-giij
TOXIC StIKTANCM CO*T«OL ACT °*?~£ "/m "t-ll-li
NOTICE OF INSPECTION
2. TIME 3. FIRM NAM£
SO. NO.
REASON FOR INSPECTION
Under the authority.of Section 1 1 of the Toxic Substances Control Act :
CZ For the purpose of inspecting (including taking samples, photographs, statements, and other inspection activities! an tstaoiisn-
ment. facility, or other premises in wmch chemical substances or mixtures or articles containing same are manufactured, proc-
essed or stored, or held before or after their distribution in commerce (including record!, files, papers, processes, controls, and
facilities) and any conveyance being used to transport chemical substances, mixtures, or articles containing same in connection
with their distribution in commerce (including records, files, papers, processes, controls, and facilities! bearing on whether the
reduirementj of the Act applicable to the chemical substances, mixtures, or articles within or associated with such premises or
conveyance have eeen complied with.
UJ In addition, this inspection extends to /Oitck Appropriate blocktl:
O A. Financial data
Cj 3. SeJes data
G C Pricing data
Q 0. Personnel data
D E. Research data
The nature and extent of inspection of such data specified in A through £ above is as follows;
TTTCT J
C»A *«mt 77404 I12-C3)
RfCI'IfNT 3IGMATUKI
ATI SIGNgO nrtS 3ATI JIGNIO
•u.i. xvtuwur >i,-n:x :rr::i. •,!)..,..„, IN9ICTIOM HLl
3-3
Septembtr 1993
-------
CHASTEK
FIGURE 3-2.
FIFRA NOTICE OF INSPECTION
U. S. ENVINONMf NTAk ^MOTf CTION ACINCY
NOTICE OF INSPECTION
AOORUS ,CfA Atrvxutf Offtai
NAMC 0^ INDIVIDUAL
TITLI
FINM KAMI
PldM AOOMCSS lHnmb*r. Sftn, Oty. Stra via Zlf Codt>
SIGNATURI Of «f A (MTt.OVII
TITLf
«tA5ON
'OK TMC *UI»OSC Of INS»CCTIMC AMD OIT*iMfN« JA-»LtJ.O' »MY •IJTlCIOtl OK OCVICCS PACKAGCO. LAttWeO. i «m«nd«d ft U.S.C. US tt
quoted on th* r*v«r«* of thti form.
POT. ]J4«4 (In. 1-77)
• •CV1OUS COITIOM MAT ftc UIKO
UMTIV. »u«l_r » (XHAUfTtO
nw- IITAILllHMf NT CO»V
i- SAMPLI KICOMO corv
1- MOIOM
3- i
CL? Inspection Manual
3-4
-------
• The inspector should enter the testing facility through the main entrance. If SSB sent an
advance letter (or notice) of inspection to the testing facility and in response the testing
facility designated a different entrance, the inspector should use the designated entrance.
• Upon arrival at the testing facility, the inspector should identify him/herself to the guard
or receptionist, as necessary. FIFRA and TSCA require only that credentials be presented
to the "owner, operator, or agent in charge," but the inspector may present them to others
as a courtesy or to expedite entry. Inspector credentials should be kept accessible
throughout the inspection. Business cards, EPA identification cards, and EPA badges do
not constitute credentials but may be used for introductory purposes as appropriate.
• The inspector should aslc the guard (or the secretary or receptionist, as appropriate) to see
the testing facility owner, operator, or agent in charge.
• The inspector may sign a visitor's log or register if requested to do so. However, the
inspector may not sign any such sheet or other document if it contains restrictive language
limiting the scope of the inspection, the manner in which the inspection may be
conducted, or the manner in which information may be used (e.g., a waiver, release of
liability, restriction on the use of photographic or other recording devices). Attempts to
restrict the inspection are discussed in detail in Section 3.4.3.
• Once the owner, operator, or agent in charge has been located, the inspector must present
the testing facility official with proper inspector credentials and the FIFRA and/or TSCA
Notice of Inspection. The inspector must assure that the person to whom the credentials
are presented is the authorized facility representative. If the person greeting the
inspection team is not the same individual who communicated with the inspector during
the pre-inspection preparation (if such communication occurred), the inspector should
verbally determine that this person is authorized to grant entry and allow the inspection
to proceed. The verbal acknowledgement of responsibility on the part of the facility
representative should be noted in the inspector's field notebook.
• EPA policy requires the GLP inspector to obtain consent from the testing facility owner,
operator, or agent in charge prior to entering a testing facility to conduct an inspection.
To document consent in the case of a FIFRA inspection, the inspector should record the
name and title of the person giving consent and the date and time consent was given in
the field notebook. In the case of a TSCA inspection, the facility representative must sign
the TSCA Notice of Inspection form. If an inspector is denied entry to a testing facility
to conduct a GLP inspection, or if the testing facility owner, operator, or agent in charge
attempts to impose conditions upon the entry (i.e., conditional entry), the inspector should
follow the actions described in Section 3.4.3.
3.4 CONSENT To ENTER AND INSPECT
3.4.1 Procedures to Gain Consent
EPA procedure calls for the inspector to obtain consent for the inspection. Therefore, the inspector
should not conduct an inspection until s/he has accomplished one of the following tasks:
3-5 September 199}
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CHAPTER TBRZB __
• Obtained consent prior to conducting the inspection and/or
• If unable to obtain consent, followed proper procedures governing what should be done
when entry to a testing facility is denied or when conditions or restrictions are imposed
by testing facility officials upon authorized GLP inspectors (see Sections 3.5 and 3.4.3,
respectively).
Consent to enter must be given knowingly and freely. The inspector must not coerce or lie to testing
facility officials to induce consent. For example, the inspector must not suggest that failure to permit
entry may result in the imposition of civil or criminal penalties, since the entry may then be considered
nonconsensual (i.e., because of the "threat" of negative consequences).
Consent must be given by the person in possession (i.e., the owner or operator) of the premises, or by
some other person with authority to give consent at the time of the inspection. An owner does not always
have possession, and so may not be authorized to give consent; for example, the owner may be renting
the property to a tenant who is on the property. If someone in possession of the testing.facility cannot
be located, the inspector must make a good faith effort to determine who may otherwise consent to the
entry (i.e., the agent in charge). The inspector should present her/his credentials to that individual and
record the name and title of that person in the field notebook.
The GLP inspector must obtain consent to enter the premises for each noncredentialed person (e.g., study
auditor. Senior Environmental Executives (SEEs), observer, or contractor) who intends to accompany the
inspector on an inspection. If consent is not given, these persons may not enter the premises to be
inspected. However, refusal to allow an inspection team member access to the facility is considered
conditional consent. No uncredentialed person may have access to TSCA CBI unless s/he has been
authorized for CBI access by the Information Management Division (IMD) of the Office of Pollution
Prevention and Toxics (OPPT). IMD circulates monthly a list of persons with TSCA CBI clearance to
the Regional and program DCOs.
In most instances, if the inspector follows proper procedures upon arrival at the testing facility (i.e.,
presentation of credentials and Notice of Inspection), obtaining consent to enter will be simple. However,
special situations may arise:
• Owner or operator reluctance to give consent
• Conditional consent
• Withdrawal of consent.
These situations and the inspector's responsibilities in each situation are discussed below.
CLP Inspection Manual 3-6
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PXOCEDUXSS
3.4.2 Reluctance to Give Consent
The receptiveness of testing facility officials toward an inspector may vary from facility to facility. If
consent to enter a testing facility is denied outright, the inspector should follow the procedures governing
denial of entry (see Section 3.5). However, in some instances, testing facility representatives express
reluctance rather than actual refusal to allow an inspector to conduct an inspection. Often this reluctance
is due to a misunderstanding by testing facility representatives of EPA and/or testing facility
responsibilities under GLP regulations, or to concerns over perceived inconveniences to the testing facility
operations as a result of the inspection. Such concerns can often be resolved through diplomacy and
discussion but should not be subject to negotiation.
In such instances, an inspector should tactfully ascertain the reasons for testing facility officials'
reluctance and try to resolve the problems. The inspector should also explain in detail the purpose of the
inspection. However, it is crucial during any discussions that an inspector not agree to any restrictions
on the scope of a GLP inspection. In addition, the inspector must avoid issuing threats of any kind or
making inflammatory statements.
If entry is still denied, the inspector should withdraw from the testing facility and contact her/his
supervisor for further instructions. Under no circumstances should the inspector attempt to gain entry
or consent to enter by coercive actions or by making statements that suggest that the testing facility
officials could be fined or otherwise "punished" unless entry is allowed.
3.4.3 Conditional Consent
Conditional consent refers to any attempt by testing facility officials to restrict the inspection after entry
or to condition entry upon the adherence to restrictions imposed by the officials. The following are some
of the more common types of conditions that testing facility officials try to impose on the inspector:
• Waivers, indemnity agreements, or releases
• Photographic or tape recording restrictions
• Requirements concerning health and safety gear or training
• Denial of access to certain areas of the testing facility.
Generally, any attempt by testing facility officials to cause inspectors to deviate from standard inspection
procedures should be interpreted as an effort to impose conditions on .consent. OCM policy is that
inspectors should never agree to restrictions or conditions on the scope or nature of the inspection. The
inspector must never sign any document that could compromise EPA's right to conduct an inspection.
Any effort by testing facility officials to impose one or more conditions should be considered denial of
consent. In such circumstances, the inspector should follow the procedures governing denials of consent
(see Section 3.5). However, reasonable requests (such as requesting the inspector to wear a visitor's
3-7 September J99J
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CHAPTER THREE
badge, hard hat, or safety glasses) should not generally be considered "conditions," and the inspector
should comply with such requests. '
Even if the inspector is permitted to enter the testing facility without being asked to comply with
conditions or restrictions, the inspector should be constantly aware of any attempt by testing facility
representatives to impose such conditions after entry. If this should occur, the inspector must regard this
attempt as a denial of consent and follow appropriate procedures (continued in Section 3.5).
Some areas in which testing facility officials may attempt to impose restrictions are discussed below.
• Waivers and other restrictive agreements. EPA inspectors have the right and the
responsibility to refuse to sign any agreement or waiver that promises that records or
other data obtained from the testing facility will not be released to a third party or in
documentary form. Any attempt by testing facility personnel to restrict inspection
activities by requiring inspectors to sign such restrictive agreements should be viewed as
a denial of consent to inspect the testing facility and treated accordingly. (However,
inspectors should reiterate to the testing facility owner, operator, or agent in charge of
. her/his right to claim such data as CBI or a trade secret and of the procedures for making
such claims.)
• Restrictions on use of photographic or other recording equipment. Inspectors may
document evidence of potential violations at the testing facility by means of tape
recordings, photography, or recording by electronic devices with a visual taped readout,
or by other methods. Testing facility officials often attempt to restrict the use of any or
all of such devices by EPA inspectors. Any attempt by a testing facility representative
to restrict the use of such devices is considered a denial of consent and appropriate-
procedures governing such denials should be followed. Testing facility officials should
be advised that photographs and other information and data gathered by recording
equipment may be claimed as CBI (see Section 3.7.3).
• Health and safety restrictions. The inspector should ascertain the applicable safety
requirements before the inspection, if possible. The inspector should be aware that s/he
is subject to the applicable safety requirements of the testing facility. For example, if
safety boots and glasses are required to walk through a portion of the testing facility, then
the inspector must wear them. However, EPA inspectors cannot be required to
participate in the testing facility's safety training program (possibly very time consuming)
as a condition of conducting a GLP inspection. If testing facility officials make such a
demand, the inspector should refuse and treat the situation as a denial of consent.
• Refusal to allow access to certain areas of the testing facility. If, during the course of the
inspection, access is denied or restricted to certain areas of the testing facility, the
inspector should make a notation describing such denial or restriction in the field
notebook and identify which portion of the inspection could not be completed due to the
denied or restricted access. However, despite the access restriction, the inspector should
proceed with the remainder of the inspection. After leaving the testing facility, the
inspector should contact her/his supervisor to determine the appropriate action(s) to take.
CLP Inspection Manual 3-8
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IfGPECTIOH PXOCEDUKSS
3.4.4 Withdrawal of Consent
Occasionally, testing facility officials may initially consent to an inspection but later withdraw the consent
during the inspection. Consent to the inspection may be withdrawn at any time after entry has been
made. OCM policy concerning withdrawal of consent is to view it as an outright denial of consent. In
such cases, appropriate procedures should be followed (see Section 3.5). All activities and evidence
obtained prior to the withdrawal of consent are valid. Therefore, evidence obtained by the inspector
before consent was withdrawn is usable in any subsequent enforcement actions and should be retained
by the inspector. The inspector should not return any evidence that has been collected before the
withdrawal of consent if asked to do so by the testing facility official.
3.4.5 Inspector Judgment
Whenever it appears that testing facility officials,-through statements or actions (such as physically
blocking entry), are denying or restricting consent to conduct the inspection authorized by FIFRA or
TSCA, the inspector must use independent judgment to determine the actual effect the limitation will have
on the inspection.
Sometimes inspectors are able to reach an agreement with testing facility representatives. Inspectors
should keep in mind that attempts to negotiate with testing facility officials are based on the independent
judgment of the inspectors and, as such, involve risks (e.g., having a court declare later that consent was
obtained coercively and, therefore, was not consent). If the inspector is in doubt, s/he should consult the
appropriate supervisor, or counsel before proceeding.
The inspector always has the option of departing the testing facility premises and advising his/her
supervisor. The inspector can choose to discontinue the. inspection at any time after the inspection has
begun. The following examples illustrate how inspectors could handle situations that might be considered
denials of entry:
• Restrictive language in sign-in book or form. The inspector should draw a line through
objectionable language before signing, obtain a photocopy, and make a note in her/his
field notebook. The inspector must inform the testing facility officials of the modification
s/he made and request that a testing facility official initial the modification.
• Photographs. When testing facility officials state they do not want photographs taken of
the testing facility, the inspector can proceed with the inspection, raising the issue of
photographs again only when a particular photograph is essential to the inspection. If
photography is still not permitted, the inspector can follow the procedures for securing
and executing a warrant (provided in Section 3.5).
• Safety training. While inspectors are not required to participate in a testing facility's
safety training course prior to entry, if the testing facility has a relatively short safety
briefing that will not interfere with the inspector's ability to complete the planned
inspection in a timely manner, the inspector may want to attend the briefing. Inspectors
3-9 September 1993
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THREE
are sometimes able to learn valuable information about the testing facility's layout and
operations at such orientations. If safety or facility liability concerns are raised by the
facility representative, the inspector should inform the representative that EPA inspectors
are required to undergo health and safety training prior to receiving inspector credentials.
The inspector should be sensitive to efforts that may be made during the course of the inspection to limit
or interfere wirn his/her activities. These may range from the subtle, inefficient wasting of the inspector's
time to imposing restrictions (discussed previously). If the conduct of the inspection is being
compromised, the inspector should regard the situation as withdrawal of consent and proceed as described
in Section 3.5.
3.5 DENIAL OF CONSENT To ENTER AND INSPECT
The first thing that an inspector must keep in mind when testing facility officials deny consent to conduct
a GLP inspection or any portion thereof is to refrain from making any inflammatory remarks or
statements that could jeopardize subsequent enforcement actions brought against the testing facility. For
example, the inspector must not discuss any potential penalties that are authorized under Section 14 of
FIFRA or Section 15 of TSCA for refusal to permit entry or inspection. If such potential penalties were
discussed and consequently testing facility officials permitted the inspection to be conducted, officials
could later claim such statements were a form of coercion. A court could rule at a subsequent proceeding
that some or all of the evidence collected during the inspection is inadmissible. As another example, the
inspector should not threaten testing facility officials with the fact that s/he will "get a warrant," even
though OCM may later try to secure a warrant to conduct the inspection. This is because a court of law,
which later may review the search procedures used by OCM, may interpret the statement as coercive,
invalidating the search.
In the event that entry is denied, the inspector should write the following information (which will be
helpful should OCM decide to obtain a warrant at a later date) in her/his field notebook:
• Testing facility name and address
• Name, .title, and telephone number of person who refused entry
• Name, address, and telephone number of the testing facility's attorney (if available)
• , Date and time of refusal
• Reason (if given) for testing facility's refusal to allow the inspector to enter and/or to
inspect testing facility
• Description of testing facility appearance, including number of buildings and general
observations, such as housekeeping practices
CLP Inspection Manual 3-10
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PXOCZDUHES
Any reasonable suspicion that refusal stemmed from desire to prevent discovery of
regulatory or statutory violations.
After making the above notations in her/his field notebook, the inspector should immediately leave the
premises and contact her/his supervisor, who will confer with the appropriate counsel concerning the
desirability of obtaining a warrant. The inspector should assure that the testing facility officials have been
given (or offered) a copy of the written Notice of Inspection to show mat proper procedures were
followed.
Generally, after counsel is contacted, s/he will discuss the matter of the inspection by telephone with
testing facility officials in order to resolve the issues surrounding the inspection. If the matter can be
resolved in this manner, the inspection should proceed without further delay. However, if counsel is
unable to solve the problem, the inspector should discuss with her/his supervisor the possibility of
obtaining a warrant. If the decision is made to obtain a warrant, the EPA attorney will contact the U.S.
Attorney's office for the district where the facility is located. The EPA Attorney generally will arrange
for an Assistant U.S. Attorney to meet with the inspector as soon as possible.
3.6 THE OPENING CONFERENCE
3.6.1 Purpose
Once the inspector has presented her/his credentials and the required notice for conducting an inspection,
it is time for the opening conference. The inspector should ask whether a conference room or office is
available where s/he can conduct the opening conference and review testing facility records and files.
The opening conference provides an ideal opportunity for the inspector to strengthen EPA-industry
relations. The inspector's role, in addition to that of assessing compliance at testing facilities subject to
GLP standards, should be that of public relations liaison with the regulated community. The inspector
can serve in this role throughout the inspection, but especially during the opening and closing
conferences.
The inspector should be prepared to demonstrate her/his thorough understanding of the major sections
of FIFRA and TSCA (i.e., those under which the compliance reviews are conducted) and applicable
regulations. Industry representatives will also be familiar with the requirements of the regulations in
order to comply with the law. Therefore, it is crucial for inspectors to be well-versed in the regulations
promulgated pursuant to FIFRA and TSCA, including any new regulations, as they are published in the
Federal Register. The inspector should always have copies of relevant regulations on hand. During the
course of an inspection, it also may be necessary to refer some facility questions or requests (e.g., for
TSCA-related publications) to the TSCA Hotline (202-544-1404) or to refer other matters to appropriaie
EPA Region or Headquarters staff.
During the opening conference, the inspector should have the following objectives:
3-11 September /W»
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THREE
Confirm thai his/her credentials have been presented and accepted.
Confirm that consent to enter has been given by the facility official.
Present either the FIFRA Notice of Inspection or the TSCA Notice of Inspection and the
TSCA Inspection Confidentiality Notice as required.
Inform the facility representatives of the nature of the inspection (i.e., routine or for
cause). If it is a for cause or priority inspection, evidence gathered may be jeopardized
if the facility has not been informed.
Introduce and properly identify the members of the inspection team.
Schedule the inspection activities (including the closing conference).
Request appropriate documents such as master schedule, training records, SOPs, testing
facility general information, floor plans, and organizational charts.
Request records, such as protocols and raw data, that are required for study audits.
Select a recently completed study to be used as an aid for the compliance review.
Request a testing facility walk-through for the entire team.
Update existing information on file for the testing facility at EPA Regions and
Headquarters.
Establish a rapport with testing facility officials.
Conduct the meeting in a positive and professional manner.
Answer questions concerning FIFRA, TSCA, and applicable regulations.
Do not overstep authority to accommodate testing facility officials (e.g., do not give
opinions about the acceptability of testing facility practices or whether the testing facility
is in compliance with the applicable regulations).
Establish ground rules, working hours, etc.
Obtain history, scope of operations, recent management changes, business affiliations.
etc.
3.6.2 Ptocedi
The inspector should begin the opening conference by outlining inspection objectives in general terms to
inform testing facility officials of the purpose and scope of the inspection. The inspector should, it
necessary, present the testing facility owner (or her/his designated agent) with the TSCA Inspection
Confidentiality Notice (Figure 3-3). It should be noted that no equivalent FIFRA form exists. This
CLP Inspection Manual 3-12
-------
INSPECTION
FIGURE 3-3.
TSCA INSPECTION CONFIDENTlALnT NOTICE
^Bk •a^eHC*, «m ''• WASHINGTON. DC }04«0 -,'~ tooro.n,
mm I I mm% out +, toroooo'
^•^ f™ -MX* r°X'C SU8STAMCtS COWTHOL ACT (,„,., j 3, it
^J •"•• «^» TSCA INSPECTION CONFIDENTIALITY NOTICE
1. INVESTIGATION IDENTIFICATION
DATE 1 INSPECTOR NO. OAII.Y SEC. NO.
3. INSPECTOR NAME
5. INSPECTOR AOORESS
TO AJHHT A CONFIOINTIAL.
It it ooaibie trot EPA will receive ouMic reauero for reieeee of tne
information ootamed aurimj meaecnon of me facility move. Sucn
reouem will b* Handled bv EPA in accordance witn prevision a* me
Freedom of Information Act IFOIA). 9 USC 582: EPA regulation
iaued thereunder, 40 CFR 'irt 2: »nd tn« Toxic Suoaancet Control
Act (TSCA). Section 14. EPA it rwjuired to make ineoection cwu
available >n rmoen* re FOIA reoua*ti umeei in* Adminimtor of me
Agency oeterminei met tn« an* contain information entitled to confi.
d*nti« tn«tm*nt or m«y M oiitirwld from rti«n» anotr omir tion-
tiora of POlA.
Any or Ml trw information eolKend bv EPA durinf tfw inw*ction m«v
»• cKimad confidtntiM if it norm to mat mcrm or oomnMreM or
finanox man«n mat you conudar to M confldann*! buainaai infor-
mnion. If you aaiart t C8I oaim. EPA Mil dltaota tna informaoon
only to tn« ixttm. ind Dv m**ni of If* oroeMuraa an (arm in tna
regulation (otad aaowil oo«annnt EPA'i uaauiiaiil of oonfioantial
buunaat information. Arnonf 9tff«r tninoa. tna raguiationi raQuira mat
EPA notify you m tavuntf of Btfliicly ditooain*, my information
you nav* daimao u confidannal buwnaai informainx.
A confidential ouuflaai information IC8I) daim may oa aaMnad at any
lima. You may aaMrt < C8I claim oner to. Ourirn. or afear ma infor-
mation i* ceilaend. Tha daeamon form ma mmucaa bv tna Aoaney
•aMrt • C8I daim on your own itationary or By martin^ tna indi>ndua<
oocumanti or ajmaai "TSCA eonfidannal buainaa information," It n
not nacaaary for you to u*f ttin form. Tha II^KLUJI will Oa fta To
iniwar any quaationt you may navt rioarOinf ma Aotncy'i Cll
procaourii.
Whila you may aaim any ooiwrtad information or lamott • confl«n.
tut Ouunaej information, ajoi aainw art unlikafy to ba uonaM if may
«ra cnatianoad uniaai tna information iriaau ma fotMMinf critana:
1 . V our eomoany naa okan maaauni to orotaet ma oonrl.
aantiMitv of ma information, and it intanda to continue
to take lucn maaauna.
TO BE COMPLETED BY FACIUTY OFFICIAL RECEIVING THIS NOTICE:
1 nfM raoanMO anaj rvao tnv noviov
•SIGNATUMI
.NAMf
TITLC OATI SIGNf O
2. FIRM NAME
4. FIRM AQORE55
6 C E : c E E 0 C
7. TITLE
8U3INUS INPOKMATIOM CLAIM
2. Tha information n not, *nd ha§ not been, renonaoiy ootamaDia
wttnout your comoany'i conajnt by etner oanoni lotnar inin
90 «*m mental bodiaal by uee of 'eoitimatt maani lotnar tnan
aiacooery baaao on inowing of ajeaal need >n a mdicial or
auaaiiudiaal orocaaaino).
3. Tha information it not ouMicty Milabte aiaiwnent.
4. Oiaeioaurt of me information would cauaa •jbruntiat
narm to your comoaro'i oomaatitrM ooanion.
At ma eompiatton of ma inaaaerion. you will ba on«n t raeaiot for itl
oocumemt. a»nom. and otnar mavriaii eoilacad. At tn«t tima. you
may maka claim* met «ama or Ml of ma information n canfidantiai
bunnavi information.
If you are not autnonxad bv your company a eewrt i C8I claim, thn
notice will oa ant by certified mail, atone, oitn tna reeaiot for docu-
mantt, •moiai. and otnar manriaM to tna Chief Executive Officer of
your firm wrttiin 2 d*v< of mit data. Tna Chief Execunva Offlotr mun
rtnim i «ji»ii«iii ajecrfvina any information wnicn would recaive
confidantia) uaauiieiu.
The ftatament from ma Chief Executive Officer tnouid ba aadreoed
to:
•TK) mailed bv iea,»tarad. r*tum-r«ea>ot reouerad mail witfiin 7 calan.
dar davi of mcaiot of tn» Notice, damn may ba made any time
ifter tna meBection, but mtoanion dan will net ba entered into me
iceci* •cunry ryrtam for TSCA confidential bueineai information
until *n official confidentiality claim * made. The data will ba handled
under me apaney'i routine aKuntv lynam unira and until a claim «
maoa.
If then it no one on tne oremiaM of me facility wno n eutnontea to mail
bunneei confidantialiry ciaima for tna firm. » too* of mit Notice and otnar
moMction matariaii will ba »m to me comeanyi cnwf iiecutive officer, if
cxeeea oexarwn Dexjw.
NAMI
TITLI
Abfi^cu
EPA farm TltO^ 112-13)
INSKCDON flL£
3-13
September 1993
-------
CHAPTER THREE
notice informs the testing facility representative of the right to claim any information (e.g., documents,
records, physical samples, or other material) collected from the testing facility during the inspection as
CBI. In a TSCA GLP inspection, testing facility officials should also be briefed on EPA's TSCA CBI
procedures (see Section 2.8.1).
The inspector should then describe the inspection plan (see Section 2.3) to testing facility officials. By
describing the inspection plan, the inspector fosters an atmosphere of cooperation between EPA and the
testing facility, which is important for ensuring an understanding by both parties of GLP compliance
issues. By keeping the discussion of the inspection plan general, the inspector can avoid providing
advance warnings to testing facility officials.
During the opening conference, the inspector should review with the facility management the anticipated
schedule of the inspection, particularly if this is a first-time inspection. A typical inspection agenda
includes:
' • Opening conference
• Facility walk-through
• Review of general facility literature and information
• Review of records, including SOPs and training records
• Compliance review using an on-going study as model
• Evaluation of archives
• Evaluation of the Quality Assurance Unit
• Facilities, equipment and records evaluation
• Evaluation of test, control, and reference substance handling and records
• Closing conference, including issuing receipt for samples.
The'facility personnel should also be made aware of what the auditor's activities and needs will be while
the inspector is conducting the compliance review.
The most important objective of the opening conference is to obtain as much information concerning the
particular testing facility's operations and practices as possible. In addition, die inspector should use the
opening conference to question testing facility officials about such practices, operations, and any other
data that may not have been included in EPA records or that require clarification. The inspector should
refer to the testing facility's organizational chart to learn who is in charge of what operations at the
testing facility and who to contact for additional information.
To save time, the inspector should resolve logistical issues at the opening conference in preparation for
the actual inspection. The following factors should be considered:
CLP Inspection Manual 3-14
-------
Having a testing facility official accompany inspector. Before the inspection is
conducted, make arrangements for a testing facility representative to accompany the
inspector on the inspection. The representative should be able to describe testing facility
layout and operations and to indicate what data, records, etc., should be claimed as CBI.
(Testing facility claims of confidentiality may be made only by an individual with the
authority to make such claims, as discussed in Section 3.7.3.)
Testing facility walk-through. At the conclusion of the opening conference, the
inspection team will typically tour or walk through the testing facility. This can serve as
part of the inspection or compliance review and it can also serve to familiarize the other
team members with the testing facility to make the audits more efficient. Since the
inspector will normally have additional time to inspect the testing facility in greater detail,
care should be taken to make sure that the testing facility staff does not use an inordinate
amount of the team's time on this walk-through.
Schedule of inspection. Arrange for a schedule of necessary meetings to be developed,
based on the inspection plan and the inspector's understanding of the responsibilities of
various testing facility officials. This schedule will allow individuals.enough time to
prepare for discussions with the inspectors. Set a specific time and place for the closing
conference (see Section 3.7). This conference will provide a final opportunity to gather
information from testing facility officials, to answer questions, and to complete
administrative duties. The closing conference will also provide a forum for summarizing
the inspection.
Master schedule: selection of an ongoing or recently completed study. The inspector
should select an ongoing study from the master schedule to use as a means of carrying
out the GLP compliance review. The inspector should select an ongoing study covered
by the regulations in which the inspection is being carried out. For example, if it is a
FTFRA inspection, a study that will be submitted under FIFRA should be selected.
Facility document^. As part of the opening conference, the inspector should indicate
those facility documents s/he will need to review during the course of the inspection, so
that the facility personnel can have time to gather the materials. These typically include
SOPs, staff training records including resumes and curriculum vitae, quality assurance
records, etc. The inspector should also request (particularly if this is a first-time
inspection of a new facility or if there have been significant changes to the facility since
the last inspection) copies of floor plans, organizational charts, brochures, etc., for use
in preparation of a complete report.
3.7 THE CLOSNQ CONFERENCE
3.7.1 Purpose
The purpose of the closing conference is to allow the inspector and testing facility representatives to
resolve final administrative matters concerning the inspection. Ideally, the closing conference should be
scheduled for the morning after the conclusion of the GLP inspection. The closing conference should
accomplish the following:
3-15 September 199J
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TBRES
Summarize the inspection proceedings.
Review all significant inspection findings for facility personnel, clarify any issues, and
answer any questions related to the findings.
Complete and submit to testing facility representatives certain forms related to the
inspection (see Section 3.7.3).
Obtain from testing facility officials any outstanding records or other data needed by the
inspector.
Issue a TSCA Receipt for Samples and Documents and/or a FIFRA Receipt for Samples
and allow facility officials to make any confidentiality claims for documents collected
during the inspection.
Make specific arrangements for any .additional documents or information to be provided
to the inspector.
The inspector should be certain that all appropriate facility personnel will be present. At the very least,
this should include management and the study directors. Often, however, the facility will also wish to
have others attend, such as technical personnel, attorneys, and corporate or sponsor representatives. It
is up to the inspector what, if .any, limits should be placed on attendance at the closing conference.
i
3.7.2 Pre-Closing Conference with Inspection Team
Prior to the closing conference, the inspector should meet with inspection team members to review and
discuss inspection findings. It is imperative that the inspector be aware of any problems found by the
auditors, and s/he may need to provide guidance to the auditors, especially in determining the significance
of negative GLP findings relating to the audited studies. The auditors must also make sure that the
inspector understands the significance of any technical or data deficiencies in the studies. No "surprises"
should arise during the actual closing conference.
The inspector should determine from each auditor if there.are any unresolved issues, if any followup
information or records must be requested from the testing facility, and if each auditor has obtained copies
of all necessary records or data that were requested and are needed to document any negative findings.
The inspector should also establish the order in which findings will be presented.. Normally, each auditor
will present his/her own findings. However, there may be occasions when an auditor is unwilling to
speak (e.g., s/he may not be fluent in English) and may prefer to have someone else present the audit
findings. The inspector should make these arrangements beforehand.
GLP Inspection Manual 3-16
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IfGFKCIION
3.7.3 Procedures
The inspector serves as the moderator for the closing conference. The same objectives that govern the
manner in which an inspector should conduct the opening conference (see Section 3.6) apply to the
closing conference as well. The inspector should make a record of the facility personnel attending the
closing conference, particularly if problems were encountered during the inspection or there are
significant negative findings. The inspector and appropriate team members should summarize the
inspection findings in an objective and factual manner. During the conference, it is critical that the team
refrain from drawing conclusions regarding any potential violations that may have been discovered during
the inspection. Enforcement policy and issues should not be discussed. Any questions related to these
areas should be referred to Chief, SSB.
The inspector should clarify any final questions and provide the testing facility officials with the
opportunity to ask any final questions. If the inspector wants to obtain additional documents not available
at the time of the closing conference, the inspector should request these documents and agree upon a
reasonable date by which the testing facility officials should submit the documents. However, the
inspector should make every effort to obtain all necessary records during the inspection, thus keeping the
need for followup information to a minimum. The inspector should request that any documents that the
company may decide to submit to EPA Headquarters or correspondence with EPA resulting from the
inspection be copied and sent to her/him.
Areas of disagreement between the inspection team and facility personnel may arise during the closing
conference. If these cannot be resolved to the satisfaction of all parties, the facility may be given the
opportunity to respond to specific inspection findings in writing. The facility is under no obligation to
provide written responses and the inspector is not under any obligation to include such a response in the
final report. However, misunderstandings often may be resolved in this manner, and a written
explanation of an inspection finding may be useful to include in the final report.
A separate issue is that of recording the closing conference. Commonly, the facility representative will
request that the proceedings be tape-recorded; less frequently, s/he may request videotaping or verbatim
stenography (as by a court reporter). As a general policy, the closing conference should not be recorded.
However, the inspector has the discretion to make an exception to this policy under special circumstances.
If such is the case, the inspector must stipulate that a copy of the recording or transcript be provided to
him/her as part of the inspection documentation.
During the closing conference, the inspector must also require the testing facility officials to complete
two forms related to the inspection process. These forms are the TSCA Declaration of Confidential
Business Information (Figure 3-4), if necessary, and the FIFRA Receipt for Samples and/or the TSCA
Receipt for Samples and Documents (Figures 3-5 and 3-6).
3-17 September 199}
-------
CH.\J*TEX THREE
FIGURE 3-4.
TSCA DECLARATION OF CONFIDENTIAL BUSINESS DEFORMATION
jf^ •••^ JK WASHINGTON, gc 2o**o
^l*g ki K^vX TOXIC SUBSTANCM CONTROL ACT
^^ f * DECLARATION OF CONFIDENTIAL BUSINESS INFORMATION
1. INVESTIGATION IDENTIFICATION 2- FIRM NAME
DATE
inaj-tCTofl NO. DAILY SEQ. NO.
tymannmr
a** *• ;o?o-at»7
f/»r» J J( M
3. .NS?6cVifl A2CRESS 4. FIRM ADDRESS
INFORMATION OCSIONATSO AS CON» IOENTI A L. SUSINCS* INFORMATION
NO. OCSCniFTION
ACXMOWLEOGEMENT BY CLAIMANT
Tht undtnifrad «tknB»
-------
INSPECTION PROCECHJHES
FIGURE
FIFRA RECEIPT FOR SAMPLES
*>«•"">.
U.S. ENVipOHnEHTAi. •>9QTECT:ON ACeNCT
RECEIPT FOR SAMPLES
SAMPLE N
The following samples were collected by the U.S. Environmental Protection Agency and receipt is nerebv acknow-
ledged persuant to Section 9.(a) of the Federal Insecticide, Fungicide, and Rodenticide Act, as amended (7 U.S.C.
136 g ). This section is quoted on the reverse ot' this form.
ACXNOVUEOCMCNT OF PRODUCER REGISTRANT
The undersigned acknowledges :hat the samples shown above -*ere obtained rroir pesticides it devices that
packaged. labeled, and released for shipment
SICNATUBI rOmmm. O*»raror. or
- 3u»'-:C*TE
p«pviocs —
AMOUNT OHO 'OK SAMPi.gJ
NAME 3' COL.-.EC"* -C>r
EPA ^>n« ]540-1 (K«». 1-75)
ESTA8USHMENT COPY
3-19
September 199]
-------
THREE
FIGURE 3-6.
TSCA RECEIPT FOR SAMPLES AND DOCUMENTS
US KNVIflONWI.STAu • •QTfCTlON *GtNCY
^P>m ^^"^^^^ J& ' Fann Acorovta.
^^•p. &_ ^Jfl TOXIC SUBSTANCES CONTMOL ACT CMS No. 2070-0007
^^^f f^ k^^P*1* Aoorovu cum J-31-sa
^•^ fc-l *» RECEIPT FOR SAMPLES AND DOCUMENTS
1. INVESTIGATION IDENTIFICATION 2. FIRM NAME
DATE
iNS^tCTGK no. DAILY SEQ. NO.
3. INSPECTOR AflflAEii 4. FIRM AUDHtiS
The document! and umplet at chemical subnancei and/or mixtures described below were collected in connection witti trie
administration and enforcement of me Toxic Substances Control Act.
RECEIPT Of THE DOCUMENTS) ANO/OM SAMPLEISI DESCRIBED IS MEREIY ACXNOWLEDQED:
NO.
OCSCniPTlON
OrriOMAL:
OU'LICATt OM VLIT SAMPLES: "IQUI3T1O AND '«OVIO€D CZ NOT M(Ouf STtO LJ
NS^eCTOK SICNATUMI •EClPliNT SICNATUHI
NAMt NAMf
EPA Form 7740-1 (12-82)
1 ' iNSPeCTOfl'S FILE
CLP Inspection Manual
3-20
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INSPECTION PXOCEDUKES
The copy of the FIFRA Receipt for Samples or the TSCA Receipt for Samples and Documents.
whichever is applicable, lists and describes each document and sample taken by the inspector from the
testing facility. This receipt must be signed and dated by a testing facility official and the inspector. The
receipt should identify the following:
• A description of all physical samples taken (if any)
• A description of all records, photographs, or other property taken (particularly crucial
when inspecting with a warrant)
• A brief description of information claimed as TSCA CBI (which should be listed on the
TSCA Declaration of Confidential Business Information form).
The purpose of this detailed receipt is to document that testing facility officials knew exactly what
documents and samples were taken and to allow for full review by testing facility officials so that
confidentiality claims can be made.
Many times the facility will routinely consider all documents, both FIFRA and TSCA, to be confidential
and will stamp them in some way to indicate this. The inspector should not suggest or advise that any
document or other item be claimed as confidential. The decision must be left entirely to the testing
facility official. CBI claims should be considered for review and challenge in a manner consistent with
the requirements of 40 CFR §2.203 and are the responsibility of the Office of General Counsel. IMD
personnel can provide assistance to the inspector in reviewing TSCA CBI claims to determine if they are
valid.
The TSCA Declaration of Confidential Business Information form must include a list of all documents,
photographs, or other data claimed by an authorized testing facility representative as TSCA CBI. The
inspector should keep in mind that some data may have been declared CBI during the inspection. These
items should be confirmed with testing facility officials and included on the CBI declaration form. Both
the inspector and the claimant (i.e., the testing facility official) must sign and date the completed
document.
All documents for which a CBI claim has been made must subsequently be handled according to the
custody requirements of the CBI regulations. Therefore, CBI documents should be collected only when
necessary to document a potential violation, and the inspector must have determined beforehand that s/he
or the auditor has.the necessary facilities and procedures in place to meet the CBI requirements.
If there is no onsite testing facility official authorized to make CBI claims at the time of the closing
conference, the inspector should:
• Make a copy of the completed and signed FIFRA Receipt for Samples or TSCA Receipt
for Samples and Documents.
3-21 September 199}
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COASTER THREE
• Make a copy of the completed and signed TSCA Inspection Confidentiality Notice.
• Complete the top portion only (i.e., investigation identification information, firm name,
. inspector address, firm address) of the Declaration of Confidential Business Information
form.
• Mail the forms certified, return receipt requested to the Chief Executive Officer (CEO)
of the testing facility within 2 days of the inspection. (The CEO will have 7 calendar
days to make CBI claims on the declaration form.)
The inspector need not take any measures during the 7-day period mentioned in the last item above
beyond following the routine security procedures normal for inspection data collected from the testing
facility. However, immediately upon notification of the DCO by the appropriate testing facility officials
(i.e., those authorized to claim CBI) that data are being claimed as CBI, EPA will commence TSCA CBI
procedures with respect to such data. If a CBI claim is made, it is the responsibility of the DCO to notify
all parties (i.e., inspector, testing facility, case preparation staff, and any others who may be handling
the information) of the fact that the material is CBI and to log the material as required.
3.8 EVIDENCE COLLECTION AND ACCOUNTABILITY
The inspector or auditor will document in the inspection report for potential use as evidence all GLP
deviations and deficiencies, and all data discrepancies and gaps. The evidence will be used to support
any enforcement or regulatory action EPA takes. This evidence may consist of the following:
• Field notebook entries
• Photocopies of raw data, records, reports, or correspondence
• Personal statements
• Photographs
• Sample or specimen analysis or evaluation.
There should be no assertion or description of a GLP or data problem in an inspection report without
proper supporting evidence. Occasionally, documents may also be collected strictly for specimen
purposes or to verify correction of a previously identified deficiency. Copies of data, records, etc., may
also be collected to allow further detailed review by the inspector, auditor, or other designated expert at
a later date. These documents may or may not eventually be used as evidence. In all cases, collection
and subsequent handling of these materials must be done using the procedures described here. Inspectors
should review the relevant chapters of the Pesticides Inspection Manual and the Basic Inspectors Manual
for further guidance on evidence collection and accountability.
GLP Inspection Manual 3-22
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Ifcffcijon PKOCEDUKZS
3.8.1 Field Notebook
The field notebook or the inspector's/auditor's personal notes will constitute the principal means of
organization for evidence collection for each GLP inspection and related study audit. The field notebook
will also serve as a source for describing the overall inspection, personal statements, records collected
or requested, calculations, and other information. Observations of operations, facilities, equipment,
personnel, and other topics will also be recorded in the notebook.
Each inspection team member will have his/her own notebook. A separate notebook should be used to
record information for a single facility. Notes from multiple study audits may be recorded in a single
notebook as long as all audit findings are distinctly identified and reflect audits conducted at a single test
facility.
The first page of the notebook should be identified with the inspector's (or auditor's) name, the facility,
the date(s), and if available, the EPA inspection number. Any business cards collected during the
inspection may be stapled along the edge of the opening or closing page. They should not be
paper-clipped or left loose in the notebook.
Since the field notebook represents the single most important reference for the inspection report and for
any subsequent legal support that may arise out of an enforcement action, care is to be taken with derail,
legibility, thoroughness, and accuracy. All entries are to be adequately identified and dated, and each
person interviewed identified by name, title, and association with the work under review. The field
notebook is to contain only facts and observations. Under no circumstances should a field notebook
contain any personal opinions or prejudgment as to whether or not a violation has occurred.
The field notebook is considered EPA property and, as such, is to be retained in the appropriate
evidentiary files along with the final inspection report and other related documents.
3.8.2 Copies of Data, Records, Reports, and Correspondence
Photocopies of raw data, records, reports, and correspondence will serve as the primary source of
evidence when documenting GLP/study audit problems. All documents necessary to prove a violation
should have been collected by the inspector. For example, in a FIFRA GLP compliance inspection, the
inspector should be sure to obtain the compliance statement of each study. In addition, if an inspection
is focusing on an ongoing study, the inspector must collect evidence that the facility knew the study was
going to be submitted to EPA.
Most larger laboratories and testing sites have photocopying facilities and will reproduce a reasonable
number of copies at no cost. For other facilities, such as smaller laboratories or remote field sites, the
inspector should ascertain, prior to the inspection, whether photocopying capability will be available
onsite. If not, arrangements must be made to:
3-23 September 19')
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CHAPTER THREE
• Have the documents reproduced at a commercial copying facility during the inspection
and recover the cost via travel voucher or petty cash, or
• Arrange to transfer the necessary original documents to the EPA office for reproduction.
In either case, an appropriate .FIFRA or TSCA receipt (see Chapter 2.8) should be issued if the
documents are removed from the inspected facility, unaccompanied by a facility representative. If
documents are copied at the EPA office, the originals should be immediately returned to the facility by
hand delivery or by certified mail. In either case, a written acknowledgement of their receipt by an
official from the facility should be obtained.
When photocopies of documents are received or made by the inspector, each page must be examined and
compared to the original to assure it is an acceptable copy and that the GLP deviation or data discrepancy
is clearly evident. If colored inks were present in the original and were not reproduced on the photocopy,
the inspector should indicate the colored portion on the copy via arrows or encirclement, and should
initial and date the notation(s) in contrasting ink. If the potential violation involves an entry in pencil,
a white-out, or other circumstance that is not evident on the photocopy of the document, then the
inspector should indicate the deviation with an arrow and/or encirclement and explain it briefly on the
document. If possible, these notations should be initialed and dated by both the inspector and a witness.
The witness should preferably be another EPA employee or representative; however, it may be a facility
official or third party if circumstances warrant. The inspector's and witness's notations should be made
with a contrasting colored ink. An arrow stamp can also be used in similar fashion to highlight a
particular data or procedural discrepancy on a photocopied document. In addition, each document (or
document set) should be listed on the FIFRA Receipt for Samples or TSCA Receipt for Samples and
Documents at the close of the inspection (see Chapter 3.7.3).
Related documents should be combined, as appropriate, to form a document set. The various sheets,
consisting of copies of raw data for a particular study, may be one document set; a copy of the protocol
would be considered a separate document set. The location of the original documents in the facility's
archived files should be fully described in the field notebook so that these materials may be readily
located at a later date, if necessary.
The reverse side of the first page of each collected document set is to be stamped or identified as follows,
with the appropriate information filled in:
Inspection:
Doc. No: '
No. Pages: ,
Date: By:.
GLP Inspection Manual 3-24
-------
IftSFfCIJON PXOCEDUKSS
The Doc. No. should correspond to the listing on the TSCA or FIFRA receipt. Every page of each
document set Is then identified on the front in the lower righthand corner with the inspector's initials and
the date of collection.
The inspector will collect and maintain all collected and identified documents as a master set of exhibits
for each official inspection or investigation. Additional copies may then be distributed to the auditors,
either before leaving the site (if multiple copies can be conveniently obtained) or after photocopying upon
the inspector's return to the office. In the latter case, the necessary additional copies should be
transmitted to the auditors) as expeditiously and securely as possible.
Followup information or documents received by the inspector after the onsite phase of the inspection is
completed will be bandied in the same manner (see Section 6.2).
When a document set (or a portion thereof) is ready for insertion as an exhibit into the final inspection
report, each page shall be additionally marked with the exhibit number and the exhibit page number.
3.8.3 Signed Stat
In some circumstances, a signed personal statement from a facility representative may be necessary to
fully document an inspection problem, such as in the case of unretained raw data or when potential GLP
violations or data problem(s) cannot be fully documented by other means. To the extent possible, signed
statements that document any potential violation should be collected.
The statement, which may also be in the form of a letter, should be prepared and signed by a responsible
management official or study director who represents the facility or company. Statements may also be
obtained from technical and QAU staff, as appropriate. All personal statements should be acknowledged
via official FIFRA or TSCA receipt or by letter.
Of particular concern to the EPA inspector or auditor is the case of unretained or missing raw data. Not
only does this situation constitute a potential violation of the GLP regulations (40 CFR §160.195 and
§762.195), but in the case of data related to registered pesticides, it is also a potential violation of the
FIFRA books and records regulations [40 CFR §169.2(k)]. Thus, both sections should be cited in the
inspection report when registered pesticide products are involved.
A signed statement from a test facility representative should also be obtained, if possible, when a potential
violation is discovered as a result of an interview. The substance of the allegation may be documented
in a statement, prepared and signed by the individual, that clearly describes the situation in question. In
addition, substantiating evidence in the way of document copies or photographs should also be collected.
3-25 September 1993
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CHAPTER THREE
3.8.4 Photographs and Observations
In some situations, a photograph or series of photographs is the most effective or only way to document
a GLP deviation. Photographs may also be used to enhance the effectiveness or validity of other
documentation. Problems associated with facilities, test substance description, equipment, or
specimen/reagent labeling, are examples of areas that may lend themselves to photographic
documentation.
Some facilities or corporations have policies prohibiting photography or possession of cameras on
company property. If photographs are necessary, arrangements can usually be made with facility
management to provide a duplicate set of photos or to have facility personnel take side-by-side
photographs. Assurance of confidentiality regarding the necessary photographs may also expedite
permission. If permission is still refused, this is considered denial of consent (see §3.4.3), and
supervisory and/or legal assistance should be obtained by the inspector, particularly if alternative evidence
is not available.
Either an instant print (e.g., Polaroid) or 35-millimeter camera may be used; however the latter will
provide better quality prints for use as evidence and can be enlarged, if necessary. An instant print
camera has the advantage, however, of providing an immediate image to assure that the necessary
information was captured. In critical situations, both cameras should be used, with the instant film prints
serving as backup if the 35-millimeter prints prove to be unsatisfactory. If a declaration of TSCA CBI
is made (or is anticipated), photographs should be taken with an instant print camera, particularly if a
developing facility cleared for TSCA CBI is not readily accessible.
All photographs taken as part of an inspection should be fully described in the field notebook with date
and time, subject matter, distance, direction, witnesses, exposure data, film type, and other supporting
information. Some cameras will automatically provide date and time, as well as sequence number on the
negative. When prints are received, whether instant film or 35-millimeter, each should be identified in
ink on the back or in the margin with print number, date, inspector's initials, facility, and brief
description of subject matter. Computerized label-making systems may also be used.
All photographs should be described on the FTFRA or TSCA receipt, including a notation if duplicate
prints are to be (or have been) provided to the facility.
The following references provide the inspector with some introductory technical guidance when taking
photographs for use as evidence.
"Fundamentals of Photography for Government," 1986, U.S. EPA Region 10, Seattle.
WA
CLP Inspection Manual ' 3-26
-------
ItSPfCIION PXOCKDUKS
• "Basic Inspector Training Course: Fundamentals of Environmental Compliance
Inspections," Chapter 15B, 1989, U.S. EPA, Office of Enforcement, Washington, DC
• "Federal Law Enforcement Training Center: Student Text, Photography ST-39.1/.2,"
1977, U.S. Department of the Treasury, Washington, DC.
3.8.5 Physical Sampling (Nondocamentary Samples)
Although the inspector will rarely need to collect nondocumentary samples (i.e., physical samples) as part
of a GLP inspection, he/she should be aware of the techniques of sampling, procedures for identification
and custody, and the availability of subsequent storage or analysis. Directed investigations are more
likely to require sample collection than are routine compliance inspections and audits. In any event, if
physical sampling is contemplated, the supervisor should first be consulted regarding issues of authority,
analysis, and safety.
Examples of different types of situations in which an inspector may need to collect a physical sample as
evidence include:
• Test or control substances. (1) The physical appearance does not agree with the written
description in protocol, final report, or raw data; (2) a significant impurity is suspected
to have been misanalyzed in the test substance; or (3) the test substance was reported as
being technical grade, when it appears to have actually been reference grade material.
• Reference substances. There is reason to question either the stated identity or purity of
the reference substance.
• Analytical specimens,. (1) Specimens are improperly labeled and a photographic exhibit
is not feasible; (2) the actual specimens appear to differ from the matrix described in the
protocol, raw data, or the study report; or (3) there are serious concerns about the
validity of the reported findings, and analytical confirmation by EPA is feasible and
warranted.
• Slides, blocks, or wet tissues. Photographic reproduction or other documentation is not
feasible or available and (1) there is a discrepancy between the reported findings of the
facility's pathologist/toxicologist and the findings of EPA's auditor; (2) specimens are not
labeled according to GLP requirements; or (3) specimens appear to have deteriorated
appreciably due to improper archival conditions.
Since blocks or specimens will represent original materials that cannot be reliably sampled
with representativeness preserved, the supervisor should'be consulted before sampling.
An additional slide can usually be prepared from the original block, if necessary.
• Test system feed, water, soil, or bedding. (1) Unreported physical or chemical
contamination that may have affected study integrity is suspected; (2) the feed, soil.
water, or bedding does not appear to conform with the protocol, applicable SOP, raw
data, or study report, and this problem cannot be documented by other means.
3-27 September 1993
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CHAPTER THREE
• Test, control, or reference substance mixtures with carrier. (1) There are concerns or
suspicion that test or control substance mixtures with carrier are not stable over the period
of their use or that they may not have been homogeneous; (2) mixtures are suspected of
having been improperly analyzed; or (3) there is suspicion that the wrong or a degraded
test, control, or reference substance was used.
Guidance on collecting certain types of chemical samples and chain-of-custody is provided in the TSCA
and FIFRA inspection manuals. In all cases, the inspector should consider the following prior to
sampling;
• The sample is absolutely required for use as evidence and other forms of documentary
samples cannot be used or are not available.
• Means are available to properly and safely collect the sample, preserve it (if necessary),
and transport it to the testing facility or other EPA designated facility.
• Proper chain-of-custody can be initiated and maintained.
• The appropriate analyses or other evaluation can be performed in a reliable, timely, and
legally defensible manner.
Specific guidance on sampling procedures is provided in SOP GLP-S-02 (in preparation) when collecting
physical samples intended to document potential TSCA or FIFRA GLP violations.
3.8.6 Maintenance of Inspection Materials
The security of all materials resulting from an inspection must be maintained by the inspector to assure
their integrity for possible use as evidence.
These materials include, but are not limited to:
• Completed inspection forms and notification letters
• Field notebook(s)
• Document copies
• Signed statements
• Photographs
• Physical (nondocumentary) samples/specimens.
Materials must remain secure during two stages: (1) while in the inspector's possession during report
preparation and (2) after transfer to longer-term office storage or archiving. The inspector is responsible
for maintaining the master file of the original versions of documents or photographs collected during (or
in followup to) an inspection. Copies of these materials, not the originals, should be made available to
auditors for their use in preparing study audit reports. Physical samples and other evidence are also the
inspector's responsibility, particularly with respect to establishing and maintaining custody when further
analysis or evaluation is required.
GLP Inspection Manual 3-28
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iNsrecnoH PJKXZDUKXS
Most evidence collected will be in the form of data or record copies, written statements, field notebooks
and photographs — materials that can be secured by the inspector in a locked file cabinet or desk. At
a minimum, during inspection report preparation, the collected evidentiary materials should be maintained
in a secured office. Only those with a "need to know" should view the materials and then only with
knowledge of or in the presence of the inspector. Auditors are to take the same general security
precautions with copies of data and records in their possession.
Once the inspection report has been prepared, signed, and transmitted to OCM, the inspection materials
not included in the report should be placed in a longer-term evidence file along with a copy of the report,
the field notebook(s), and any other related documents. Auditors' notebooks should also be recalled and
placed in the appropriate OCM, NHIC, or Regional permanent evidence files, particularly when the
auditor is not an EPA employee or not a regular member of the GLP inspection staff.
The permanent evidence file for each office (LDIAD, NEIC, or the Region) should be organized for ease
of retrieval either by facility or chronologically (or a combination thereof). An individual should be
designated to manage the longer-term storage of evidence files to assure their completeness, retrievability,
and integrity.
3.8.7 FIFRA/rSCA Receipts
Ail evidence collected at a facility during an official inspection is to be listed or described on an
appropriate FTFRA or TSCA receipt form before the inspection team leaves the facility. All photocopied
data and records, brochures, photographs, and physical samples are to be listed. Related data and records
should be grouped together and stapled to form a document set that can be more conveniently listed on
the appropriate receipt. Each page or document set should be marked as previously described, and the
total number of pages noted on the receipt.
3.8.8 Investigations Involving Alleged Criminal Activity**
Participants in criminal investigations may be subject to additional requirements governing such
investigations. Because of the severe penalties that may be imposed on the individuals convicted of
violating the criminal provisions of the environmental laws or other statutes, there is closer scrutiny of
constitutional safeguards to protect the individual's rights. Special Agents of the EPA, Criminal
Investigations Division, will provide instructions regarding these safeguards to the project team on ail
investigations in which they are involved. From the beginning of such an investigation until it is
completed, the rights of all individuals must be fully protected.
Taken from "NEIC Policies and Procedures," August 1991, EPA-330/9-78-001-R, U.S. EPA
National Enforcement Investigations Center, Denver, CO.
3-29 September 1993
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CBAJTEK TBKES
If, during the course of a civil/administrative inspeaion, aspects of criminal activity become apparent,
the inspector should obtain all the evidence documenting the possible violation. The Criminal
Investigations Division or the appropriate Special Agent-in-Charge must then be apprised immediately.
If a criminal investigation is opened, any files will be maintained separately from the current (or planned)
civil investigation. Where applicable, EPA's policy on parallel criminal and civil enforcement
proceedings must be followed.
CLP Inspection Manual 3-30
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CLP COtCTVANCX KfYJEW
4.0 GLP COMPLIANCE REVIEW
4.1 INTRODUCTION
The compliance review is that part of the inspection in which the inspection team attempts to determine
the extent to which the facility is complying with the principles set down in the GLP regulations at the
time of die inspection. The conduct of a compliance review generally requires a walk-through of the
facility and an audit of the records and procedures of an ongoing study or recently completed study.
Depending upon the situation at the testing facility, the review may be altered, based on the needs of the
inspection team, immediate availability of the testing facility or staff to be visited, studies being
conducted, or other circumstances.
Major areas of concern include:
• Adequacy of organization (e.g., existence of an independent Quality Assurance Unit
QAU)
• Adequacy of staffing, facility, and equipment for the workload
• Completeness and adequacy of SOPs and protocols
• Adequacy of archives
• Credentials of staff to perform work as shown by curriculum vitae, training records, and
other documents
• Receipt, storage, and use of test, control, and reference substances
• Receipt, handling, care, and use of test systems
• Records of analysis for contaminants of food, water, soil, and other media.
*-
Inspectors should review the contents of relevant SOPs, such as SOP GLP-C-01, Conducting a Field Site
Compliance Inspection, for more detailed instruction on compliance reviews. The inspector should be
aware that EPA may from time to time issue new Standard Operating Procedures (SOPs). these SOPs
are the primary guidance documents developed by EPA to inform GLP inspectors of current policy and
procedures. As such, all current SOPs will take precedence over the contents of this manual. In areas
where this manual and newer SOPs differ, the directives of the SOPs will be followed.
4.2 FAOLTTY COMPLIANCE REVIEW
The inspector should examine the master schedule to select an ongoing study for use as a basis for the
compliance review. By tracking the progress of the study, the records being taken, and the compliance
of the staff with the SOPs, it is possible to evaluate the facility's current level of compliance with the
•M September 1993
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CHAPTER FOUR
GLP regulations. In addition, the inspector should examine the layout of the facility and the
organizational charts of the facility to get an understanding of the scope of the facility. This will assure
that the familiarization walk-through of the facility covers all appropriate areas. During the walk-through,
the inspection team members should identify potential areas of concern. They should discuss their
concerns and impressions with the lead inspector for followup later in the inspection.
The following information for the ongoing study being used for the compliance review should be recorded
during the inspection:
• Applicable statute
• Test substance
• Study title
• Lab project number
• Sponsor
• Sponsor representative
• Study start date
• Study director.
The inspector should select an ongoing FIFRA study for FIFRA inspections and an ongoing TSCA study
for TSCA inspections. If that is not possible, the inspector should be sure to give the facility the
appropriate notification (i.e., FIFRA or TSCA Notice of Inspection) to cover the selected study. The
areas mat should be evaluated during the facility compliance review are discussed below.
4.3 ORGANIZATION AND PERSONNEL
4.3.1 Personnel [40 CFR §160.29]
• Education, training, and experience. The inspector should determine whether facility
supervisors and staff have the education, training, and experience, or a combination of
these, necessary to perform their assigned functions. During the course of the inspection.
the inspector should also observe the actions and responses of facility personnel as
indications of whether their training and experience are appropriate. The staffs responses
to questions concerning the operation of the testing facility or the conduct of the
study(ies) observed during the walk-through can provide insight into their competence.
The inspector should note any deviations from routine testing facility practices, i.e..
spilled samples, careless analyses, dirty facilities, recordkeeping mistakes, or other
actions that show the inexperience or inadequacy of the staff. Further, the inspector
should note whether records show missing data; this may indicate that the staff is either
not attentive to details or lacks the time to record data properly.
• Personnel information. The inspector should examine the facility's summary of the job
descriptions, training records, curriculum vitae, and experience for its staff and
supervisors. This summary must be maintained and updated by the facility, and should
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GLP CoteniAncx Rxvatw
contain enough detail to show whether the qualifications of personnel meet the standards
of their jobs.
pf personnel. The number of personnel must be sufficient for timely and proper
conduct of the study according to the protocol. The inspector should compare the actual
number of personnel to the number of personnel deemed necessary by the study protocol.
The inspector should note if there are any delays in the processing of test substances, the
analyses of specimens, or the completion of reports due to insufficient staffing and/or
equipment.
• Personal ftanfotion and health. Facility personnel must take steps to prevent
contamination of test systems and substances. The inspector should observe and inquire
about the personal sanitation and health precautions used to prevent contamination of test
systems, .specimens, or substances or otherwise adversely affecting the quality of the
study. ,
•• Appropriate clothing. Facility personnel must wear clothing appropriate for the dudes
they perform. The inspector should observe whether adequate protective clothing is in
use at the time of the inspection. The inspector should also inquire about the facility's
procedures for handling protective clothing, including requirements for changing clothing
as often as necessary to prevent microbiological, radiological, or chemical contamination
of test systems, specimens, and test, control, and reference substances.
• Personnel illnesses. The inspector should determine whether precautions are in place to
exclude from the test area any individual who has an illness that may adversely affect the
study. Personnel must have been instructed to report such illnesses to their immediate
supervisor.
4.3.2 Testing Facility Management [40 CFR §160.31]
The inspector should review the management practices of the facility to determine whether they meet the
requirements of the GLP regulations.
• Designation of a study director. Management must designate a study director prior to
initiation of the study. The inspector should examine facility records to determine if they
show that a study director was designated before work began and whether the study
director has the appropriate education, training, and experience.
• Replacement of a study director. Management must replace the study director promptly
if necessary. Thus, an ongoing study that is the focus of the inspection must have a study
director in place.
• Management assurances. Management must also assure the following:
A QAU is in place as required by 40 CFR §160.35, as appropriate.
Test, control, and reference substances or mixtures have been appropriately
tested for identity, strength, purity, stability, and uniformity, as applicable.
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CHAPTER Fov*
Personnel, resources, facilities, equipment, materials, and methodologies are
available as scheduled.
Personnel clearly understand the functions they are to perform.
Any deviations from the GLP regulations reported by the QAU are
communicated to the study director and corrective actions taken and documented.
(While the inspector cannot review the findings of the QAU, the inspector can
check to determine if the findings were sent to the study director and that
corrective actions were taken. This may be done by reviewing the QAU records
that do not include QAU findings, problems or actions recommended and taken.
This may also be done by requesting management to certify that inspections are
being implemented, performed, documented, and followed up in accordance with
§160.35.
>
If the inspector finds deficiencies in any of these areas, s/he should determine whether management
failures contributed significantly to the deficiencies. Deficiencies in facility management may be
evidenced by deficiencies in other areas of GLP compliance and may be determined by considering some
of the following aspects of the study:
• Whether the facility has sufficient personnel and the organization to complete the study
in accordance with GLP standards
• Whether the QAU is independent from the individuals conducting the study
• Whether the QAU reports its findings to the study director and testing facility
management
• Whether the QAU maintains a record of the quality assurance inspections that meet GLP
requirements.
4.3.3 Study Director [40 CFR §160.33]
The study director has overall responsibility for the technical conduct of the study as well as the
interpretation, analysis, documentation, and reporting of results. The study director represents the single
point of study control. As such, the inspector must assure that the following items meet the GLP
requirements:
• Study director qualifications. The study director must have the appropriate education.
training, and experience to carry out her/his responsibilities. The inspector's review of
the facility's personnel records should provide an indication of whether the study
director's qualifications are adequate.
• Study director assurances. The inspector should determine whether the study director has
assured the following:
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CLP COtfffJAHCX
The study protocol, including any changes, is properly signed and approved (see
40 CFR 5160.120) and is followed.
r.- All experimental data, including observations of unexpected test system
responses, are recorded and verified.
Unforeseen events that may affect the quality and integrity of the study are noted
and corrective actions taken and documented.
Test systems are as specified in the protocol.
All applicable GUP regulations are followed.
All raw data, documentation, protocols, specimens, and final reports are archived
at or before completion of the study.
Problems in these areas indicate that the study director has not performed as required by the GLP
regulations.
To determine whether the study director is properly discharging this responsibility, the inspector should
obtain some basic information about how the study director operates. In particular, the inspector should
determine the level of contact the study director has with the conduct of the study through such
information as:
• The relationship of the study director to the study being conducted (i.e., level of
involvement)
• Whether the studies are conducted onsite or at another facility
• The level of contact the study director has with any work done at other facilities involved
in the study
• The frequency at which the study director reviews the conduct of the study or the
collection of data
• The availability of the study director when changes in the conduct of the study are
roqpured
• H0 process by which changes in procedures are authorized.
Also, the inspector should determine if the study director assures that data are archived in a timely
manner
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COAPTEX FOUR
4.3.4 Quality Assurance Unit (QAU) [40 CFR §160.35]
The facility must have a QAU independent from the personnel actually directing and performing the
study. The QAU is responsible for monitoring each study to assure management that the facilities,
equipment, personnel, methods, practices, records, and controls are in conformance with the GLP
regulations. The organizational chart should show that the QAU is independent from the conduct of the
study.
The inspector should verify that the QAU is fulfilling its responsibilities with respect to the conduct of
regulatory studies, but is not permitted to examine reports of QAU inspection findings and problems, or
actions recommended and taken.
The QAU is responsible for the following items:
\
• Master schedule. The inspector should obtain a copy of the master schedule and check
it for conformance with the GLP regulations. The QAU must maintain a copy of the
master schedule of all studies conducted at the testing facility, indexed by test substance,
and containing information on the test system, nature of the study, the date the study was
initiated, the current status of each study, the identity of the sponsor, and the name of the
study director.
• Maintain protocols. The QAU must maintain copies of all protocols for which the unit
is responsible. The inspector should determine whether all such protocols are readily
available, and whether they are up to date.
• Study inspections. The QAU must inspect the study at intervals adequate to assure study
integrity and maintain written records of these inspections. The inspector should examine
these inspection records to determine whether they are complete, properly signed, and
show the following:
Date of inspection
The study inspected
The phase or segment of the study Inspected
The inspector's name.
The inspector should determine if the records show adequate phase checks on ongoing
studies. The inspector should also determine whether any problems likely to affect study
integrity were brought to the attention of the study director and facility management
immediately following inspection.
• Reports to management and the study director. The QAU must periodically submit to
management and the study director written reports on the status of each study, noting
problems and any corrective actions taken. The inspector should determine that
notification of QAU findings were provided.
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CLP COUKUtKX KfYOCW
Deviations from protocols and SOPs. The QAU must assure that no deviations from
approved protocols or SOPs have occurred without proper authorization and
documentation. The inspector should interview QAU personnel and review QAU reports
to determine whether the QAU has detected unauthorized deviations. If the inspector
fJnd* any deviations during the inspection, s/he should check to see if they were
authorized.
Review fir^a! stndy report. The QAU must review the final study report to assure that
this report accurately describes the methods and SOPs actually used and that the results
in the report accurately reflect the raw data collected during the study. While an ongoing
study will probably not have reached the stage where the final study report has been
written, the inspector may check whether the QAU reviewed the report for another
recently completed study.
fiml I^Jy report. The inspector should examine a final study report, if
one is available, to determine whether the QAU signed a statement in mat report
specifying the dates inspections were made and findings reported to management and me
study director.
Required records. The QAU must maintain records of the responsibilities and
procedures, and me indexing for such records. The inspector should examine such
records maintained by the QAU (some of which were described previously in this section)
to assure mat they are complete, detailed, and accurate. The inspector may also request
that facility management certify that inspections are being performed as required in 40
CFR $160.35. (Determine this by checking, whether the records indicate periodic
inspection showing the date of the inspection, the study inspected, the phase or segment
of the study inspected, and the name of the person performing the inspection. Also
determine if one or more inspection of a phase or segment of the study was conducted
while the study was ongoing.) The quality of the data being recorded should also show
compliance with GLP regulations; where this is not the case, the QAU inspection
procedures have rafled. The inspector may also note whether the QAU appears to have
the support of test facility management
4.4 EtouriES
The inspector should take particular note of the nature of the facilities provided for the studies during the
walk-through, at mis provide* the best opportunity for assessing their adequacy.
4.4.1 TertFad»fc General [40 CFR §160.41]
The inspector stettf note whether the facility is of suitable size and construction for the proper conduct
of the studies. Functions that have me potential to adversely affect the study must be conducted in an
area sufficiently separated from other study areas to preclude these effects. The space, bench area,
storage, environmental chambers, caging, water baths, water quality and equipment, and other facilities
must be appropriate for the type of testing being conducted. The inspector should describe the size and
construction of the facility and take photographs, when appropriate.
4-7 September 1993
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CHAPTER Foux
4.4.2 Test System Care Facilities [40 CFR §160.43]
• Test system separation. The facility must have a sufficient number of rooms or other
areas for proper separation of species or test systems, isolation of individual projects,
quarantine or isolation of animals or other test systems, and routine or specialized housing
of test systems. Areas for plants or aquatic projects must comply with the requirements
found at 40 CFR §160.43(a)(l) and (2) as appropriate.
• Biohazardous areas. Separate areas must be provided for tests using biohazardous
substances or test systems.
• Areas for diseased test systems. Separate areas must be provided as appropriate for the
diagnosis, treatment, and control of test system diseases. The areas must provide
effective isolation of test systems known or suspected of being diseased or of being
carriers of disease.
• Disposal of materials. The facility must have proper facilities for collection and disposal
of contaminated water, soil, or spent materials. Waste from housed animals must be
collected and disposed of so as to minimize vermin infestation, odors, disease hazards,
and environmental contamination.
conditions. The facility must have provisions to regulate environmental
conditions (e.g., temperature, photoperiod) as specified in the protocol.
• Test system media. The facility must have an adequate supply of water (for aquatic
organisms) or soil of the appropriate composition (for plants) as specified in the protocol.
4.4.3 Test System Supply Facilities [40 CFR §160.45]
The facility must have appropriate storage areas for feed, soil, nutrients, bedding, supplies, and
equipment Storage areas for feed, nutrients, soils, and bedding must be separate from areas where test
systems are located, and must be protected against infestation or contamination. Perishable supplies must
be appropriately preserved. Test system holding and culturing areas must also be provided (i.e., ponds,
culture areas, greenhouse, holding tanks, or fields for aquatic animals or plants, as appropriate).
4.4.4 Facilities for Handling test, Control, and Reference Substances [40 CFR §160.47]
The facility must have separate areas, as necessary, for the following:
• Receipt and storage of test, control, and reference substances
• Mixing of the test, control, and reference substances with a carrier
• Storage of such mixtures.
Storage areas for test, control, and reference substances and mixtures are to be separate from areas
housing the test system. These storage areas (freezers and refrigerators in the pesticide testing facility)
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CLP ConnuNCf Ksvacr
must also be adequate to preserve the identity, strength, purity, and stability of the substances and
mixtures.
4.4.5 Tetinc Facztiry Operation Areas [40 CFR {160.49]
The facility must have adequate separation of testing facility space and other space (e.g., glassware wash
area) for the routine and specialized activities of studies.
4.4.6 Specimen and Data Storage Facilities [40 CFR $160.51]
The facility must provide archives for storage and retrieval of raw data and specimens from completed
studies and for limiting access to the archives.
4.5 EQUIPMENT
4.5.1 Equipment Design [40 CFR 5160.61]
Equipment for use in data operations and for environmental control must be of appropriate design and
adequate capacity to function according to the protocol or SOPs. The location of equipment must allow
proper operation, inspection, cleaning, and maintenance.
4.5.2 Maintenance and Calibration [40 CFR $160.63]
Equipment used in any study must be adequately inspected, maintained, and calibrated. The inspector
should confirm that SOPs adequately describe the use and maintenance of the equipment and the persons
responsible for such operations. Written records must be available to document the inspection,
maintenance, and calibration and/or standardization of the equipment, as well as any repairs resulting
from failure or malfunction. In addition, the facility's SOPs must contain detailed information on the
methods, materials, schedules, and the person(s) responsible for the performance of these activities.
The inspector should review individual records to determine compliance with the equipment requirements.
The records must provide complete and detailed documentation of inspection, maintenance, cleaning,
calibration, and repair.
-5u:r^
4.6 TtsTfl« Ittqirna OPERATION
^f.:.-'
The inspector snoefcf review the facility's SOPs as appropriate to assure they are complete, detailed, and
meet the requirements of the regulations.
4.6.1 Standard Operating Procedures [40 CFR $160.81]
• SOft. The facility must have adequate, written SOPs for at least those activities listed
in 40 CFR §160.81(b), as appropriate. The inspector should review the testing facility's
4-9 September 1993
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CHAPTER FOUR
list of SOPs, if a list exists, or the set of SOPs themselves to determine whether all
necessary SOPs are available and have the appropriate signatures. Each testing facility
area must have available the SOPs applicable to the procedures performed in the area.
The inspector should review selected SOPs, in detail, to determine if they are adequate.
The SOPs selected should be relevant to the study being used as an aid in the compliance
review, and the review should include an assessment of whether the SOPs were adhered
to or, if not, whether any deviations were properly documented.
Deviations from SOPs. Deviations from SOPs must be authorized and documented.
Significant changes to the SOPs must be authorized in writing by management. The
inspector should check for documented deviations and changes and for appropriate
signatures on the SOPs. The inspector should also note during the walk-through any
instances of the staff not following accepted procedures, including areas such as
recording of data; use of safety equipment; calibration, use, or maintenance of equipment;
handling of samples; or cleaning of animal quarters. The inspector should check these
deviations to see if they have been authorized.
Historical SOP file. The inspector should check whether the facility maintains a historical
file of all SOPs and their revisions, including dates of revisions.
4.6.2 Reagents and Solutions [40 CFR §160.83]
The containers of reagents, solvents, and solutions in testing facility areas must be adequately and
appropriately labeled to indicate identity, titer or concentration, storage requirements, and expiration date.
Deteriorated or outdated reagents and solutions must not be used. The inspector should note any
inconsistencies in labeling observed during the walk-through.
4.6.3 Animal and Other Test System Care [40 CFR §160.90]
The inspector should determine whether SOPs discussing the housing, feeding, handling, and care of
animals and other test systems exist and whether they are followed. The SOPs for test system care, as
well as actual care practices at the facility, must meet the following requirements:
• Newly received test systems must be isolated until their health status or appropriateness
can be determined.
• Test systems must not begin a study while diseased or in any other condition that might
interfere with the study. Test systems that contract such a disease or condition during the
study must be isolated. The facility must keep documents on diagnosis and treatment of
diseased test systems.
• Test systems must be appropriately identified, as required by 40 CFR §160.90(d).
• Test systems of different species, or of the same species but different studies, must be
housed separately, unless integrated housing is called for by the protocol.
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CLP
• Appropriate schedules for cleaning and sanitizing all test system holding areas must be
arranged.
• Feed, soil, and water used for the test systems must be analyzed to assure that potential
contaminants are not above levels set in the protocol, documentation of such analyses
must be maintained.
• Animal cage or pen bedding must be maintained and replaced as necessary to assure
animals stay clean and dry.
• Use of pest control materials must be documented; such materials must not interfere with
the study.
• Plant and animal test systems must be acclimated to test environmental conditions prior
to the study.
the inspector should determine compliance by interviewing study personnel and visiting facility areas
where the test system is housed. In addition, the inspector should review SOPs for the housing, feeding,
handling, and care of the test system in detail to determine if they are adequate. The SOPs selected
should be relevant to the study being used as an aid in the compliance review; the review should include
an assessment of whether the SOPs were adhered to or, if not, whether any deviations were properly
identified.
4.7 TEST, CONTROL, AND REFERENCE SUBSTANCES
4.7.1 Test, Control, and Reference Substance Characterization [40 CFR $160.105]
The inspector should examine facility records to determine whether the appropriate test, control, and
reference substance characterizations have been conducted. The identity, strength, purity, and
composition or other characteristics that will appropriately define the test, control, or reference substance
must be appropriately documented before the use of the substance in a study. The method of synthesis,
fabrication, or derivation of the test substance must be documented and the location of the documentation
specified. The solubility of the test substance, if relevant, must be determined before the start of the
study. The stability of the test substance must also be periodically determined. The test container(s) must
be adequately labeled with the name of the substance, the Chemical Abstracts Service (CAS) number, or
code oumber and batch number, expiration date, and storage conditions. Test substance containers must
be retained. For studies lasting more than 4 weeks, a reserve sample of the test substance must also be
retained. Finally, the stability of the test substance under the existing storage conditions must be known.
4.7.2 Test, Control, and Reference Substance Handling [40 CFR §160.107]
The inspector, based on observations made during the inspection, should determine whether adequate
procedures have been established for handling the test, control, and reference substances used during the
conduct of the study. Storage conditions must be adequate; distribution practices must preclude
4-11 September 199]
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CHAPTER FOUR
contamination, deterioration, or damage; proper identification of the test substance must be maintained
throughout its handling; and a use or distribution log for the test substances must be maintained.
4.7.3 Mixture of Substances with Carriers [40 CFR §160.113]
Appropriate analytical methods must be used to test each test, control, or reference substance mixed with
a carrier to determine the following: the uniformity and concentration of the mixture; the solubility of
each substance in the mixture prior to the experimental start date, if relevant; and the stability of the
mixture before the experimental start date or with each new batch. The expiration dates of any of the
ingredients in the mixture must not be exceeded. If a vehicle is used for mixing the test substance with
a carrier, evidence must be provided that it did not interfere with the integrity of the test.
4.8 PROTOCOL FOR AND CONDUCT OF A STUDY
4.8.1 Protocol [40 CFR 5160.120]
Each study must have an approved written protocol that clearly indicates the objectives of the study and
all methods to be used. The inspector should examine the protocol for the ongoing study and look for
information on the following areas:
• Description of the objectives and the methods to be used
• Identification of the test, control, and reference substances
• Name and address of the sponsor and test facility
• Proposed experimental start and termination date
• Justification for the selection of the test systems
• Description of the test systems
• Procedure for identification of the test system
• Description of the test design, including bias control methods
• Description of the diet for the test systems
• Route of exposure
• Each dosage level of test, control, or reference substances to be administered
• Type and frequency of tests, analyses, and measurements
• Records tO be maintained
• Date of'approval of protocol by study director and sponsor
• Dated signature of study director
• Statement of proposed statistical methods to be used
• All changes in or revisions to the protocol, including signatures, reasons, and dates.
4.8.2 Conduct of a Study [40 CFR 5160.130]
The study and monitoring of test systems must be conducted in accordance with the protocol. The
inspector should be familiar with the content of the protocol for the study. During the inspection, s/"he
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GLP CottruAKX KKYTKW
should attempt to document the occurrence of events reported to be already accomplished. The inspector
should ask to see either the samples taken or evidence that the samples, observations, or measurements
have been taken, handled, analyzed, or processed on schedule as described in the protocol or the
appropriate SOP. All samples must be labeled with appropriate information and handled according to
the prescribed procedures. The inspector should note anything that was atypical for the type of study
being investigated, such as:
• Test vessel size
• Amount of test substance used
• Size, number, or handling of samples used or taken
• Age of test systems
• Unusual timing of observations
• Unexpected trends in biological, chemical, or environmental data collected to date; or
distribution or handling of test systems or test substances.
Any inconsistencies in the recorded data should be noted, such as normally sequential events not being
recorded in a logical sequence, along with any failure to account for all test systems and test substances
obtained for use in the study.
The inspector should determine whether the following requirements are also met:
• Specimens. Specimens must be properly identified by test system, study, nature, and date
of collection. This information must be located on the specimen container or accompany
the container in a manner that precludes errors in data recording or storage.
• Histopathology. In studies involving histopathology, information from postmortem
observations must be available to a pathologist at the time of histopathological review.
recording Data (unless recorded in automated data systems) must be recorded in
ink, dated on the day of entry, and signed or initialed by the recorder. Any change must
not obscure the original entry, must indicate the reason for the change, and the person
responsible for the change must be identified.
4.9 RECORDS AND REPORTS
4.9.1 Reporting of Study Results [40 CFR § 160.185]
In a compliance review, this part of the GLP standards will generally not be involved. The inspector can
determine the procedures that are in place to assure the study director either obtains copies of the raw
4-13 September
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CBAPTBX FOUR
data for processing or a signed report from the staff. There should be data available to support all aspects
of the study.
By examining a recent, complete report, the inspector can determine that all pertinent required elements
are included in the report, and especially that the report includes a quality assurance statement and
statement of compliance or noncompliance for the parts conducted at the site. The inspector should check
the completed report for the date of the study director's signature and the date of the signature on the
compliance statement.
4.9.2 Storage and Retrieval of Records [40 CFR §160.190]
The facility must have storage areas for all the data, documentation, records, protocols, specimens, and
final reports relating to the studies. Correspondence and other documents relating to interpretation and
evaluation of data must also be kept. Temporary archives must be available for data being generated by
the facility during the ongoing study. A person must be designated as responsible for the archives, and
entry to the archives must be limited to authorized personnel. Material retained or referred to in the
archives must be indexed for expedient retrieval. The inspector should review the procedures the facility
follows to archive all the data for the study and the final report, and determine whether these meet the
requirements of 40 CFR §160.190, as appropriate.
4.9.3 Retention of Records [40 CFR §160.195]
The inspector should determine whether records, raw data, and specimens have been retained for the
period prescribed by the appropriate regulations. For TSCA GLP studies, records must be kept for at
least 10 years following the effective date of the applicable final test rule, except in the case of testing
under Section 5 of TSCA, for which records must be kept for at least 5 years following the date of
submission of the study results to EPA. For FEFRA GLP studies, records must be kept (1) for the period
for which a research or marketing permit is held, if the study has been used to support the application
for that permit; (2) for a period of at least 5 years following submission to EPA in support of a research
or marketing permit; or (3) in any other case, for a period of at least 2 years following termination,
completion, or discontinuation of the study.
4.9.4 Special Cauidentioas for Field Sites
Several practical considerations should be addressed by each member of the inspection team before
entering the facility and/or during the inspection. The following are some issues that the team members
should be aware of when in the field:
• Climatic conditions. In the field environment, weather conditions may vary from day to
day during the inspection. Team members should be able to accommodate the field
weather conditions within reason. Appropriate clothing, such as boots, long pants.
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GLP Cottriufcx RXYJSW
jackets, and rain gear, should be available if the weather changes. Hats, sunglasses, and
sunscreen are additional items that should be available in the field.
If the team wants to observe a critical phase of an ongoing study, such as an application
of test substance, they should be prepared for the possibility of an early morning (3 a.m.
to 7 a.m.) application window. Team members should understand that early morning
weather conditions are oftentimes more favorable to the study.
• Field safety. According to safety statistics, the fanning environment is one of the most
dangerous working environments in the United States. At the field location, team
members will most likely be in close proximity to power take-off equipment, hot
manifolds, sharp edges, hydraulic machinery, and a multitude of other types of
equipment. To avoid being injured, the team members should keep a safe distance from
these types of equipment at all times. If, for some reason, inspection of a piece of
operating farm equipment is necessary, extreme caution must be exercised, and
appropriate safety questions should be addressed to the equipment operator or other
appropriate personnel prior to conducting any equipment inspection. Loose clothing of
any type should never be worn in the field. Team members need to remain alert at all
times, and should always keep long hair, shirt sleeves, and pant legs away from
equipment.
• Indigenous animals. As one may expect, the field environment may be infested with
bugs, flies, ants, and other pests. Team members may wish to take insect repellant along
on the inspection. (Extreme caution should be exercised in the use of insect repellant [a
pesticide] in the vicinity of a pesticide study.) If a team member has a known allergic
reaction to an insect bite or sting, the team leader should be informed so that appropriate
precautions can be taken. Many times skunks, snakes, rodents, raccoons, and other
wildlife may be in the area. Team members should be cautious around these animals and
remain at a safe distance from them.
• Field data. Field data may be difficult to obtain at times at remote facilities. These data
are often forwarded to the sponsor at the completion of a study. The inspector should
contact facility personnel well in advance of the inspection and coordinate with them such
details as having data available at the site for auditing. This will help to assure that all
documents and inspection issues are covered before the team arrives at the field site.
• Test substance storage. Adequate storage conditions for test substances is commonly a
problem at many field locations. The team member who inspects this issue should know
the storage stability limits for the test substance (this is often given on the label for
registered pesticides, but otherwise should be provided by the study sponsor) and should
verify that the limits have not been exceeded. If the stability requirements, such as
temperature, have been exceeded, the inspector should be notified and appropriate
documentation should be obtained.
• Weather data. The study protocol and/or SOPs usually specify that weather data be
collected periodically, especially during the test substance application phase of the study.
The auditor should verify that this has been done and should compare site records with
the protocol and study report. Any discrepancies should be noted and documented, and
the inspector should be advised.
4-15 . September 1993
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CHAfTEX FOUR
aple storage and transfer. These areas are of critical importance to the
conduct of most studies. Facility SOPs and the protocol should be carefully reviewed and
compared to sampling data to determine if the functions were in fact carried out by
- facility personnel accordingly. Typically, samples have not been monitored according to
protocol or facility SOP requirements, which may then lead to distorted results by the
analytical laboratory.
• Test and control plot histories. Most field cooperators have very extensive plot histories
(previous crops, cultural practices, and pesticide usage) for their own property. When
a contractor/cooperator leases property from a local farmer, these histories may not exist
or the cooperator may not have asked for them. The team member should verify the plot
histories of all study plots, including the control plot(s), and note any absent or sketchy
plot histories.
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AUDIT PXOCSDUXEt
5.0 AUDIT PROCEDURES
5.1 INTRODUCTION
The purpose for conducting audits of studies submitted to EPA under FTFRA or TSCA is to assure the
integrity and reliability of the study data. In evaluating the quality of the study data, the auditor must
verify that, where applicable, the data were generated in compliance with GLP regulations (40 CFR Parts
160 and 792, respectively). In addition, the auditor must determine if (1) all of the data have been
retained, (2) the study can be reconstructed from the data, and (3) the study findings and conclusions are
supported by the raw data, including any data that were not considered while drawing conclusions. The
study audit is normally accomplished through the completion of the following activities:
• Review of available raw data, records, and reports
• Interviews with study personnel
• Review of testing facility operations and practices.
5.2 GLP COMPLIANCE
In addition to the GLP compliance review (see Chapter 4), the auditor and/or inspector must determine
that all studies being audited were conducted in such a manner as to comply with GLP regulations and,
if not, document such deficiencies:
• FIFRA. Effective October 16, 1989, 40 CFR Part 160 is applicable to "studies which
support or are intended to support applications for research or marketing permits for
pesticide products regulated by the EPA. This part is intended to assure the quality and
integrity of data submitted pursuant to sections 3, 4, 5, 8, 18, and 24{c) of FIFRA...'
A study is defined in 40 CFR §160.3 as "any experiment... in which a test substance is
studied ... to determine or help predict its effects, metabolism, product performance
(efficacy studies only as required by 40 CFR §158.640), environmental and chemical fate,
persistence and residue, or other characteristics in humans, other living organisms, or
media. The term 'study' does not include basic exploratory studies carried out to
determine whether a test substance or test method has any potential utility."
Prior to October 16, 1989, but on or after December 29, 1983, 40 CFR Part 160 was
applicable only to "any in vivo or in vitro experiment in which a test substance is studied
... to determine or help predict its toxicity, metabolism, or other characteristics in
humans and domestic animals. The term does not include studies utilizing human subjects
or clinical studies or field trials in animals. The term does not include basic exploratory
studies carried out to determine whether a test substance has any potential utility or to
determine physical or chemical characteristics of .a test substance."
• TSCA. Effective September 18, 1989, 40 CFR Part 792 is applicable to "studies relating
to health effects, environmental effects, and chemical fate testing. This part is intended
to assure the quality and integrity of data submitted pursuant to testing consent
agreements and test rules issued under section 4 of TSCA..." A study is defined (§792.3 •
5-1 September /'?«<
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CBAPTEX FTVB
as "any experiment... in which a test substance is studied ... to determine or help predict
its effects, metabolism, environmental and chemical fate, persistence, or other
characteristics in humans, other living organisms, or media. The term 'study* does not
include basic exploratory studies carried out to determine whether a test substance or a
test method has any potential utility."
Prior to September 18, 1989, but on or after December 29, 1983, 40 CFR Part 792 was
applicable only to "studies relating to health effects, environmental effects, and chemical
fate testing. This part is intended to assure the quality and integrity of data submitted
pursuant to section 4(a) of TSCA." A study is-defined (§792.3) as "any in vivo or in
\itro experiment in which a test substance is studied ... to determine or help predict its
fate, toxicity, metabolism, or other characteristics in humans, other animals and plants.
The term does not include studies utilizing human subjects or clinical studies. The term
does not.include basic exploratory studies carried out to determine whether a test
substance has any potential utility."
Therefore, not all studies that may be audited by EPA were required to be conducted in compliance with
GLP standards. Thus, the auditor must first determine which, if any, GLP regulations apply to the
study(ies) that s/he will be auditing. This should be done as early in the inspection process as possible.
If there is any uncertainty about the applicability of the regulations to a study, the auditor should contact
the inspector or the Chief, SSB, LOIAD, for assistance in making the determination.
If it is determined mat a study was not required to be performed in accordance with GLP standards, then
this portion of the study audit need not be conducted. The FIFRA study audit will then consist primarily
of a data reliability review and the determination that all original raw data have been retained for studies
involving registered pesticides regulated by 40 CFR §169.2(k), Books and Records.
LDIAD SOP GLP-C-02 describes in detail standard procedures to be used for determining the compliance
of studies with respect to the GLP regulations. This SOP was written for nonhealth effects studies, but
the basic principles are applicable to all studies. The auditor should be familiar with this SOP before
attempting to audit the GLP compliance of a study. Additional guidance and assistance should be
available from the inspector.
The following GLP-related topics may be evaluated for each study:
• Compliance statement
• Study director
• Quality assurance role
• Master schedule
• Facility environmental information
• Test system information
• Test chemical information
• Equipment logs
GLP Inspection Manual 5-2
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AUDIT PXOCZDUKES
• SOPs
• Personnel qualifications
• Protocols and approved changes or revisions
• Receipt information
• Archives.
If a GLP review is to be conducted as part of the study audit, the auditor should review the study report
before entering the facility to ascertain that it contains all applicable elements required by the GLP
regulations. Additionally, the auditor should also review the study protocol and deviations for each study
during the audit to determine adequacy of, and compliance with, the protocol.
During the review of the data, the auditor should determine if the study was conducted as described in
the protocol and its approved changes or revisions, and if documentation is available to demonstrate that
the study director was notified of, and approved, any deviations from the signed protocol.
The auditor should also determine if the personnel involved in the study were qualified and adequately
trained, and mat the facilities and equipment were of appropriate size, design, and capacity to function
according to the protocol. To accomplish this, personnel training records, facility floor plans, and
equipment maintenance and calibration records for the time that the study was conducted should be
reviewed as part of the audit. For detailed information on review of these elements, the auditor should
refer to Chapter 4.
In conducting a study audit, the auditor will be reviewing and verifying all the same elements as in the
compliance review. However, the SOPs reviewed will be the ones in place at the time of the study,
rather than the SOPs currently in place (as in the case of a compliance review).
Study auditors should review the required report elements, described in SOP GLP-C-02 to familiarize
his/herself with all the information necessary to complete the audit. This information should be recorded
in the auditor's field notebook for reference when writing the report.
5.3 DATA REVIEW •
A number of different techniques may be used to determine the integrity and reliability of study data and
study reconstructafailfty. During the review of the study report and before entering the facility, the
auditor should develop the approach that s/he will use.
A useful approach is to follow different aspects of the study (test substance application, specimen
analysis) chronologically. For example, in a typical study the auditor can: .
5-3 September 199J
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COAPTEX
• Trace the test substance from receipt through characterization (if done by the facility),
storage, distribution, and application to the test system, checking all data and records in
a systematic fashion.
• Check any data and records of analyses to determine the stability and uniformity of
mixtures of test substance with a carrier, such as feed mixtures used in toxicology or
metabolism studies.
• Review procedures for sampling and shipment of the specimens to a testing facility for
analysis.
• Review records of storage and transfer of the specimens and of receipt, storage, and
distribution by the analytical testing facility.
• Review any method development or method validation and audit data for the actual
specimen analyses.
During an audit, the auditor needs to determine the percentage and number of data points that should be
audited. Those will depend largely on the amount of data and any problems subsequently encountered.
For a small study, it is usually desirable to audit most or all of the data points; for a large study, the
auditor may be able to assess data quality and integrity after auditing as little as 10 to 15 percent of the
data. However, if data quality problems are encountered, the auditor should increase the number and
percentage of data points audited to determine how widespread any data quality problems are. In some
cases, it may be necessary to audit all data, or all data of a single type, even for very large studies.
The auditor should assure that raw data were properly and promptly recorded, and that study data are
accurately reflected in the inspection report. The auditor should be especially careful to review any data
generated but, for one reason or another, not incorporated into the final report. The facility should have
a valid and defensible reason for rejecting or not including data, especially when the results do not
support the study conclusions. A description of all circumstances that may have affected the quality or
integrity of the data shall be included in the final report.
Study reconstructability means that sufficient records and raw data are present to allow the auditor to fully
trace the procedures, operations, specimen analyses, calculations, and data analysis and evaluation used
to produce the final study report. The data and records that are reviewed as part of a study audit should
be complete enough to permit this reconstruction. If the study cannot be reconstructed, the auditor should
determine whether the data were never recorded or whether data were simply not retained. The inspector
should then be advised so that the proper documentation can be obtained.
When deficiencies involving data quality, integrity, or retention are encountered, it is essential that they
be adequately documented and that proper evidence be collected to support any potential enforcement
action. The auditor should refer to Chapter 6 for detailed procedures for collecting documentary samples
CLP Inspection Manual 5-4
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AUDIT PXOCZDUJtB
If there is any doubt regarding documentation of potential GLP violations or other data problems, the
inspector should be consulted.
5.4 COMMON DEFICIENCIES
Common deficiencies in the study report include, but are not limited to, the following:
• Lack of study director's signature
• Failure to provide the name and address of each unit (e.g., all field sites, processing sites
and testing facility sites) of the facility performing the study
• Inadequate or missing quality assurance statement
• Inadequate or missing compliance -statement
• Failure to provide the name of the study director and/or names of other scientists,
professionals, and supervisory personnel involved in the study
• Lack of the signed and dated reports of individual scientists or other professionals
involved in the study, including those who conducted an analysis or evaluation of data or
specimens from the study after data generation was completed.
Common deficiencies in the study protocol include, but are not limited to, the following:
• Incomplete description of experimental design (e.g., failure to disclose or reference all
methodologies)
• Failure to adequately execute changes or revisions to, or deviations from, the signed
protocol
• Failure to identify the study director or lack of the study director's signature.
5_5 GUIDELINES FOR AUDITING STUDIES
Auditors conducting data audits should have and be familiar with all appropriate GLP program SOPs.
These SOPs are intended to provide specific guidance. A list of SOPs is give on page 5-6.
5.6 SOP REFERENCE LIST
The following is a list of the SOPs that EPA has developed to provide guidance in conducting compliance
reviews and study audits. All study auditors are encouraged to familiarize themselves with the
appropriate SOPs before conducting an audit. This is the list of SOPs as of the effective date of this
Manual. Inspectors and auditors have a responsibility to keep an updated, current list of relevant SOPs.
5-5 September 1993
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CHATTEX Frvs
GLP-C-xx
GLP-C-01 CoDducting a Field Site Compliance Inspection. 10/01/90
GLP-C-02 Determining Compliance of Audited Studies with GLP Requirements. 10/01/90
GLP-D-xx
GLP-DA-01 Auditing Field Studies (Analytical Chemistry). 02/01/91
GLP-DA-04 Auditing Residue and Environmental Fate Studies (Field Portions). 01/01/91
GLP-DA-06 Auditing Efficacy Studies. 06/15/91
GLP-DA-07 Auditing Nature and Magnitude of the Residue in Livestock Studies (Biology Portions).
06/15/91
GLP-S-xx
GLP-S-01 Preparation of Standard Operating Procedures. 10/01/90
GLP-S-02 Evidence Requirements for Documenting GLP Standards and Study Audit Deficiencies.
01/15/91
GLP-S-03 Format of GLP Inspection/Data Audit Summary Report. 06/16/91 (To be replaced by
GLP-S-07)
GLP-S-04 Format of GLP Inspection Comprehensive Report. 04/01/91
GLP-S-05 Glossary of GLP Terms. 01/01/91
GLP-S-06 GLP Inspection Review Committee (GRQ Procedures. 12/01/90
GLP-S-07 Format of A Brief GLP Inspection Report. (Pending)
GLP Inspection Manual 5-6
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Posr-lterecnotf Acnvrnss
6.0 POST-INSPECTION AcnvmES
6.1 INTRODUCTION
EPA inspectors conduct compliance inspections to verify that the regulated community is complying with
the FIFRA and TSCA GLP regulations. In addition, regulatory studies that have been submitted (or that
are intended for submission) to EPA are audited to verify that reported findings and conclusions are
consistent with the raw data and other supporting records, reports, and correspondence for the studies.
The effectiveness of any GLP compliance inspection depends on many factors, including the thoroughness
of the inspection, the evidence collected by the inspector, and the cooperation of the facility being
inspected. Also critical to the success of the inspection are three steps that follow the inspection:
• Conducting necessary followup activities (Section 6.2) at the conclusion of the inspection
• Ensuring the proper collection and accountability of all evidentiary material (Section 6.3)
• Preparing the inspection report (Section 6.4).
The sections that follow include a discussion of followup activities, evidence collection, and report
preparation. Followup activities assure that any outstanding documents pertaining to the facility and the
inspection are obtained as soon as possible after the inspection for evaluation and inclusion in the
inspection report. All GLP deviations and other potential violations must be properly documented so that
enforcement and regulatory actions can be successfully initiated and prosecuted. The primary function
of the inspection report is to record the events and observations of the inspector, serving as a basis for
any enforcement or regulatory decisions will be based.
6.2 FOLLOWUP
At the conclusion of the onsite phase of a GLP compliance inspection at a test site, additional activities
will be required, these include complying with the instructions to the inspector that appear on the
Investigation Request, acquiring additional information and preparation of the inspection report.
Preparation of the inspection report is most important since this will serve as the basis for any
enforcement action. However, there may also be a need to acquire additional information. such as copies
of documents and/or written statements either from the inspected test site or another facility having
information or records pertaining to studies audited or reviewed at the site of the inspection.
The purpose of this discussion is to provide guidance to the inspector on the acquisition of additional
evidentiary materials to:
• Adequately support a potential enforcement action
• Provide justification for additional inspections at other facilities
• Satisfactorily resolve issues left unanswered during a test site inspection.
6-1 September
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CHATTEX SDC
Study auditors are obligated to become familiar with the procedures described herein to assure consistency
throughout the GLP inspection program. The basic procedures described are the same for FIFRA and
TSCA, except that each statute's particular CBI procedures must be followed, as appropriate.
6.2.1 Followup Information from an Inspected Facility
At the conclusion of the onsite phase of a GLP inspection, an inspected facility may need to provide
additional documents, information, or other evidentiary materials to allow an inspector to complete the
inspection report. Examples of such documents may include, but are not limited to:
• Signed statements from facility officials regarding GLP or data issues or circumstances
related to inspection findings
• Copies of additional pertinent records, data, correspondence, or other documents that are
located by the facility after the inspection team departs
• Additional document copies or information requested by the inspector after the inspection
when further review of collected information or records by a member of the inspection
team indicates such information is needed
• Copies of data, records, or other documents routinely available from another facility of
the same company (e.g., test, control, or reference substance characterization data;
stability information; test system source records)
• Voluntary written statements by staff of the inspected facility in response to findings and
recommendations presented by the inspection team during die closing conference.
The need for these additional documents may arise (1) from discussions or agreements during the closing
conference; (2) as a result of a request from the inspector after return to his/her office; or (3) from the
test-facility locating additional materials on its own initiative. In the latter two cases, submission of
additional materials will usually be preceded by a telephone call between the inspector and the facility
regarding the nature of the materials and the most appropriate means of identification and transmittal.
Regardless of the situation, the following procedures must be considered for any followup information
or document copies submitted or requested:
• A reasonable deadline should be agreed upon for any additional information, written
statements, or document copies that the inspector requests from the test facility at the
closing conference or in a request letter.
• Subsequent to the onsite phase of the inspection, any request by the inspector for
additional information, document copies, or written statements may be made verbally or
in writing, depending on the significance or complexity of the material requested. The
written request may be made by the inspector, a staff attorney, or senior program official
as local procedural protocol dictates. The auditor, however, should never contact an
inspected facility directly to acquire additional information or documents.
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POST-INSPCCTION AcnvmES
• All requested documents, information, or written statements are to be transmitted directly
to the lead inspector; it will be the inspector's responsibility to assure that the master file
of exhibits is maintained and that appropriate photocopies are distributed to the auditors,
to LDIAD, or included in the inspection report.
• If photocopies of data (raw or transcribed), correspondence, records, or other followup
materials are to be submitted, the facility should certify, either individually on each copy
or via signed statement, that such documents are exact or true copies.
• If copies of the followup documents represent raw data as defined by 40 CFR § 160.3
(FIFRA) or 40 CFR §792.3 (TSCA), a responsible official from the test facility should
submit a signed statement as to where the original documents were located, particularly
if they were required to have been archived and did not appear to be available in the
archives when reviewed during the study audit portion of the inspection.
• Receipt of any documents or other materials received from an inspected test site or other
facility subsequent to -the onsite phase should be acknowledged by the inspector either
with an additional FIFRA or TSCA receipt form (see Section 2.8) or by a short letter
identifying the materials received.
• In general, the materials submitted by the test facility, whether data or record copies,
written statements, or other documents, should be handled according to the evidence
requirements given in Section 6.3.
An example of a request letter is given in Appendix C. In addition to providing details regarding the
materials or information requested, an ability to claim such information as FIFRA or TSCA CBI should
be discussed, as appropriate.
The inspector should include all information gathered after the completion of the inspection in the
inspection report if it supports and documents the inspection report's findings. All information gathered
during or after the completion of the inspection not included in the inspection report should be included
in the appropriate evidentiary file.
6.2.2 Followup Information from a Non-Inspected Facility
Occasionally, the inspector may need to contact a facility owned or operated by another company to
gather additional information or documents related to a particular FIFRA or TSCA GLP inspection. It
may or may not be a test site. Usually, the second facility will be a test site or office associated with the
sponsor or registrant, although it also could be a study management firm, another contract facility or
nonprofit research institution. The need for additional information or documents usually relates to test.
control, or reference substance characterization or stability. However, issues related to specimen analysis
and evaluation may also require additional supporting information or raw data copies, particularly if there
are specialty analyses involved or specimen stability is in question.
6-3 September. 199}
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COAfTER SIX
Although the primary test site (the inspected facility) may volunteer to acquire the needed materials or
information for the inspector, it is recommended that the inspector communicate directly with the other
facility. After the inspector returns to the office, the second facility should be contacted in writing
regarding the need for document copies or information. Depending upon the followup procedures, the
letter may be sent by the inspector, a staff attorney, or other senior program official. The person.
contacted at the second facility should be the study director or management official identified in the study
report or as identified by officials at the second facility. The inspector should contact the facility in
writing to request the needed documents or information; however, the inspector may wish to telephone
facility personnel first to explain the situation and advise them that the official written request is being
sent.
If the requested materials are incomplete or have significant GLP or other apparent reliability problems,
an official GLP standards inspection may be warranted at the secondary facility to fully document a
suspected violation or other problem. In such cases, die inspector's supervisor should be consulted and
an inspection arranged through the LDIAD office. The details regarding the scope of the inspection and
the specific personnel involved will be contingent on the circumstances involved and the facility's
location.
6.3 THE INSPECTION REPORT
The purpose of an inspection report is to present a complete and factual record of the inspection process
from opening conference, through the inspection, to closing conference. The report should contain
enough information about the facility and the inspection (as well as observations made during the
inspection) to enable Case Development Officers (CDOs) to make enforcement decisions pertaining to
the inspected facility and to develop a case, as necessary. .
The inspector should prepare the inspection report as soon as possible following the inspection. EPA
recommends that the report be completed within 60 days of the inspection; however, the actual amount
of time will depend on obtaining any additional required information in a timely fashion. This timeframe
should allow the inspector sufficient time to conduct necessary follow-up and to append to the report (and
mention in the narrative) any data obtained during follow-up.
As the inspector prepares the report, s/he should have the following objectives in mind:
• To include in the report all of its basic elements, ensuring that the report not only contains copies
of relevant forms and documents as appendices, but that the narrative component of the report
references those forms and documents
• To substantiate with as much evidence as possible each potential violation of FIFRA or TSCA
GLP Standards violations, again ensuring that any documents and/or photographs are not only
appended to the report, but are referenced in the narrative component of the report. (This is
necessary so that CDOs know how the data relates to the inspection.) .
GLP Inspection Manual 6-4
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• To write the report in clear and concise language
• To present factual and accurate information pertaining to all steps in the inspection process from
opening to closing conference and follow-up
• To make only those observations that are based on firsthand knowledge of the facility since
enforcement personnel must be able to depend on the accuracy of all information
• To include only information that is relevant to the facility and its compliance with FIFRA or
TSCA. (Irrelevant facts can interfere with enforcement decisions.)
The inspection report should not, under any circumstances, include the inspector's conclusions regarding
compliance or noncompliance. Conclusions should be contained in a separate memorandum or other
format that is clearly separate from the inspection report. The reason for this is that in an enforcement
case, the entire inspection report is subject to discovery by the opposing side. If conclusions of law or
opinions are in the report, it may weaken the inspector's credibility by suggesting bias. In addition, the
inspector may have been wrong about one or more violations and EPA did not pursue them. This would
be revealed through discovery and would again weaken the inspector's credibility. A separate
memorandum of findings or conclusions will usually be protected from discovery based on attorney-client
privilege or another exception rule.
6.4.1 Elements of the Inspection Report
There are certain elements that should be contained in each inspection report to ensure that necessary
information is not inadvertently overlooked. The report should always contain enough information so
the reader can determine:
• Specific reason for the inspection
• Participants in the inspection
• Compliance with all required notices, receipts, and other legal requirements
• Actions taken (and chronology)
• Statements, records, physical samples, and other evidence obtained
• Observations made
The inspection report should be a concise and chronological account of observations made and activities
undertaken during the inspection, from opening conference to closing conference and follow-up. The
field logbook and/or an inspection checklist (if used) are useful tools for developing the narrative. These
tools can help the inspector recall and include in the narrative important details concerning the inspection.
The inspector should also include the reason for the inspection, any relevant historical information, and
any knowledge of prior violations obtained during the pre-inspection process.
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COAfTEX SIX
Administrative Exhibits
Exhibits to the inspection report should include all evidence, including affidavits, statements, drawings
and maps, mechanical recordings, printed matter, and photographs, that supports the observations made
during the inspection (and which should be described in the report narrative, as appropriate). The
inspector should prepare an index of exhibits listing the name and the location of each exhibit. This index
should precede 'the exhibits and serve as a reference for enforcement personnel.
There are several forms pertaining to the inspection that should be labeled as exhibits and appended to
the end of the inspection report. The most important of these are the forms relating to the FIFRA or
TSCA inspection. They should be labeled and attached to the report as follows:
• FIFRA or TSCA Notice of Inspection
• Receipt for Samples and Documents
6.4.2 Inspection Checklists
Inspection checklists are considered to be an extension of the field notebook and are designed to collect
standard, reviewable information about an inspection. These forms, however, are only one aspect of the
full inspection and are not considered sufficient documentation for the inspection by themselves. They
should be completed during the course of an inspection and simply function as guides to ensure that all
basic data are collected. If individual items on the forms need clarification or elaboration, the inspector
should record it in the field logbook.
6.4.3 CBI Considerations
Some or all of the data gathered during the inspection may be confidential business information (CBI),
if properly claimed as such by the facility. Otherwise, the report may be released to the public in
response to a Freedom of Information Act (FOIA) Request, unless the report falls under a FOIA
exemption. Therefore, if the inspection report contains CBI, those portions of the inspection report must
be treated in accordance with FIFRA CBI procedures. However, the inspector may refer to CBI material
in general terms (e.g., by a reference number assigned by the inspector) so that the report need not be
treated as CBI.
6.4.4 Practical Tip* for Report Preparation and Writing
The style of inspection reports should be clear, concise, accurate, factual, fair, complete, and logical.
The report must be written to eliminate the possibility of erroneous conclusions, inferences, or
interpretations. It will become part of the permanent records for the facility, along with the inspector's
field logbook, samples, formal statements,' photographs and other pieces of evidence. A well-written
report will serve as a summary of these other records.
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POST-INSPECTION AcnvmES
In general, four rules apply to preparation of good inspection reports:
• Write what the reader needs to read, not what you need to write.
• Write to express, not to impress. Only facts and evidence that are relevant to the
compliance situation should be included.
• Keep the report simple. Complicated matters should be organized and stated in simple,
direct terms.
• Keep the reader in mind. Writing, language, and terms used should be familiar to the
reader. .
Keeping these three rules in mind, these basic steps should be followed when preparing to write the
inspection report:
• Review the information. As the first step, all information gathered during the inspection
should be collected and reviewed, including inspection report forms and checklists. The
inspector should then review the information for relevance and completeness. If gaps are
identified, follow-up telephone calls can be made or, if necessary, a follow-up inspection
can be conducted.
• Organize the material. There are several different methods that can be used for
organizing the inspection data. Whatever the method, the material should be presented
in a logical, comprehensive manner and organized so it can be easily understood.
• Reference accompanying material. All evidence (e.g., copies of records, analytical
results, photographs) that accompany the report should be clearly referenced so the reader
can locate them easily. All support documents should be checked for clarity prior to
writing.
In writing the report, the procedures used in, and the findings resulting from, the evidence-gathering
process should be recorded in a factual manner. The report should refer to routine procedures and
practices used, and describe in detail the facts relating to potential violations and discrepancies, but not,
as emphasized above, suggestions or conclusions that there may be or are potential violations. The
inspector should use the field logbook as an aid to writing the report.
A well-written, effective inspection report has several essential characteristics. By keeping these
characteristics in mind when writing, the end result should be a report that provides sufficient data for
proper enforcement decisions. The following characteristics, individually, will not ensure a good report.
but when addressed together throughout the complete report, will lead to an effective document that can
be used as the basis for enforcement actions:
• Fairness. The reports must be entirely objective, unbiased, and unemotional. Distortion.
rumors or gossip, or offensive remarks or language should be avoided.
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COAPTEX SIX
Accuracy. The information should be stated precisely and accurately in plain language.
The facts should be presented so clearly that there is no need for conclusions or
interpretations.
Completeness. All information that is relevant should be included. Completeness implies
that ail the known facts and details have been reported, either in the text or in an exhibit.
The report should be tested to ensure that it answers the questions "who, what, how,
when, where, and why" related to the compliance situation:
On first mention, all individuals should be called by their first, middle, and last
names
Clearly indicate what happened or how it happened
Identify the location of the occurrence as a definite place
State why a situation is particularly significant with respect to violations.
Sources. The sources of evidence should always be provided. The report should be
interview-oriented (i.e., report statements made by interviewees).
Conciseness. Elaborate or unessential information should not be included. Sentences,
paragraphs, and tables should be as short as possible.
Clarity. The inspector should minimise the possibility of misinterpretations . Thoughts
should be arranged logically and convey the desired message.
The inspector should organize the report with a logical and coherent order
in the presentation of facts.
CLP Inspection Manual 6-9
-------
APPENDIX A
COMPLETED NOTIFICATION LETTER
-------
\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
9 WASHINGTON. D.C. 20460
' OFFICE OF'
PREVENTION. PESTICIDES AND
FAX AND EXPRESS MAIL rox,c SUBSTANCES
CONFIRMATION OF RECEIPT REQUESTED
Ms. Ann L. Donargo
Sample Test Facility 000123
Main St.
Alexandria, VA 22314
Dear Ann L. Donargo:
This will inform you that the United States Environmental
Protection Agency (EPA) will conduct a Good Laboratory Practice
(GLP) inspection at your facility under the Federal Insecticide
Fungicide and Rodenticide Act (FIFRA).
The inspection will be conducted on February 14-17, 1987. The
inspection will be led by Arunas K. Draugelis. The inspection team
will review your facility's compliance status with the EPA FIFRA
GLP regulations at 40 Code of Federal Regulations (CFR), Part 160
and will audit those aspects of the studies listed in Attachment I
that were performed by Sample Test Facility 000123.
In addition, the inspection team will choose one or more
completed or ongoing studies from your Master Schedule for audit.
The purpose of the study audits is to validate data in final
reports which have been presented to the EPA in support of a
registration or marketing petition under FIFRA.
The purpose of the compliance review is to determine that the
GLP regulations of •FIFRA are being observed in your testing
facility's current procedures and practices for pertinent studies
being conducted.
Pleasa note that under FIFRA GLP regulations at 40 CFR
160.15(b) EPA will not consider reliable for purposes of supporting
a FIFRA application for a research or marketing permit, any data
developed by a testing facility that refuses to permit inspection.
To successfully conduct our inspection, we request that the
following matters be addressed prior to our arrival at Sample Test
Facility 000123
Recycled/Recyca:
O\ Pnnt»o wnn Soy/Cj^-.
-------
Please maJce available suitable space for the team. Please
have available and in good order all original data needed to verify
the final report of each study, along with full copies of the
protocol (including protocol amendments) and all reports submitted
by your facility to the study sponsors. All current personnel who
were associated with these studies should be available for
discussion with members of the team as necessary. The inspection
team will need for review copies of all Standard Operating
Procedures (SOP) documents in use at the time of study.
We will require very specific information at your facility
regarding the analytical reference standards (reference substance) .
This includes, but is not necessarily limited to, the source and
lot number, analysis for purity and identification record of
receipt and storage, test substance inventory logs and custodial
procedures for each reference substance. Records and data should
also be available to document the synthesis, radiochemical purity
and specific activity of any radio-labeled test or reference
substance used at your facility for the conduct of the studies
being audited.
In addition, where applicable, please have available any data
generated at your facility to verify or validate methodology, for
quality control, to establish storage stability, or other related
and pertinent analysis.
Please obtain from the sponsor a statement indicating the
origin of the test substance, namely, if it was sampled from the
batch for contemporary commercial use or was synthesized or
manufactured for the specific study for which the raw data are
being audited. In either case, chemistry data also include all
data to prove the identity and purity of the test substance, the
identity of any and all impurities- detected by the sponsor or
manufacturer, and data to prove storage stability of the test
substance during the lifetime of the study.
If there are any questions arising from this notice please
feel free to call Francisca Liem, Chief, Scientific Support Branch
directly. Under ordinary conditions the dates selected for the
inspection will not be changed. Ms. Liem may be reached by
telephone during regular hours at (703) 308-8333 or by fax at (703)
308-8285. ' .
Sincerely,
David L. Dull, Director
Laboratory Data Integrity
Assurance Division
Office of Compliance Monitoring
-------
APPENDIX B
INVESTIGATION REQUEST
-------
APPENDIX B
INVESTIGATION REQUEST
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION. PESTICIDES AND
MEMORANDUM TOXCSUBSTANCES
SUBJECTS Investigation Request: Sample Test Facility 000123
7ROM: David L. Dull, Director
Laboratory Data Integrity Assurance Division
TO: Ricfc Dreisch, Chief
Central Regional Laboratory
Annapolis, MD
Region III
It is requested that a Good Laboratory Practice (GLP)
Inspection be conducted as described below:
Statute: FIPRA
Type: Neutral Schema
Dates: February 14-17, 1987
Facility: Sample Test Facility 000123
Main Street
Alexandria, VA 22314
Contact: Ann L. Donargo Phone: (703) 555-1212
Lab/PDMS No.: 000123 Investigation ID: 8720001231
It is confirmed that the inspector assigned will be:
Arunas K. Draugelis
The inspector should contact the other participants listed
below to coordinate travel and accommodation arrangements:
Andrea Blaschka, HQ/OPPT
Arnold Cytryn, FDA
GLP compliance review:
An important activity during this visit will be the GLP
compliance review, which should focus on ongoing studies.
eoman»«lHM»
-------
Study audit:
EPA inspectors will conduct study audits. The study reports
listed in Attachment I are eligible for audit.
In addition, a completed study will be selected from the
master schedule for audit.
Inspection Coordination;
The inspector will deal with all administrative aspects of
this inspection, and will prepare the inspection report.
Reporting;
An Inspection Report of this inspection prepared as per SOP
No. GLP-S-03 is due at the office of the Chief of Scientific
Support Branch (SSB), Laboratory Data Integrity Assurance Division
(LDIAD) within four veefcs after the conclusion of the inspection
itself. The 6LF compliance statement, final study report pages
where the study dates are indicated and the cover page of the final
study report should be submitted as part of the Summary Report.
Notification of the Testing Facility;
This office will contact the testing facility in advance of.
the inspection date. The Inspector may contact the testing
facility as needed after the notification is made.
Please feel free to call Francisca Liem (703-308-8333) if we
can be of further assistance.
IMPORTANT NOTE TO INSPECTOR
At the conclusion of the inspection the inspector must
complete Attachment I to indicate any change in facility, address,
contact person, dates, participants, studies audited, ongoing
and/or completed studies selected at the testing facility. This
form is critical to LDIAD's ability to maintain complete records
and generate complete report's of program activities. Please sign
and mail to Chief, PSCRB at LDIAD as soon as- you return to your
home base.
cc: Francisca Liem
Robert Zisa
Arunas K. Draugelis
Andrea BlaschJca
Arnda Cytryn
-------
- 4-
Lab.
Address
Talaphona No.
Contact parson
Type of Inspection
Test substance
Attachment I
Inspection date*
Study
Lab. Pfoiaet No.
OECD Code Audit Completed Y/N
Ongoing study/studies selected: yes / no
Additional completed study/studies selected: yes / no
Comments:
Inspector:
Print name
Date:
-------
APPENDIX C
EXAMPLE OF REQUEST FOR FURTHER INFORMATION LETTER
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D.C. 20460
OFFICE OF
PREVENTION. PESTICIDES AND
TOXIC SUBSTANCES
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Dr. Janes Q. Alchemist
Senior Research Chemist:
D & H Chemicals, LTD.
Post Office Box 9999
New York, NY 22222
Dear Dr. Alchemist
On February 14-17, 1987, Arunas K. Draugelis, an inspector of
the United States Environmental Protection Agency (EPA) conducted
a Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Good
Laboratory Practice Standards (GLPS) inspection at Sample Test
Facility 000123, Main Street, Alexandria, VA 22314. As part of
this inspection Dr. Draugelis conducted an audit of the following
completed studies:
Chronic EFFECT OF AC 243,997 to the Water Flea (Daphina
Magno) in a 21-day Flow-through Exposure.
Testing of AC 243,997 through FDA Multi-Residue Protocols
A through E
These studies were submitted to EPA by D & H Chemicals, LTD. in
partial support of a pesticide registration for AC 243,997 under
the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).
During Dr. Draugelis review with the Sample Test Facility
000123 staff, some raw data could not be located at the facility.
The raw data regarding the analytical identification,
characterization and stability of AC 243,997 were missing. Please
send certified photocopies of the following information for the
test substance to Francisca Liem,.Chief of the Scientific Support
Branch at the address specified in this letter:
>_7 Recycled/Racy dace
PnntM wltn SoyiCarc J -•
cem»m» it ie«tt SO'-. •«•-.
-------
Documentation substantiating the identity, purity
and characteristics of AC 243,997. Such
. documentation may include true copies of lab
notebook entries, GC or HPLC chromatogram, IR, NMR,
or mass spectra data.
If the data are not in your possession or not known to be
extant elsewhere, provide Ms. Liem with a written statement from
you or another responsible management official attesting to that
fact. According to FIFRA Books and Records regulations, 40 CFR
Section 169.2 (k) , all underlying raw data for the test reports
submitted to the Agency shall be retained by the producer for as
long as the registration is valid.
. Pursuant to regulations appearing at 40 CFR Part 2, Subpart B,
and specifically, Section 2.307,'you are entitled to claim any or
all of the information provided" to EPA as confidential business
information. If you do not assert a confidentiality claim, the
information may be made available to the public without further
notice. Such information can be disclosed by EPA only in
accordance with the procedures set forth in the regulations (cited
above). Any such claim for confidentiality must conform to the
requirements set forth in 40 CFR Section 2.203 (b).
Please provide the information directly to Ms. Liem by
December 17, 1987. If the data are not provided by this date, we
will consider it missing data according to the FIFRA Books and
Records regulations, 40 CFR Section 169.2 (k) . If you have
specific questions regarding this request Ms. Liem may be reached
at:
Environmental Protection Agency
Office of Compliance Monitoring (7204W)
401 M Street, SW
Washington, D.C. 20460
Phone: (703) 308-8333
Sincerely,
David L. Dull, Director
Laboratory Data Integrity
Assurance Division
cc: Ann Donargo (Sample Test Facility 000123)
2
-------
APPENDIX D
FIFRA COMPLIANCE CHECKLIST
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
GLP COMPLIANCE INSPECTION CHECKLIST
PART I - GENERAL
GLP FACILITY INSPECTION
Name: Date:
Address: Insp. No.
City: . State: Zip: .
Phone No.: „ Contact Person: : ,
FACILITY INFORMATION:
Is this facility:
a sponsor lab?
a contractor lab?
a management company?
What types of studies are conducted here {i.e., toxicology, chemical analysis, field)
PREINSPECTION REVIEW: (Obtained from Regional Office Files)
Oate(s) of Previous EPA Inspection(s):
Previous Findings:
REASON FOR INSPECTION; The purpose of this inspection is to determine if the facility is in compliance with trie
requirements of FIFRA, codified in 40 CFR Part 160. .
n Randomly Selected Neutral Inspection
H Selected for Cause
O Referral from _____ ,
O Other: (Specify) ; ;
£LCDA RFRA GLP INSPECTION CHFCKUST
General lnfcfrnj;
-------
Insp.
Laboratory: _ '. Init.: •• Date:
Comments (Please refer to subpart, section, or page numbers):
F1FRA GLP INSPECTION CHECXLJST
Data Audit R«v^ew
Revu«d 9/33
-------
Insp.
Laboratory: . . ; Init.: Date:
OPENING CONFERENCE
PRELIMINARY INFORMATION
1. Laboratory personnel present and interviewed:
' Title:
Name: _ . Title:
Title:
Title:
2. EPA inspector accompanied:
Name:
Name: —. Agency:
3. Credentials presented to:
4. "Notice of Inspection* signed by laboratory official and copy provided to official? Q Yes D No
5. Was a GLP Compliance Review conducted? . D Yes O No
If so, complete Form I. '
6. Was a data audit (or audits) conducted? D Yes G No
If so, complete Form II for each study audited.
List of studies audited:
CLOSING CONFERENCE (to be completed at conclusion of the inspection)
A. Date: Time: Where conducted:
Facility Representative(s) Present:
Name: , Title: —
Name: , Title: —
. Name: ; Title:
O CDA nFRA GLP INSPECTION CHECKLIST
General Information
Revised 9/93
-------
Insp.
Laboratory: - -. -
Comments (Please rarfar to subpart, section, or page numbers):
nFRA GL? INSPECT1°N CHECKLIST
' Dat3 Audit Review
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
CLOSING CONFERENCE (to be completed at conclusion of the inspection)
B. Were facility officials provided copies of:
Q Receipt for Samples and Documents n Inspection Confidentiality Notice
H Updated Regulations/Guidances n Declaration of Confidential Business Information
C. Were any documents, records, etc. requested from the facility? E yes D no
(If yes, include the list of information requested, and when it is due to be sent)
D. Does the inspector need to conduct any further follow-up activities? Q yes . D no
(If yes, please attach an explanation of what must be done, and a projected schedule for the completion of all
follow-up activities.)
Inspector's Signature: '. '• Date of Signature:
NOTES:
RFRA GLP INSPECTION CHECKLIST
General Information
Revised 9/93
-------
Insp.
Laboratory: -^ _—. Init.: . Date:
Bbrnments
[Pfeasa nrfar to subpart, section, or page numbers):
U GLP INSrE-mCN CHEC
Data Audh
9/"S3
-------
Laboratory:
Insp.
Init.:
Date:
PART II - GLP COMPLIANCE REVIEW CHECKLIST
FORM I —GLP COMPLIANCE .REVIEW
Were any ongoing studies available? "Please-complete this form for each-ongoing study selected.
Study selected for review: _" -
Test substance: -" ;
Study title: ; ;
Lab ID No.: '. \
Sponsor (name and address):
Study director:
Study initiation date:
Proposed completion date:
GENERAL INSTRUCTIONS/INFORMATION
1. For any *No* answers, provide explanation.
2. Remarks can be continued in the 'Comments* section on the back of each page.
3. Place a line through any item missing. For example, '...name/cignatura...'
SUBPART A
5160.10
SUBPART B
5160.29
— GENERAL PROVISIONS
Applicability to studies performed under grants and contract:
Has laboratory, contractor, or grantee been informed that
their services must be conducted in compliance with 40 CrR
Part 160?
- ORGANIZATION & PERSONNEL
Personnel
(a) Are training, education, and experience adequate?
(b) Are training and experience records available?
(c) Is th» number of personnel adequate?
(d) Are personnel health and sanitation precautions being
followed?
(el Is appropriate clothing available and worn as. needed?
(f) Are any personnel ill to the extent mat they have an
adverse effect on the study?
• If so, are they excluded from direct contact with test
systems and substances?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
RFHA GLP INSPECTION GUCx: :S"
Compliance ••ev.^w
Revise-: .' 'J3
-------
Insp.
Laboratory: ; _ Init.: •— Date:
Comments (PteaM rvfar to subpart section, or page numbers):
RFRA GLP INSPECTION CHECXLJST
Data Audit Ravxjw
9-33
-------
Laboratory: _
FORM 1 - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ART
§160.31
B - ORGANIZATION & PERSONNEL
Testing facility management
(a) Was a study director designated for ongoing study prior
to study initiation?
(b) Has the study director been replaced?
If so, was this done promptly?
(c) Is a quality assurance unit in place?
(d) Are personnel, resources, facilities, equipment,
materials, and methodologies available as scheduled?
(e) Do personnel clearly understand the functions they are
to perform?
(f) Have deviations in the study been communicated to the
study director, and have corrective actions been taken
and documented?
§160.33
Study director
Does the study director have adequate education, training,
and experience?
Is s/he familiar with all aspects of the study?
Does the study director understand that his/her
responsibilities include the following assurances:
(a) The protocol, including any change, is approved and
followed?
(b) All experimental data are accurately recorded and
verified?
(c) Unforeseen circumstances have been noted and
corrective actions taken and documented?
(d) Test systems are as specified in the protocol?
(e) All GLPs are followed?
(f) All data, as required, were transferred to the archives?
§160.35
Quality Assurance Unit
(a) Was a separate and independent QAU in place at the
time of the study?
(b) Did the QAU:
(1) Maintain a complete copy of the master schedule
indexed by test substance? (The required elements
include the test substance, test system, nature of
study, date initiated, current status, identity of
sponsor, name of study director.)
(2) Maintain copies of protocols?
YES
NO
-
N/A
REMARKS
-
S-EPA
RFRA GLP INSPECTION CHECKLIal
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: — _____ Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
FIFRA GLP INSPECTJON CHECKLIST
Data Audit Review
10 Rev.sed 9 93
-------
Laboratory:
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPARTB
S160.35(b)
- ORGANIZATION & PERSONNEL
(3) Perform periodic QA inspections and maintain proper
records of each inspection?
YES
NO
N/A
REMARKS
- What aspects of the ongoing study have been
inspected to this point? When?
(4) Periodically submit to management and study
director written status reports on each study, noting
any problems and corrective actions taken?
(5) Keep dates indicating when management and the
study director were notified of inspection findings?
(6) Determine that no deviations were made without
proper authorization and documentation?
(c) Are the responsibilities and procedures, records, and
indexing methods recorded in writing?
(d) Were these procedures available for review?
SUBPART C - FACILITIES
51 60.41 General
Is the facility's physical layout appropriate to the study?
Is there an appropriate degree of separation between/among
testing facilities to ensure an appropriate study environment?
S 1 60.43 Testing system care facilities
Do the test system care facilities have:
(a) Sufficient number of animal rooms for proper separation
of species and projects?
(1) Are plants or aquatic animals housed in separate
chambers or aquaria?
(2) Are aquatic toxicity tests isolated for individual
projects?
(b) Sufficient number of areas to ensure isolation of studies
involving biohazardous substances, including volatile
substances, aerosols, radioactive materials, and
infectious agents?
(c) Separate, isolated areas provided for the diagnosis,
treatment, and control of laboratory test system
diseases?
(d) Proper provisions for handling the collection and disposal
of contaminated water, soil, other spent materials, or
animal waste handled in order to minimize vermin
infestation, odors, disease hazards, and environmental
contamination?
(e) Provisions to regulate environmental conditions (e.g.,
temperature, humidity, photoperiod) as specified in the
protocol?
YES
NO
N/A
REMARKS
&EPA
.FIFRA GLP INSPECTION CHECKLIST
Compliance Review
Revised '3 33
-------
Insp.
Laboratory: '.—. . Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audu Review
12 Rev.seO 9'93
-------
Laboratory: —
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ART
§1 60.43
C - FACILITIES
(f) For marine organisms: is there an adequate supply of
clean seawater as specified in the protocol?
(g) For fresh water organisms: Is there an adequate supply
of clean water as specified in the protocol?
(h) For plants: Is there an adequate supply of soil as
specified in the protocol?
S 160.45
Test system supply facilities
Oo the test system supply facilities have:
(a) Storage areas for feed nutrients, soils, and bedding
separate from areas where the test systems are located
and protected against infestation and contamination?
- Appropriate means for preservation of perishable
supplies?
(b) The following plant facilities, as specified in the
protocol?
(1) Facilities for holding, culturing, and maintaining algae
and aquatic plants?
(2) Facilities for plant growth (e.g., greenhouses,
growth chambers, light banks, and fields)?
(c) Aquatic animal test facilities, including aquaria, holding
tanks, ponds, and ancillary equipment, as specified in
the protocol?
S 160.47
Facilities for handling test, control, and reference substances
Are separate areas for handling test, control, and reference
substances provided, including:
(a) To, prevent contamination or mixups:
(1) Separate areas for receipt and storage of
substances?
(2) Separate areas for mixing substances with a carrier?
(3) Separate storage areas for mixtures?
- Are these areas separate from those housing the
test systems?
§160.49
§160.51
Laboratory operation areas
Is separate laboratory space provided to perform routine and
specialized procedures as required by studies?
Specimen and data storage facilities
Is space provided for archives?
Is access to the archives limited?
YES
NO
N/A
REMARKS
13
F1FRA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9.93
-------
Insp.
Laboratory: . . Init.: . Date:
Comments (Please refer to subpart, section, or page numbers):
F1FRA GLP INSPECTION CHECKLIST
Data Audit Review
14 Revised 9/93
-------
Laboratory: ..
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
S 160.61
D - EQUIPMENT
Equipment design
Is equipment used in the generation of data and facility
environmental control of appropriate design and adequate
capacity to function according to protocol requirements?
Is the equipment in a suitable location for operation,
inspection, cleaning, and maintenance?
§160.63
Maintenance and calibration of equipment
(a) Was equipment adequately inspected, maintained, and
calibrated/standardized as required?
(b) Do the SOPs adequately address the methods, materials,
and schedules to be used in the routine inspection,
cleaning, maintenance, testing, and calibration/
standardization of equipment, including action taken in
case of a malfunction?
Is a specific contact person responsible for the .
performance of each operation?
(c) Are written records maintained of all inspection,
maintenance, testing, and/or calibrating/standardization
operations?
- Do these records describe whether the maintenance
operations were routine and followed the SOPs?
- Are written records kept of all non-routine repairs
performed as a result of failure or malfunction?
- Do the non-routine records document the nature of the
defect, how and when the defect was discovered, and
the remedial action taken in response?
- Are the records signed or initialled and dated by the
person making the entries?
SUBPART
§160.81
E - TESTING FACILITIES OPERATIONS
Standard Operating Procedures
(a) Are written SOPs available and adequate?
- Are deviations from the SOP adequately documented
in the raw data?
- Are significant changes properly authorized in writing
by management?
(b) Are written SOPs available for the following:
(1) -Test system area preparation?
(2) • Test system care?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
&EPA
15
RFRA GLP INSPECTION CHECKLlS I
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: ;— Init.: . Date:
Comments (Please refer to subpart, section, or page numbers):
F1FRA GLP INSPECTION DUCK US f
Data Audu Hev^w
16 RCV.^JO 3 33
-------
Laboratory:
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART E
S 160.81 (a)
- TESTING FACILITIES OPERATIONS
(3) Receipt, ID, storage, handling, mixing, and method
of sampling of the test, control, and reference
substances?
(4) Test system observations?
(5) Laboratory or other tests?
(6) Handling of test systems found moribund or dead?
(7) Necropsy of test systems or postmortem
. examination of test systems?
(8) Collection and ID of specimens?
(9) Histopathology?
(10) Data handling, storage, and retrieval?
(11) Maintenance and calibration of equipment?
(12) Transfer, proper placement, and ID of test systems?
(c) Are the latest revisions of relevant SOPs available to
each work area?
(d) Is a historical file of SOPs and dates of revisions
maintained?
5160.83
Reagents and solutions
Are all reagents and solutions labeled to indicate identity,
concentration, storage requirements, and expiration date?
- Are all materials within expiration date?
§ 160.90
Animal and other test system care
(a) Are SOPs available for housing, feeding, handling, and
care of test systems?
(b) Are newly received test systems isolated, and their
health status and appropriateness evaluated?
• Are these evaluations performed with acceptable
veterinary or scientific methods?
(c) At the initiation of the study, were test systems free of
disease for the study?
- If, during the study, a disease or condition developed,
ware test systems isolated?
- Were test systems treated for the condition in such a
manner that treatment did not interfere with the
study?
• Were the diagnosis, authorization of treatment,
description of treatment, and dates of treatment
documented in the raw data?
YES
l
NO
N/A
REMARKS
•
SEPA
17
RFRA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
. RFRA GLP INSPECTION CHECKLIST
Data Audit Review
13 Rev.-;.;,'j j ')3
-------
Laboratory: :
FORM I - GLP COMPUANCE REVIEW (Continued)
Insp.
Init.:
Date:
SU8PART E - TESTING FACILITIES OPERATIONS
S 160.90 (d) Were test systems needing to be removed from their
housing units adequately identified (e.g., tattoo, color
code, ear tag, ear punch, etc.)?
- Were test system housing units adequately identified?
(e) Were different species housed in separate rooms as
necessary?
• Were test systems of the same species used for
different studies housed in separate rooms?
- If the species were not housed in separate rooms, was
adequate differentiation by space and identification
made? •
(1) Were plants, invertebrate animals, and aquatic
vertebrate animals used in multispecies tests, if
housed in the same room, segregated to avoid mix-
up or cross contamination?
(f) Were cages, racks, pens, enclosures, aquaria, holding
tanks, ponds, growth chambers, and other holding,
rearing, and breeding areas, and accessory equipment
cleaned and sanitized at appropriate intervals?
(g) Were feed, soil, and water analyzed periodically for
contaminants?
• Was documentation maintained for. these analyses?
(h) Was the bedding used of a type that would not interfere
with the conduct of the study?
- Was the bedding changed as often as necessary?
(i) If any pest control materials were used, was their use
documented?
- Were pest control materials used that would not
interfere with the study?
(j) Were test systems acclimated to the environmental
conditions of the test?
YES
NO
N/A
REMARKS
--
...
SUBPART F - TEST. CONTROL AND REFERENCE SUBSTANCES
S160.105 Test control, and reference substance characterization
(a)
Have the substances been characterized?
- Identity
- Strength
• Purity
• Stability
- Uniformity
Test
Control
Reference
Documentation
v°/EPA
19
F1FRA GLP INSPECTION CHE CM
Compliance He^ew
Revised ') '33
-------
Insp.
Laboratory: —— Init.: Date:
Komments (Please refer to subpart, section, or page numbers):
SEPA
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
20 Revised 3/93
-------
Laboratory:
FORM I - GLP COMPUANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART F - TEST, CONTROL, AND REFERENCE SUBSTANCES
§160.105 - Were methods of synthesis, fabrication, or derivation
of the test, control, or reference substance
documented?
- Was the location of documentation specified?
(b) Were the solubility and/or stability of the substance .
determined before the experiment start date?
(c) Did each storage container for a test, control, or
reference substance include the following information:
• name, chemical abstracts service number (CAS) or
code number?
- batch number?
- expiration date, if any?
- storage conditions, if appropriate?
• Were storage containers assigned to a particular test
. substance for the duration of the study?
(d) For studies of more than 4 weeks experimental duration,
were reserve samples from each batch of test, control,
and reference substances retained for the period of time
provided in $160.195?
YES
NO
N/A
REMARKS
"
• Where are reserve samples archived?
(e) Was the stability of the substance under the storage
conditions at the test site known for all studies?
516O.107 Test, control, and reference substance handling
(a) Did an SOP covering handling of substances exist?
(b) Were the substances stored according to the SOP?
(c) Was distribution made so as to preclude the possibility
of contamination, deterioration, or damage?
(d) Was proper ID of substances maintained throughout the
distribution process?
(e) Was documentation maintained, including date and
quantity of each receipt and distribution?
5 160.1 13 Mixtures of substances with carriers
.(a) Was appropriate analytical testing performed for each
test, control, or reference substance:
(1) To determine uniformity?
• To determine, periodically, the concentration of
the test, control', or reference substance in the
mixture?
(2) To determine solubility in the mixture, if necessary?
- Was solubility testing done before the
experimental start date?
• '
&EPA
21
F1FRA GLP INSPECTION CHECKLIST
Compliance Rev.ew
Revised 3 93
-------
Insp.
Laboratory: Init.: Date:
Comments (Please refer to subpaix section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
22 Revised 9/93
-------
Laboratory:
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
5160.113
F - TEST, CONTROL. AND REFERENCE SUBSTANCES
(3) To determine the stability in the mixture before the
experimental start date or according to the SOP?
(b) Was the expiration date shown on the mixture container
if necessary?
(c) Was assurance made that the vehicle did not interfere
with the integrity of the test?
SUBPART
S 160.1 20
G - PROTOCOL FOR AND CONDUCT OF A STUDY
Protocol
(d) Does the study have an approved written protocol
indicating objectives and all methods?
• Does the protocol contain at least the following:
(1) A descriptive title and statement of purpose?
(2) Identification of the test, control, and reference
substance by name, CAS number, or code number?
(3) Name and address of both sponsor and testing
facility?
(4) Proposed experimental start and termination dates?
(5) Justification for selection of the test system?
(6) Where applicable, the number, body weight, range,
sex, source of supply, species, strain, substrain, and
age of the test system?
(7) Procedure for identification of the test system?
(8) Description of the experimental design, including
methods for the control of bias?
(9)~ A description and/or identification of the:
- diet used in the study?
- solvents, emulsifiers and/or other materials used
to solubilize or suspend the test, control, or
reference substance before mixing with the
carrier? .
- Specifications for acceptable levels of
contaminants?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
23
F1FRA GLP INSPECTION CHECKLIST
Compliance Review
Revised 3.93
-------
Insp.
Laboratory: '• — 'nit.: Date:
Comments (Pleas* refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Qata Audit Review
2-4 Revised 9/93
-------
Laboratory: i ;
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART G - PROTOCOL FOR AND CONDUCT OF A STUDY
S 160.120(a) (10) Route of administration and reason for its choice?
(11) Dosage level in appropriate units and method and
frequency of administration?
(12) Type and frequency of tests, analyses, and
measurements to be made?
(13) The records to be maintained?
(14) The date of approval of the protocol by the
sponsor?
- The dated signature of the study director?
(15) A statement of the proposed statistical method to
be used?
(e) Are all changes or revisions and reasons:
- documented?
- -signed by the study director?
- dated?
- maintained with the protocol?
S 160.1 30 Conduct of a study
(a) Was the study conducted in accordance with the
protocol?
(b) Were the test systems monitored in conformity with the
protocol?
(c) Are specimens identified by:
- test system?
- study?
• nature of collection?
• date of collection?
- Is the specimen information either on the container or
accompanying the specimen described in a manner
that precludes error?
(d) If applicable, are gross necropsy observations available
to the pathologist for the histopathological exam?
(e) Were all data recorded promptly and legibly in ink?
• Were all data entries (non-automated) signed (or
initialed) and dated on the day of entry?
YES
NO
N/A
..
REMARKS
25
RFRA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: — —. Init.: _ Date:
Comments (Please refer to subpart, section, or page numbers):
SEPA
RFRA GLP INSPECTION CHECKLIST
Data Audrt Review
26 . Revised 9/93
-------
Laboratory: :
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPARTG
J160.30(F)
- PROTOCOL FOR AND CONDUCT OF A STUDY
- Were changes in entries made so as not to obscure
the original entry?
- Were reasons given for changes?
- Were changes identified and dated?
- For automated data, was the individual responsible for
direct data input identified at the time of data input?
§160.135
Physical and chemical characterizations studies
. (a) Were all provisions of the GLP standards applied to
physical and chemical characterization studies designed
to determine stability, solubility, octanol water partition
coefficient, volatility, and persistence of test, control, or
reference substances?
S160.190
Storage and retrieval of records and data
(b) Do archives exist for orderly storage and expedient
retrieval of all raw data, documentation, protocols,
specimens, and interim and final reports?
• Are the conditions of the storage area appropriate to
minimize deterioration in accordance with the time
period of their retention and the nature of the
documents or specimens?
(c) Is an individual responsible for the archives?
(d) Is it specified that only authorized personnel have accesi
to the archives?
(e) Is the material retained in the archives indexed for rapid
retrieval?
YES
NO
N/A
REMARKS
27
RFRA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: . — Init.: — Date:
Comments (Please refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data Audit FUview
28
-------
Laboratory:
Insp.
Init.:
Date:
PART 111 - GLP DATA AUDfT REVIEW
FORM II - DATA AUGHT REVIEW
Please complete this form for each data audit selected.
Study selected for review:
Test substance: __
Study title:
Lab ID No.:
Sponsor (name and address):
Study director:
Study initiation date:
Study completion date:
Aspect of the study audited:
SUBPART
§160.10
5160.12
A - GENERAL PROVISIONS
Applicability to study performed under grant and contract
Was the laboratory, contractor, or grantee informed that
their services must be conducted in compliance with 40
CFR Part 1 60?
—
Compliance statement
(a) Was a compliance statement signed by the applicant?
the sponsor?
the study director?
(b) Was the compliance statement completed and
submitted with the study report? •
(c) Did the compliance statement include any statement of
differences from the GLP regulations?
YES
NO
N/A
REMARKS
"*
SEPA
29.
RFRA GLP INSPECTION CHI CM ib f
Data Audit Review
Rev-veO 'J S3
-------
Insp.
Laboratory: . ; : Init.: Date:
(Pleasa refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
30 Revised 9/93
-------
Laboratory: —.
FORM I! - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
§ 160.29
B - ORGANIZATION & PERSONNEL
Personnel
(a) Were training, education, and experience adequate?
(b) Were training and experience records available?
(c) Was the number of personnel adequate?
§160.31
Testing facility management
(a) Was a study director designated prior to study initiatign?
(b) Was the study director replaced during the course of the
study?
If so, was this done promptly?
(c) Was a quality assurance unit in place?
(d) Are personnel, resources, facilities, equipment, ;
materials, and methodologies available for inspection?
(e) Were deviations in the study communicated to the study
director and corrective actions taken and documented?
$160.33
Study director
Did the study director have adequate education, training, anc
experience?
Did the study director understand that his/her responsibilities
included the following assurances:
(a) The protocol, including any change, was approved and
followed?
(b) All experimental data were accurately recorded and
verified?
(c) Unforeseen circumstances were noted and corrective
action taken and documented?
(d) Test systems were as specified in the protocol?
(e) All GLPs were followed?
(f) All required data was transferred to the archives?
S 160.35
Quality Assurance Unit
(a) Was a separate and independent QAU in place at the
tim« of the study?
YES
NO
N/A
REMARKS
•
£EPA
31
RFRA GLP INSPECTION CHECKLIb.
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
Comments (PtoaM refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
32 Revised 9/93
-------
Laboratory:
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
init.:
Date:
SUBPAHT B
S 160.35
- ORGANIZATION & PERSONNEL
(b) Did the QAU:
(1 ) . Maintain a complete copy of the master schedule
indexed by test substance? (The required elements
include the test substance, test system, nature of
study, date initiated, current status, identity of
sponsor, name of study director.)
(2) Maintain copies of protocols?
(3) Perform periodic QA inspections and maintain proper
records of each inspection?
(4) Periodically submit to management and study
director written status reports on each study, noting
any problems and corrective actions taken?
(5) Keep dates indicating when management and the
study director were notified of inspection findings?
(6) Determine that no deviations were made without
proper authorization and documentation?
(c) Are the responsibilities and procedures, records, and
indexing methods recorded in writing?
(d) Were these procedures available for review?
SUSP ART C
§160.51
- FACILITIES
Specimen and data storage facilities
Is space provided for archives?
Is access to the archives limited?
SUBPAHT D
5 160.61
S 160.63
- EQUIPMENT
Equipment design
Was the equipment used in the generation of data and
facility environmental control appropriately designed and of
adequate capacity to function according to protocol
requirements?
Maintenance and calibration of equipment
(a) Was equipment adequately inspected, maintained, and
calibrated/standardized as required?
(b) Did the SOPs adequately address the methods,
materials, and schedules to be used in routine
inspection, cleaning, maintenance, testing, and
calibration/standardization of equipment, including actior
taken in case of a malfunction?
(c) Were written records maintained of all inspection,
maintenance, testing, and/or calibrating/standardization
operations?
YES
YES
YES
NO
NO
NO
N/A
N/A
N/A
REMARKS
—
•:-
REMARKS
-
REMARKS
33
RFRA GLP INSPECTION CHECKLIb.
Data Audit Review.
Revised 9.93
-------
Insp.
Laboratory: — _ Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHEOOJST
Data Audit R«v>«w
34 Rev\iad 9/33
-------
Laboratory: .
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART D - EQUIPMENT
1 1 60.63(c) • Did these records describe whether the maintenance
operations were routine and followed the SOPs?
- Were written records kept of all non-routine repairs
performed as a result of failure or malfunction?
• Did the non-routine records document the nature of
the defect, how and when the defect was discovered,
. and the remedial action taken in response?
- - Were the records signed or initialled and dated by the
person making the entries?
SUBPART E - TESTING FACILITIES OPERATIONS
$160.81 .Standard Operating Procedures
(a) Were written SOPs in place during the study adequate
and available for review?
- Are deviations from the SOP adequately documented
in the raw data?
- .Were all significant changes properly authorized in
writing by management?
(b) Were written SOPs available for the following:
(1 ) Test system area preparation?
(2) Test system care?
(3) Receipt, ID, storage, handling, mixing, and method
of sampling of the test, control, and reference
substances?
(4) Test system observations?
(5) Laboratory or other tests? ,
(6) Handling of test systems found moribund or dead?
(7) Necropsy of test systems or postmortem
examination of test systems?
(8) Collection and ID of specimens?
(9) Histopathology?
(10) Data handling, storage, and retrieval?
(11) Maintenance and calibration of equipment?
(12) Transfer, proper placement, and ID of test systems?
(c) Is a historical file of SOPs and dates of revisions
maintained?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
f:
• Y ' vw
SEPA
35
F1FRA GLP INSPECTION CHECKLIST
Data Audit Review
Rev.sed 9/93
-------
Insp.
Laboratory: , '. Init.: _ Date:
Comments (Pleas* refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audrt Review
36 Revised 9/93
-------
Laboratory:
FORM II - DATA ADOPT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART E - TESTING FACILITIES OPERATIONS
1 1 60.83 Reagents and solutions
Are records for reagents and solutions available that would
indicate identity, concentration, storage requirements, and
expiration date?
5 1 60.90 Animal and other test system care
(a) Were SOPs for housing, feeding, handling, and care of
test systems available?
(b) At the initiation of the study, were test systems free of
disease and appropriate for the study?
• If test systems developed a disease or condition during
the study, were test systems isolated?
• Were test systems treated for the condition in such a
manner that treatment did not interfere with the
study?
• Were the diagnosis, authorization of treatment,
description of treatment, and dates of treatment
documented in the raw data?
(c) Were test systems needing to be removed from their
housing units adequately identified (e.g., tattoo, color
code, ear tag, ear punch, etc.)?
- Were test system housing units adequately identified?
(d) Were different species housed in separate rooms as
necessary?
- Were test systems of the same species, used for
different studies, housed in separate rooms?
• If the species were not housed in separate rooms, was
adequate differentiation by space and identification
made?
(1) Were plants, invertebrate animals, and aquatic
vertebrate animals used in multispecies tests, if
housed in the same room, segregated to avoid mix-
up or cross contamination?
(e) Are records available indicating whether cages, racks,
pens, enclosures, aquaria, holding tanks, ponds, growth
chambers, and other holding, rearing, and breeding
areas, and accessory equipment were cleaned and
sanitized at appropriate intervals?
(f) Were feed, soil, and water analyzed periodically for
contaminants?
- Was documentation maintained for these analyses?
(g). Was the bedding used of a type that would not interfere
with the conduct of the study?
- Was the bedding changed as often as necessary?
YES
NO
N/A
REMARKS
'
37
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 3 03
-------
Insp.
Laboratory: — Init.: . Date:
Comments (Please refer to subpart, section, or page numbers):
FIFRA GLP INSPECTION CHECKLIST
Data Audit Review
38 Revised 9/93
-------
Laboratory: '.—
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
Init.:
.Date:
SUBPART E - TESTING FACULTIES OPERATIONS
5 160.90 (h) If any pest control materials were used, was their use
documented?
- Were pest control materials used that would not
interfere with the study?
(i) Were test systems acclimated to the environmental
conditions of the test?
YES
NO
N/A
REMARKS
SUBPART F - TEST, CONTROL AND REFERENCE SUBSTANCES
S160.105 Test, control, and reference substance characterization
(a) Were the substances characterized?
- Identity
- Strength
- Purity
- Stability
- Uniformity
SUBPART F - TEST, CONTROL. AND REFERENCE SUBSTANCES
Test
S 160. 105 (a) - Were methods of synthesis, fabrication, or derivation
of the test, control, or reference substance
documented and the location specified?
- Was the location of documentation specified?
(b) Were the solubility and/or stability of the test substance
determined before the experiment start date?
(c) Did each storage container for a test, control, or
reference substance include the following information:
- name, chemical abstracts service number (CAS) or
code number?
- batch number?
- expiration date, if any?
• storage conditions, if appropriate?
- Were storage containers assigned to a particular
substance for the duration of the study?
test
(d) For studies of more than 4 weeks experimental duration,
were reserve samples from each batch of test, control,
and reference substances retained for the period of time
provided in § 160. 195?
- Where are reserve samples archived?
(e) Was the stability of the substance under the storage •
conditions at the test site known for all studies?
Control
•
YES
NO
Reference Documentation
N/A
REMARKS
39
RFRA GLP INSPECTION CHECKLlbT
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: — : • 'nit.: Date:
Comments (Please refer to subpart, section, or page numbers):
F1FRAGLP INSPECTION CHECKLIST
Data Audit Kevnjw
40 Reviied 3 93
-------
Laboratory:
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ART F
§160.107
- TEST, CONTROL, AND REFERENCE SUBSTANCES
Test, control, and reference substance handling
(a) Did an SOP covering handling of substances exist?
(b) Were the substances stored according to the SOP?
(c) Was distribution made so as to preclude the possibility
of contamination, deterioration, or damage?
(d) Was proper 10 of substances maintained throughout the
distribution process?
(e) Was documentation maintained, including date and
quantity of each receipt and distribution?
§160.113
Mixtures of substances with carriers
(a) Was appropriate analytical testing performed for each
test, control, or reference substance:
(1) To determine uniformity?
- To determine, periodically, the concentration of
the test, control, or reference substance in the
mixture?
(2) To determine solubility in the mixture, if necessary?
- Was solubility testing done before the
experimental start date?
(3) To determine the stability in the mixture before the
experimental start date or according to the SOP?
(b) Was the expiration date shown on the mixture container,
if necessary?
(c) Was assurance made that the vehicle did not interfere
-with the integrity of the test?
SUBPARTG
S 160.1 20
- PROTOCOL FOR AND CONDUCT OF A STUDY
Protocol
(d) Did the study have an approved written protocol
indicating objectives and all methods?
- Did each protocol contain at least the following:
(1) A descriptive title and statement of purpose?
(2) Identification of the test, control, and reference
substance by name, CAS number, or code number?
(3) Name and address of both sponsor and testing
facility?
YES
YES
NO
NO
N/A
N/A
REMARKS
•
REMARKS
41
F1FRA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9.93
-------
Insp.
Laboratory: .—. —. . Init.: Date:
Comments (Pteasa refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
42 Revised 9/93
-------
Laboratory:
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ART
G - PROTOCOL FOR AND CONDUCT OF A STUDY
! 160.120(a) (4) Proposed experimental start and termination dates?
(5) • Justification for selection of the test system?
(6) Where applicable, the number, body weight, range,
sex, source of supply, species, strain, substrain, and
age of the test system?
(7) Procedure for identification of the test system?
(8) Description of the experimental design, including
methods for the control of bias?
(9) A description and/or identification of the:
• diet used in the study?
- solvents, emulsifiers and/or other materials used tc
solubilize or suspend the test, control, or reference
substance before mixing with the carrier?
• specifications for acceptable levels of
contaminants?
(10) Route of administration and reason for its choice?
(11) Dosage level in appropriate units and method and
frequency of administration?
(12) Type and frequency of tests, analyses, and
measurements to be made?
(13) The records to be maintained?
(14) The date of approval of the protocol by the
sponsor?
- The dated signature of the study director?
(15) A statement of the proposed statistical method to
be used?
(e) Were all changes or revisions and reasons:
• documented?
• signed by the study director?
- dated?
• maintained with the protocol?
5160.130
Conduct of a study
(a) Was the study conducted in accordance with the
protocol?
YES
NO
N/A
REMARKS
SEPA
43
F1FRA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
- RFRA GLP INSPECTION CHCOcnsr
Data Audit *ev.*,w
44 Rev.s.rO .' •)}
-------
Laboratory:
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ART G
5160.130
- PROTOCOL FOR AND CONDUCT OF A STUDY
(b) Were the test systems monitored in conformity with the
protocol?
(c) Were the specimens identified by:
- test system?
- study?
• nature of collection?
- date of collection?
- Was the specimen information either on the container
or accompanying the specimen described in a manner
that precludes error?
(d) If applicable, were the gross necropsy observations
available to the pathologist for the histopathological
exam?
(e) Were all data recorded promptly and legibly in ink?
- Were all data entries (non-automated) signed (or
initialed) and dated on the day of entry?
• - Were changes in entries made so as not to obscure the
original entry?
- Were reasons given for changes?
• Were changes identified and dated?
- For automated data, was the individual responsible for
direct data input identified at the time of data input?
§160.135
Physical and chemical characterizations studies .
(a) Were all provisions of the GLP standards applied to
physical and chemical characterization studies designed
to determine stability, solubility, octanol water partition
coefficient, volatility, and persistence of test, control, or
reference substances?
SUBPARTJ
5160.185
- RECORDS AND REPORTS
Reporting of study results
(a) Was- a final report prepared to contain at least the
following?
(1) .Name and address of the facility performing the
study?
- the dates on which the study was initiated,
completed, terminated, or discontinued?
YES
YES
NO
NO
N/A
•
N/A
REMARKS
REMARKS
SEPA
F1FRA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: __ — Init.: ; Date:
Comments (Please refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data Audit Review
46
-------
Laboratory: —.
FORM I! - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART J - RECORDS AND REPORTS
5l60.185(a| (2) The objectives and procedures as stated in the
approved protocol?
(3) The statistical methods employed?
(4) The test, control, and reference substance identified
by name, CAS number or code number, strength,
purity, and composition?
(5) Stability and, if needed, solubility, of the substances
under conditions of administration?
(6) A description of the methods used?
(7) A description of the test system used?
- Where applicable, the number of animals used,
sex, body weight range, source of supply, species,
strain and substrain, age, and procedures used for
ID?
(8) A description of the dosage, dosage regimen, route
of administration, and duration?
(9) A description of all of the circumstances that may
have affected the quality or integrity of the data?
(10) The name of the study director?
- The names of other scientists, professionals, and
supervisory personnel?
(11) A description of the transformations, calculations, or
operations performed on the data?
• A summary and analysis of the data?
- A statement of conclusions drawn from the data?
(12) Signed and dated reports of each of the individual
scientists or other professionals involved in the
study, including each person who conducted an
analysis or evaluation of data or specimens?
(13) The locations where all specimens, raw data, and
the final report are to be stored?
(14) A QAU statement prepared and signed as specified
in S160.35(b)(7}7
(b) Was the final report signed and dated by the study
director?
(c) Were corrections or additions to the final report in the
form of an amendment by the study director?
YES
NO
N/A
REMARKS
&EPA
47
F1FRA GLP INSPECTION Chi i m
Data Audit -v.
-------
Insp.
Laboratory: , ; __ Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
RFRA GLP INSPECTION CWCxi
Data Audit Hev>ew
48 Revised J 'J3
-------
Laboratory:
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART J - RECORDS AND REPORTS
§160.185{c) - Were the amendments clearly identified with:
• reasons for change?
- date?
- signature of person responsible?
(d) Is a copy of the final report with amendments
maintained by the sponsor and the test facility?
YES
NO
N/A
•
REMARKS
§ 160.19O Storage and retrieval of records and data
(a) Where are the raw data for the study archived in
compliance with this section?
(b) Were all raw data, documentation, records, protocols,
specimens, and final reports retained which were
generated as a result of a study?
- Were all correspondence and other documents relating
to interpretation and evaluation of data, other than
those contained in the final report, retained?
(c) Are archives provided for orderly storage and expedient
retrieval of all raw data, documentation, protocols,
specimens, and interim and final reports?
- Are the conditions of the storage area appropriate to
minimize deterioration in accordance with the time
period of their retention and the nature of the
documents or specimens?
(d) Is an individual responsible for the archives?
(e) Is it specified that only authorized personnel have access
to the archives?
(f) Is the material retained in the archives indexed for rapid
retrieval?
§160.195 Retention of records
(1) Does the sponsor hold a research or marketing
permit for the test substance?
If Yes, are the data retained?
(2) Has the sponsor applied for, but not received, a
research or marketing permit?
If Yes, were the data retained for at least five years?
(3) If the answer to (a) or (b) above is No, were the data
retained for at least two years?
(d) Are wet specimens, samples of test, control, or
reference substances, and specially prepared material
that are relatively fragile and differ markedly in stability
and quality during storage retained only as long as the
quality of the preparation affords evaluation?
SEPA
49
RFRA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: _ _. Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data AU(jit Review
50 Revised 9/93
-------
Laboratory:
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
I nit.:
Date:
SUBPART J
5160.195
- RECORDS AND REPORTS
(e) Were the master schedule sheet, copies of protocols,
and records of quality assurance inspections, as required
by 160.35|c), maintained by the QAU as an easily-
accessible system of records for the period of time
specified in questions 1 or 2 of this section?
(f) Were provisions in place to retain summaries of training,
experience, and job descriptions, required to be
maintained by 160.29(b), as well as all other testing
facility employment records for the length of time
specified in questions 1 or 2 of this section?
(g) Were provisions in place to retain records and reports of
the maintenance, calibration, and inspection of
equipment, as required by 160.63(b) and (c), for the
length of time specified in questions 1 or 2 of this
section?
(h) Were provisions in place to retain records required by
this part either as original records or as true copies such
as photocopies, microfilm, microfiche, or other accurate
reproductions of the original records?
§169.2(10
4O CFR 169 Books and Records
• Does the sponsor currently hold a research or
marketing permit for the test substance?
If Yes, were the original raw data for this study
retained?
YES
NO
N/A
REMARKS
If Yes, where are raw data retained?
SEPA
51
RFRA GLP INSPECTION CHECKuaT
Data Audit Review
Revised 0.33
-------
APPENDIX E
GLP TSCA COMPLIANCE CHECKLIST
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
GLP COMPLIANCE INSPECTION CHECKLIST
PART I - GENERAL
GLP FACILITY INSPECTION
Name: ; Date:
Address: ; Insp. No.
City: — State: Zip: .
Phone No.: ; Contact Person: '.
FACILITY INFORMATION: ..
Is this facility:
a sponsor lab?
a contractor lab?
a management company?
What types of studies are conducted here (i.e., toxicology, chemical analysis, field)
PRE1NSPECT1ON REVIEW: (Obtained from Regional Office Files)
Date(s) of Previous EPA Inspection(s):
Previous Findings:
REASON FOR INSPECTION: The purpose of this inspection is to determine if the facility is in compliance with the
requirements of TSCA, codified in 40 CFR Part 792.
D Randomly Selected Neutral Inspection
O Selected for Cause
O Referral from- _^ ', ;
D Other: (Specify)
TSCA GLP INSPECTION CHECKLIbi
General Information
Revised 3/93
-------
Insp.
Laboratory: ; ln't.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9/93
-------
Insp.
Laboratory: : lnit-: Date:
~~~"" OPENING CONFERENCE
PRELIMINARY INFORMATION
1. Laboratory personnel present and interviewed:
Namo- ,....,.,.
Nam«-
2. EPA inspector accompanied:
Nam«r
Nam*}; _
3. Credentials prftsuntad to:
T'r'p-
T;ti^.
Titlftr . ,
T;ri«.
Title-
Agonry _ . .
Agoncy: - -
4. 'Notice of Inspection* signed by laboratory official and copy provided to official? D Yes a No
5. Was a GLP Compliance Review conducted? O Yes CJ NO
If so, complete Form I.
6. Was a data audit (or audits) conducted? O Yes O NO
If so, complete Form II for each study audited.
List of studies audited:
CLOSING CONFERENCE (to be completed at conclusion of the inspection)
A. Date: . Time: — Where conducted:
Facility Representative(s) Present:
Name: • Title: —
Name: Title: —
Name: Title:
TSCA GLP INSPECTION
General lot
-------
Insp.
Laboratory: '. ; Init.: Date:
Comments (Pleasa refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECXLlST
Data Audrt R«v«ew
9'-9 3
-------
Insp.
Laboratory: . Init.: Date:
CLOSING CONFERENCE (to be completed at conclusion of the inspection)
B. Were facility officials provided copies of:
O Receipt for Samples and Documents D Inspection Confidentiality Notice
O Updated Regulations/Guidances n Declaration of Confidential Business Information
C. Were any documents, records, etc. requested from the facility? O yes O no
(If yes, include the list of information requested, and when it is due to be sent)
D. Does the inspector need to conduct any further follow-up activities? O yes O no
(If yes, please attach an explanation of what must be done, and a projected schedule for the completion of all
follow-up activities.)
Inspector's Signature: — Date of Signature;
NOTES:
« CDA TSCA GLP INSPECTION CHECKL.
General Information
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
Comment* (PlaaM refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9/93
-------
Laboratory:
Insp.
Init.:
Date:
PART II - GLP COMPLIANCE REVIEW CHECKLIST
FORM I - GLP COMPLIANCE REVIEW
Were any ongoing studies available? Please complete this form for each ongoing study selected.
Study selected for review:
Test substance:
Study title:
Lab ID No.: '.
Sponsor (name and address): ,
Study director:
Study initiation date:
Proposed completion date:
GENERAL INSTRUCTIONS/INFORMATION
1. For any "No* answers, provide explanation.
2. Remarks can be continued in the "Comments" section on the back of each page.
3. Place a line through any item missing. For example, "...name/cignaturo...*
SUBPART
§792.10
SUBPART
5792.29
A - GENERAL PROVISIONS
Applicability to studies performed under grants and contract]
Has laboratory, contractor, or grantee been informed that
their services must be conducted in compliance with 40 CFR
Part 792?
B - ORGANIZATION & PERSONNEL
Personnel
(a) Are training, education, and experience adequate?
(b) Are training and experience records available?
(c) Is the number of personnel adequate?
(d) Are personnel health and sanitation precautions being
followed?
(e) Is appropriate clothing available and worn as needed?
(f) Are any personnel ill to the extent that they have an
adverse effect on the study?
- If so, are they excluded from direct contact with test
systems and substances?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9 93
-------
Insp.
Laboratory: —. __ Init.: Date:
Comments (Ptoas* refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audrt Review
Revised 9/93
-------
Laboratory: _____
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPARTB
S792.31
- ORGANIZATION & PERSONNEL
Testing fadfity management
(a) Was a study director designated for ongoing study prior
to study initiation?
(b) Has the study director been replaced?
If so, was this done promptly?
(c) Is a quality assurance unit in place?
(d) Are personnel, resources, facilities, equipment,
materials, and methodologies available as scheduled?
(e) Do personnel clearly understand the functions they are
to perform?
(f ) Have deviations in the study been communicated to the
study director, and have corrective actions been taken
and documented?
5792.33
Study director
Does the study director have adequate education, training,
and experience?
Is s/he familiar with all aspects of the study?
Does the study director understand that his/her
responsibilities include the following assurances:
(a) The protocol, including any change, is approved and
followed?
(b) All experimental data are accurately recorded and
verified?
(c) Unforeseen circumstances have been noted and
corrective actions taken and documented?
(d) Test systems are as specified in the protocol?
(e) All GLPs are followed?
(f) All data, as required, were transferred to the archives?
S792.35
Quality Assuranca Unit
(a) Was a separate and independent QAU in place at the
time of the study?
(b) DidtheQAU:
(1) Maintain a complete copy of the master schedule
indexed by test substance? (The required elements
include the test substance, test system, nature of
study, date initiated, current status, identity of
sponsor, name of study director.)
(2) Maintain copies of protocols?
YES
NO
N/A
REMARKS
SEPA
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: ', ; . Init.: Date:
Comments (Pleas* refer to subpart, section, or page numbers):
• TSCA GLP 'NSPECTION CHECKLIST
03^ Audjt Rev,ew
10 Rev.scHJ Tn
-------
Laboratory: —— .
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUSP ARTS
5792.35(b|
- ORGANIZATION & PERSONNEL
(3) Perform periodic QA inspections and maintain proper
records of each inspection?
YES
NO
N/A
REMARKS
What aspects of the ongoing study have been
inspected to this point? When?
(4) Periodically submit to management and study
director written status reports on each study, noting
. any problems and corrective actions taken?
(5) Keep dates indicating when management and the
study director were notified of inspection findings?
(6) Determine that no deviations were made without
proper authorization and documentation?
(c) Are the responsibilities and procedures, records, and
indexing methods recorded in writing?
(d) Were these procedures available for review?
SUBPART
5792.41
S792.43
C - FACILITIES
General
Is the facility's physical layout appropriate to the study?
Is there an appropriate degree of separation between/among
testing facilities to ensure an appropriate study environment?
Testing system care facilities
Do the test system care facilities have:
(a) Sufficient number of animal rooms for proper separation
of species and projects?
(1) Are plants or aquatic animals housed in separate
chambers or aquaria?
(2) Are aquatic toxicity tests isolated for individual
projects?
(b) Sufficient number of areas to ensure isolation of studies
involving biohazardous substances, including volatile
substances, aerosols, radioactive materials, and
infectious agents?-
(c) Separate, isolated areas provided for the diagnosis,
treatment, and control of laboratory test system
diseases?
(d) Proper provisions for handling the collection and disposal
of contaminated water, soil, other spent materials, or
animal waste handled in order to minimize vermin
infestation, odors, disease hazards, and environmental
contamination?
(e) Provisions to regulate environmental conditions (e.g.,
temperature, humidity, photoperiod) as specified in the
protocol?
YES
NO
N/A
REMARKS
oEPA
11
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9 93
-------
Insp.
Laboratory: Init.: • Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHfCKl ISr
Data Audit Hev«ew
.12 Revised'•.) 33
-------
Laboratory: _ . —
FORM I - GLP COMPUANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
1792.43
C - FACJUTIES
(f) For marine oroarii^rny: is there an adequate supply of
clean seawater as specified in the protocol?
(g) For fresh water organisms: Is there an adequate supply
of clean water as specified in the protocol?
(h) For plants: Is there an adequate supply of soil as
specified in the protocol?
S792.45
Test system supply facilities
Do the test system supply facilities have:
(a) Storage areas for feed nutrients, soils, and bedding
separate from areas where the test systems are located
and protected against infestation and contamination?
• Appropriate means for preservation of perishable
supplies?
(b) The following plant facilities, as specified in the
protocol?
(1) Facilities for holding, culturing, and maintaining algat
and aquatic plants?
(2) Facilities for plant growth (e.g., greenhouses,
growth chambers, light banks, and fields)?
(c) Aquatic animal test facilities, including aquaria, holding
tanks, ponds, and ancillary equipment, as specified in
the protocol?
5792.47
Facilities for handling test, control, and reference substances
Are separate areas for handling test, control, and reference
substances provided, including:
(a) To prevent contamination or mixups:
(1 ) Separate areas for receipt and storage of
substances?
(2) Separate areas for mixing substances with a carrier?
(3) Separata storage areas for mixtures?
• Are these areas separate from those housing the
test systems?
S792.49
5792.51
Laboratory operation areas
Is separate laboratory space provided to perform routine and
specialized procedures as required by. studies?
Specimen and data storage facilities
Is space provided for archives?
Is access to the archives limited?
YES
NO
N/A
REMARKS
&EPA
13
TSCA GLP INSPECTION CHECKLIST
Compliance Revew
1 'J3
-------
Insp.
Laboratory: ; Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
14 Revised 9:93
-------
Laboratory: — — — '
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
5792.61
D — EQUIPMENT
Equipment design
Is equipment used in the generation of data and facility
environmental control of appropriate design and adequate
capacity to function according to protocol requirements?
Is the equipment in a suitable location for operation,
inspection, cleaning, and maintenance?
§792.63
Maintenance and calibration of equipment
(a) Was equipment adequately inspected, maintained, and
calibrated/standardized as required?
(b) Do the SOPs adequately address the methods, materials,
and schedules to be used in the routine inspection,
cleaning, maintenance, testing, and calibration/
standardization of equipment, including action taken in
case of a malfunction?
Is a specific contact person responsible for the
performance of each operation?
(c) Are written records maintained of all inspection,
maintenance, testing, and/or calibrating/standardization
operations?
- Do these records describe whether the maintenance
operations were routine and followed the SOPs?
- Are written records kept of all non-routine repairs
performed as a result of failure or malfunction?
- Do the non-routine records document the nature of the
defect, how and when the defect was discovered, and
the remedial action taken in response?
- Are the records signed or initialled and dated by the
person making the entries?
SUBPAHT
5 792.81
E - TESTING FACILITIES OPERATIONS
Standard Operating Procedures
(a) Are written SOPs available and adequate?
- Are deviations from the SOP adequately documented
in the raw data?
• Are significant changes properly authorized in writing
by management?
(b) Are written SOPs available for the following:
(1) Test system area preparation?
(2) Test system care?
YES
YES
NO
NO
•
N/A
N/A
REMARKS
-
REMARKS
6EPA
15
TSCA GLP INSPECTION CHf CKI is T
Compliance «<
-------
Insp.
Laboratory: _ Init.: Date:
Comments (Pteasa refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data Audit Review
' 15 Revised 9.-93
-------
Laboratory: - —
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART E
S 792.81 (a)
- TESTING FACILITIES OPERATIONS
(3) Receipt, ID, storage, handling, mixing, and method
of sampling of the test, control, and reference
substances?
(4) Test system observations?
(5) Laboratory or other tests?
(6) Handling of test systems found moribund or dead?
(7) Necropsy of test systems or postmortem
examination of test systems?
(8) Collection and 10 of specimens?
(9) Histopathology?
(10) Data handling, storage, and retrieval?
(11) Maintenance and calibration of equipment?
(12) Transfer, proper placement, and ID of test systems?
(c) Are the latest revisions of relevant SOPs available to
each work area?
(d) Is a historical file of SOPs and dates of revisions
maintained?
§792.83
Reagents and solutions
Are all reagents and solutions labeled to indicate identity,
concentration, storage requirements, and expiration date?
- Are all materials within expiration date?
§792.90
Animal and other test system care
(a) Are SOPs available for housing, feeding, handling, and
care of test systems?
(b) Are newly received test systems isolated, and their
health status and appropriateness evaluated?
• Are these evaluations performed with acceptable
veterinary or scientific methods?
(c) At the initiation of the study, were test systems free of
disease for the study?
- If, during the study, a disease or condition developed,
were test systems isolated?
• Were test systems treated for the condition in such a
manner that treatment did not interfere with the
study?
• Were the diagnosis, authorization of treatment,
description of treatment, and dates of treatment
documented in the raw data?
YES
NO
N/A
REMARKS
•
SEPA
17
TSCA GLP INSPECTION CHECKLIS.
Compliance Review
.Revised 9/93
-------
Insp.
Laboratory: ' '. Init.: Date:
Comments (Pleas* refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data Audit Review
18 Revised 9.93
-------
Laboratory: —
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART E - TESTWG FAOLTTIES OPERATIONS
1792.90 (d) Were test systems needing to be removed from their
housing units adequately identified (e.g., tattoo, color
code, ear tag, ear punch, etc.)?
- Were test system housing units adequately identified?
(e) Were different species housed in separate rooms as
necessary?
• Were test systems of the same species used for
different studies housed in separate rooms?
• If the species were not housed in separate rooms, was
adequate differentiation by space and. identification
made?
(1) Were plants, in vertebrate animals, and aquatic
vertebrate animals used in muttispecies tests, if
• housed in the same room, segregated to avoid mix-
up or cross contamination?
(f) Were cages, racks, pens, enclosures, aquaria, holding
tanks, ponds, growth chambers, and other holding,
rearing, and breeding areas, and accessory equipment
cleaned and sanitized at appropriate intervals?
(g) Were feed, soil, and water analyzed periodically for
contaminants?
• Was documentation maintained for these analyses?
(h) Was the bedding used of a type that would not interfere
with the conduct of the study?
• Was the bedding changed as often as necessary?
(i) If, any pest control materials were used, was their use
documented?
- Were pest control materials used that would not
interfere with the study?
(j) Were test systems acclimated to the environmental
conditions of the test?
YES
NO
N/A
•
REMARKS
._
.
SUBPART F - TEST. CONTROL. AND REFERENCE SUBSTANCES
§792.105 Test, control, and reference substance characterization
(a)
Haw the substances been characterized?
- Identity
- Strength
- Purity
- Stability
- Uniformity
Test
•
Control
Refer tinea
Documentation
19
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9 33
-------
Insp.
Laboratory: .—— ,—. - Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCAGLP INSPECTION CHECKLIST
' Data Audit Review
20 Revved 3 33
-------
Laboratory: • • —
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART F - TEST, CONTROL. AND REFERENCE SUBSTANCES
§792.105 • Were methods of synthesis, fabrication, or derivation
of the test, control, or reference substance
documented?
• Was the location of documentation specified?
(b) Were the solubility and/or stability of the substance
determined before the experiment start date?
(c) Did each storage container for a test, control, or
reference substance include the following information:
- name, chemical abstracts service number (CAS) or
code number?
• batch number?
• expiration date, if any?
•
- storage conditions, if appropriate?
- Were storage containers assigned to a particular test
substance for the duration of the study?
(d) For studies of more than 4 weeks experimental duration,
were reserve samples from each batch of test, control,
and reference substances retained for. the period of time
provided in §792.195?
YES
NO
N/A
REMARKS
- Where are reserve samples archived?
(e) Was the stability of the substance under the storage
conditions at the test site known for all studies?
§792.107 Test, control, and reference substance handling
(a) Did an SOP covering handling of substances exist?
(b) Were the substances stored according to the SOP?
(c) Was distribution made so as to preclude the possibility
of contamination, deterioration, or damage?
(d) Was proper ID of substances maintained throughout the
distribution process?
(el Was documentation maintained, including date and
quantity of each receipt and distribution?
§792.1 13 Mixtures of substances with carriers
(a) Was appropriate analytical testing performed for each
test; control, or reference substance:
(1) To determine uniformity?
• To determine, periodically, the concentration of
the test, control, or reference substance in the
mixture?
(2) To determine solubility in the mixture, if necessary?
- Was solubility testing done before the
experimental start date?
oEPA
21
TSCA GLP INSPECTION CHECKUo ,
Compliance Review
Revised 9/93
-------
Insp.
Laboratory: Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCAGLP INSPECTION CHE CM i.sr
Data Au
-------
Laboratory:
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
§792.113
F - TEST, CONTROL. AND REFERENCE SUBSTANCES
(3) To determine the stability in the mixture before the
experimental start date or according to the SOP?
(b) Was the expiration date shown on the mixture container
if necessary?
(c) Was assurance made that the vehicle did not interfere
with the integrity of the test?
SUBPART
§792.120
G - PROTOCOL FOR AND CONDUCT OF A STUDY
Protocol
. (d) Does the study have an approved written protocol
indicating objectives and all methods?
- Does the protocol contain at least the following:
(1) A descriptive title and statement of purpose?
(2) Identification of the test, control, and reference
substance by name, CAS number, or code number?
(3) Name and address of both sponsor and testing
facility?
(4) Proposed experimental start and termination dates?
(5) Justification for selection of the test system?
(6) Where applicable, the number, body weight, range,
sex, source of supply, species, strain, substrain, and
age of the test system?
(7) Procedure for identification of the test system?
(8) Description of the experimental design, including
methods for the control of bias?
(9) A description and/or identification of the:
• diet used in the study?
- solvents, emulsifiers and/or other materials used
to solubilize or suspend the test, control, or
reference substance before mixing with the
carrier?
- Specifications for acceptable levels of
contaminants?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
•
SEPA
23
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised J '33
-------
Insp.
Laboratory: _ _____ Init.: . Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP 'NSPECTION CHECKLIST
Data Auc(it Review
.24 Revised 9-93
-------
Laboratory: . •
FORM I - GLP COMPLIANCE REVIEW (Continued)
Insp.
I nit.:
Date:
SUBPART G
5792.120(3)
- PROTOCOL FOR AND CONDUCT OF A STUDY
(10) Route of administration and reason for its choice?
(11) Dosage level in appropriate units and method and
frequency of administration?
(12) Type and frequency of tests, analyses, and
measurements to be made?
(13) The records to be maintained?
(14) The date of approval of the protocol by the
sponsor?
- The dated signature of the study director?
(15) A statement of the proposed statistical method to
be used?
(e) Are all changes or revisions and reasons:
- documented?
• signed by the study director?
- dated?
• maintained with the protocol?
5792.130
Conduct of a study
(a) Was the study conducted in accordance with the
protocol?
(b) Were the test systems monitored in conformity with the
protocol?
(c) Are specimens identified by:
- test system?
• study?
- nature of collection?
• date of collection?
• Is the specimen information either on the container or
accompanying the specimen described in a manner
that precludes error?
(d) If applicable, are gross necropsy observations available
to the pathologist for the histopathological exam?
(e) Were all data recorded promptly and legibly in ink?
- Were all data entries (non-automated) signed (or
initialed) and dated on the day of entry?
YES
.
NO
N/A
REMARKS
&EPA
25
TSCA GLP INSPECTION CHECKr.jF
Compliance Review
Revis«o ') '13
-------
Insp.
Laboratory: ; ; _. Init.: — Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
25 Revised 9.93
-------
Laboratory:
FORM I - GLP COMPUANCE REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART G
§792.30(F)
- PROTOCOL FOR AND CONDUCT OF A STUDY
- Were changes in entries made so as not to obscure
the original entry?
• Were reasons given for changes?
- Were changes identified and dated?
- For automated data, was the individual responsible for
direct data input identified at the time of data input?
S792.135
Physical and chemical characterizations studies
(a) Were all provisions of the GLP standards applied to
physical and chemical characterization studies designed
to determine stability, solubility, octanol -water partition
coefficient, volatility, and persistence of test, control, or
reference substances?
S792.190
Storage and retrieval of records and data
(b) Do archives exist for orderly storage and expedient
retrieval of all raw data, documentation, protocols,
specimens, and interim and final reports?
- Are the conditions of the storage area appropriate to
minimize deterioration in accordance with the time
period of their retention and the nature of the
documents or specimens?
(c) Is an individual responsible for the archives?
(d) Is it specified that only authorized personnel have access
to the archives?
(e) Is the material retained in the archives indexed for rapid
retrieval?
YES
NO
N/A
REMARKS
27
TSCA GLP INSPECTION CHECKLIST
Compliance Review
Revised 9.93
-------
Insp.
Laboratory: __ . Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
28 Revised 9/93
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Laboratory:
Insp.
Init.:
Date:
PART III - GLP DATA AUDIT REVIEW
FORM II - DATA AUDfT REVIEW
Please complete this form for each data audit selected.
Study selected for review:
Test substance:
Study title:
Lab ID No.:
Sponsor (name and address):
Study director:
Study initiation date:
Study completion date:
Aspect of the study audited:
SUSP ART
5792.10
5792.12
A - GENERAL PROVISIONS
Applicability to study performed under grant and contract
Was the laboratory, contractor, or grantee informed that
their services must be conducted in compliance with 40
CFR Part 792?
«» .-
Compliance statement
(a) Was a compliance statement signed by the applicant?
the sponsor?
the study director?
(b) Was the compliance statement completed and
submitted with the study report?
(c) Did the compliance statement include any statement of
differences from the GLP regulations?
YES
NO
N/A
REMARKS
SEPA
29
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9.33
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tnsp.
Laboratory: . : Init.: Date:
.(Please refer to subpart. section, or page numbers):
TSCA GL° INSPECTION CHECKLIST
Data Audit ?.ev.«jw
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Laboratory: :
FORM II - DATA AUDCT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
§792.29
B - ORGANIZATION & PERSONNEL
Personnel
(a) Were training, education, and experience adequate?
(b) Were training and experience records available?
(c) Was the number of personnel adequate?
5792.31
Testing facility management
(a) Was a study director designated prior to study initiation?
(b) Was the study director replaced during the course of the
study? . -
If so, was this done promptly?
(c) Was a quality assurance unit in place?
(d) Are personnel, resources, facilities, equipment,
materials, and methodologies available for inspection?
(el Were deviations in the study communicated to the study
director and corrective actions taken and documented?
$792.33
Study director
Did the study director have adequate education, training, anc
experience?
Did the study director, understand that his/her responsibilities
included the following assurances:
(a) The protocol, including any change, was approved and
followed?
(b) All experimental data were accurately recorded and
verified?
(c) Unforeseen circumstances were noted and corrective
action taken and documented?
(d) Test systems were as soe-ified in the protocol? .
(e) All GLPs were followed?
YES
NO
N/A
REMARKS
(f) All required data was transferred to the archives?
I I \ I
$792.35
Quality Assuranca Unit
(a) Was a separate and independent CAU in place at the
tima of the study?
TSCA GLP INSPECTION C-ECxi
Dsta Audit 'Jev
-------
Insp.
Laboratory: - : • ln't-:
Comments IPteasa refer to sufapart, section, or page numbers):
TSCA GL? INSrSCTlCN CH£CX::Sr
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Laboratory:
FORM II — DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART
S792.35
B - ORGANIZATION & PERSONNEL
(b) Did the OAU:
(1) Maintain a complete copy of the master schedule
indexed by test substance? (The required elements
include the test substance, test system, nature of
study, date initiated, current status, identity of
sponsor, name of study director.)
(2) Maintain copies- of protocols?
(3) Perform periodic QA inspections and maintain proper
records of each inspection?
(4) Periodically submit to management and study
director written status reports on each study, noting
any problems and corrective actions taken?
(5) Keep dates indicating when management and the
study director were notified of inspection findings?
(6) Determine that no deviations were made without
proper authorization and documentation?
(c) Are the responsibilities and procedures, records, and
indexing methods recorded in writing?
(d) Were these procedures available for review?
SUBPART
§792.51
C - FACILITIES
Specimen and data storage facilities
Is space provided for archives?
Is access to the archives limited?
SUBPART
§792.61
§792.63
D - EQUIPMENT
Equipment design
Was the equipment used in the generation of data and
facility environmental control appropriately designed and of
adequate capacity to function according to protocol
requirements?
Maintenanca and calibration of equipment
(a) Was. equipment adequately inspected, maintained, and
calibrated/standardized as required?
(bJ- Did the SOPs adequately address the methods,
materials, and schedules to be used in routine
inspection, cleaning, maintenance, testing, and
calibration/standardization of equipment, including actior
taken in case oi a malfunction?
(c) Were writtan records maintained of ail inspection,
. maintenance, testing, and/or calibrating/stancarcization
ooerations?
YES
YES
Y=S
NO
NO
NO
N/A
-'
N/A
N/A
REMARKS
REMARKS
REMARKS
TSCA GLP INSPECTION CHECKLIST
Data Audit ?.ev>ew
Revised 9 33
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Insp.
Laboratory: - Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
SERA - TSCA GLP INSPECTION CHECKLIST
^tiyi Data Audit Review
34 Revised 9/93
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Laboratory:
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART D
5792. 63(C)
- EQUIPMENT
- Did these records describe whether the maintenance
operations were routine and followed the SOPs?
• Were written records kept of all non-routine repairs
performed as a result of failure or malfunction?
- Did the non-routine records document the nature of
the defect, how and when the defect was discovered,
and the remedial action taken in response?
- Were the records signed or initialled and dated by the
person making the entries?
SUBPART E
S792.81
- TESTING FACILITIES OPERATIONS
Standard Operating Procedures
(a) Were written SOPs in place during the study adequate
and available for review?
- Are deviations from the SOP adequately documented
in the raw data?
- Were all significant changes properly authorized in
writing by management?
(b) Were written SOPs available for the following:
(1) Test system area preparation?
(2) Test system care?
(3) Receipt, ID, storage, handling, mixing, and method
of sampling of the test, control, and reference
substances?
(4) Test system observations?
(5) Laboratory or other tests?
(6) Handling of test systems found moribund or dead?
(7) Necropsy of test systems or postmortem
examination of test systems?
(8) Collection and ID of specimens?
(9) Histopathology?
(10) Data handling, storage, and retrieval?
(11) Maintenance and calibration of equipment?
(12) Transfer, proper placement, and ID of test systems?
(c) Is a historical fHe of SOPs and dates of revisions
maintained?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
oEPA
TSCA GLP INSPECTION Ci«( CK
Data Auo>t We
35
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Insp.
Laboratory: : lnit-: Datfl:
Comments (Ptoas« refer to subpart, section, or page numbers):
ERA TSCA GLP INSPECTION CHECKLIST
CJyT^ Data Audit Review
35 Revised 9/33
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Laboratory: —• —
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART E - TESTING FACILITIES OPERATIONS
i 792.83 Reagents and solutions
Are records for reagents and solutions available that would
indicate identity, concentration, storage requirements, and
expiration date?
§792.90 Animal and other test system care
(a) Were SOPs for housing, feeding, handling, and care of
test systems available?
(b) At the initiation of the study, were test systems free of
disease and appropriate for the study?
- If test systems developed a disease or condition during
the study, were test systems isolated?
- Were test systems treated for the condition in such a
manner that treatment did not interfere with the
study?
- Were the diagnosis, authorization of treatment,
description of treatment, and dates of treatment
documented in the raw data?
(c) Were test systems needing to be removed from their
housing units adequately identified (e.g., tattoo, color
code, ear tag, ear punch, etc.)?
• Were test system housing units adequately identified?
(d) Were different species housed in separate rooms as
necessary?
- Were test systems of the same species, used for
different studies, housed in separate rooms?
- If the species were not housed in separate rooms, was
adequate differentiation by space and identification
made?
(1) Were plants, invertebrate animals, and aquatic
vertebrate animals used in multispecies tests, if
housed in the same room, segregated to avoid mix-
up or cross contamination?
(e) Are records available indicating whether cages, racks,
pens, enclosures, aquaria, holding tanks, ponds, growth
chambers, and other holding, rearing, and breeding
areas, and accessory equipment were cleaned and
sanitized at appropriate intervals?
(f) Were feed, soil, and water analyzed periodically for
contaminants?
- Was documentation maintained for these analyses?
(g) Was the bedding used of a type that would not interfere
with the conduct of the study?
• Was the bedding changed as often as necessary?
YES
NO
N/A
REMARKS
•
.
SEPA
37
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9-93
-------
Insp.
Laboratory: — Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
SERA
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
38 Revised 9/93
-------
Laboratory: •
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
I nit.:
.Date:
SUBPART E - TESTING FACILITIES OPERATIONS
$792.90 (h) If any pest control materials were used, was their use
documented?
• Were pest control materials used that would not
interfere with the study?
(i) Were test systems acclimated to the environmental
conditions of the test?
YES
NO
N/A
REMARKS
SUBPART F - TEST, CONTROL, AND REFERENCE SUBSTANCES
S792.105 Test, control, and reference substance characterization
(a) Were the substances characterized?
- Identity
- Strength
- Purity
• Stability
- Uniformity
SUBPART F - TEST, CONTROL. AND REFERENCE SUBSTANCES
Test
5792.105(a) - Were methods of synthesis, fabrication, or derivation
of the test, control, or reference substance
documented and the location specified?
- Was the location of documentation specified?
(b) Were the solubility and/or stability of the test substance
determined before the experiment start date?
(c) Did each storage container for a test, control, or
reference substance include the following information:
-. name, chemical abstracts service number (CAS) or
code number?
- batch number?
- expiration date, if any?
• storage conditions, if appropriate?
• Were storage containers assigned to a particular
substance for the duration of the study?
test
(d) For studies of more than 4 weeks experimental duration,
were reserve samples from each batch of test, control,
and reference substances retained for the period of time
provided in 5792.195?
• Where are reserve samples archived?
(e) Was the stability of the substance under the storage
conditions at the test site known for all studies?
Control
YES
NO
Reference Documentation
N/A
REMARKS
39
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9.93
-------
Insp.
Laboratory: ; 'nit-: Date:
_ Comments (Please refer to subpart, section, or page numbers):
.TSCA GLP INSPECTION CHECKLIST
Data Audit Review
40 Revised 9.93
-------
Laboratory: ;
FORM II - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART F
S792.107
- TEST, CONTROL. AND REFERENCE SUBSTANCES
Test, control, and reference substance handling
(a) Did an SOP covering handling of substances exist?
(b) Were the substances stored according to the SOP?
(c) Was distribution made so as to preclude the possibility
of contamination, deterioration, or damage?
(d) Was proper ID of substances maintained throughout the
distribution process?
(e) Was documentation maintained, including date and
quantity of each receipt and distribution?
S792.113
Mixtures of substances with carriers
(a) Was appropriate analytical testing performed for each
test, control, or reference substance:
(1) To determine uniformity?
- To determine, periodically, the concentration of
the test, control, or reference substance in the
" mixture?
(2) To determine solubility in the mixture, if necessary?
- Was solubility testing done before the
experimental start date?
(3) To determine the stability in the mixture before the
experimental start date or according to the SOP?
--- (b) Was the expiration date shown on the mixture container,
if necessary?
~' .(c) Was assurance made that the vehicle did not interfere
.-.;•* with the integrity of the test?
:SUBPART G
§792.120
- PROTOCOL FOR AND CONDUCT OF A STUDY
Protocol
Id) Did the study have an approved written protocol
indicating objectives and all methods?
- Did each protocol contain at least the following:
(1) A descriptive title and statement of purpose?
(2) Identification of the test, control, and reference
substance by name, CAS number, or code number?
(3) Name and address of both sponsor and testing
-facility?
YES
YES
NO
NO
N/A
N/A
REMARKS
-
—
...
REMARKS
41
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9.93
-------
Insp.
Laboratory: . Init.: Date:
Comments (Pleas* refer to subpart, section, or page numbers):
GLP INSPECTION CHECKLIST
Data Audrt Review
.42 Revised 9 S3
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Laboratory: __—.
FORM II - DATA AUDrT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART G - PROTOCOL FOR AND CONDUCT OF A STUDY
§792.120(a) (4) Proposed experimental start and termination dates?
(5) Justification for selection of the test system?
(6) Where applicable, the number, body weight, range,
sex, source of supply, species, strain, substrain, and
age of the test system?
(7) Procedure for identification of the test system?
(8) Description of the experimental design, including
methods for the control of bias?
(9) A description and/or identification of the:
- diet used in the study?
- solvents, emulsifiers and/or other materials used tc
solubilize or suspend the test, control, or reference
substance before mixing with the carrier?
• specifications for acceptable levels of
contaminants?
(10) Route of administration and reason for its choice?
(11) Dosage level in appropriate units and method and
frequency of administration?
(12) Type and frequency of tests, analyses, and
measurements to be made?
(13) The records to be maintained?
(14) The date of approval of the protocol by the
sponsor?
- The dated signature of the study director?
(15) A statement of the proposed statistical method to
be used?
(e) Were all changes or revisions and reasons:
• documented?
- signed by the study director?
- dated?
• maintained with the protocol?
5792.130 Conduct of a study
(a) Was the study conducted in accordance with the
protocol?
YES
NO
N/A
REMARKS
43
-TSCA GLP INSPECTION CHECKLIST
Data Audit Rev.ew
Revised 3 33
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Insp.
Laboratory: — Init.: Date:
Comments (Please refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
44 Revised 9/93
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Laboratory: —
FORM II - DATA AUDFT REVIEW {Continued)
Insp.
Init.:
Date:
SUSP ART G
5792.130
- PROTOCOL FOR AND CONDUCT OF A STUDY
(b) Were the test systems monitored in conformity with the
protocol?
(c) Were the specimens identified by:
- test system?
- study?
- nature of collection?
- date of collection?
• Was the specimen information either on the container
or accompanying the specimen described in a manner
that precludes error?
(d) If applicable, were the gross necropsy observations
available to the pathologist for the histopathological
exam?
(e) Were all data recorded promptly and legibly in ink?
- Were all data entries (non-automated) signed (or
initialed) and dated on the day of entry?
• Were changes in entries made so as not to obscure the
original entry?
• Were reasons given for changes?
- Were changes identified and dated?
• For automated data, was the individual responsible for
direct data input identified at the time of data input?
§792.135
Physical and chemical characterizations studies
(a) Were all provisions of the GLP standards applied to
physical and chemical characterization studies designed
to determine stability, solubility, octanol water partition
coefficient, volatility, and persistence of test, control, or
reference substances?
SUBPART J
§792.185
- RECORDS AND REPORTS
Recocting of study results
(a) Was a final report prepared to contain at least the
following?
(1) Name and address of the facility performing the
study?
• the dates on which the study was initiated,
completed, terminated, or discontinued?
YES
YES
NO
NO
N/A
N/A
REMARKS
REMARKS
SEPA
TSCA GLP INSPECTION CHCCKliSf
Data Audit Hev*;«*
Revised ) 'H
-------
Insp.
Laboratory: — Init.: Date:
Comments (Pleas* refer to subpart, section, or page numbers):
&CDA TSCA GLP INSPECTION CHECKLIST
*^tl/n Data Audit Review
46 Revised 9/93
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Laboratory:
FORM II - DATA AUDIT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART J - RECORDS AND REPORTS
§792.185(a) (2) The objectives and procedures as stated in the
approved protocol?
(3) The statistical methods employed?
(4) The test, control, and reference substance identified
by name, CAS number or code number, strength,
purity, and composition?
(5) Stability and, if needed, solubility, of the substances
under conditions of administration?
(6) A description of the methods used?
(7) A description of the test system used?
- Where applicable, the number of animals or other
test systems used, sex, body weight range, source
of supply, species, strain and substrain, age, and
procedures used for ID?
(8) A description of the dosage, dosage regimen, route
of administration, and duration?
(9) A description of all of the circumstances that may
have affected the quality or integrity of the data?
(10) The name of the study director?
- The names of other scientists, professionals, and
supervisory personnel?
(11) A description of the transformations, calculations, or
operations performed on the data?
- A summary and analysis of the data?
- A statement of conclusions drawn from the data?
(12) Signed and dated reports of each of the individual
scientists or other professionals involved in the
study, including each person who conducted an
analysis or evaluation of data or specimens?
(13) The locations where all specimens, raw data, and
the final report are to be stored?
(14) A QAU statement prepared and signed as specified
in 5792.35(b)(7)?
(b) Was the final report signed and dated by the study
director?
(c) Were corrections or additions to the final report in the
form of an amendment by the study director?
YES
.
NO
N/A
REMARKS
•
SEPA
47
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9-93
-------
Insp.
Laboratory: ; *_^_—______^_ Init.: — Date:
Comments (Pleas* rafsr to subpart, section, or page numbers):
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
48 Revised 9/93
-------
Laboratory: ;
FORM II - DATA AUDfT REVIEW {Continued)
Insp.
Init.:
Date:
SUBPART J - RECORDS AND REPORTS
§792.185{c) - Were the amendments clearly identified with:
• reasons for change?
- date?
- signature of person responsible?
(d) Is a copy of the final report with amendments
maintained by the sponsor and the test facility?
YES
NO
N/A
REMARKS
S792.190 Storage and retrieval of records and data
(a) Where are the raw data for the study archived in
compliance with this section?
(b) Were all raw data, documentation, records, protocols,
specimens, and final reports retained which were
generated as a result of a study?
-Were all correspondence and other documents relating
to interpretation and evaluation of data, other than
those contained in the final report, retained?
(c) Are archives provided for orderly storage and expedient
retrieval of all raw data, documentation, protocols,
specimens, and interim and final reports?
- Are the conditions of the storage area appropriate to
minimize deterioration in accordance with the time
period of their retention and the nature of the
documents or specimens?
(d) Is an individual responsible for the archives?
(e) Is it specified that only authorized personnel have access
to the archives?
(f) Is the material retained in the archives indexed for rapid
retrieval?
§792.195 Retention of records
(b)
(1 ) Were records retained for at least ten years
following the effective date of an applicable final
test rule?
(2) Did the sponsor negotiate a testing agreement?
If Yes, were the data retained for at least ten years
following the publication date of the acceptance of
the negotiated agreement?
(3) In the case of testing submitted under TSCA Section
5, were records retained for at least five years
following submission to EPA?
&EPA
49
TSCA GLP INSPECTION CHECKLIST
Data Audit Review
Revised 9 93
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Insp.
Laboratory: 'nit.: Date:
Comments. (Fleas* refer to subpart, section, or page numbers):
TSCA GLP INSPECTION CHEOOJST
Data Audit Review
50 Revised 9/33
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Laboratory:
FORM • - DATA AUDfT REVIEW (Continued)
Insp.
Init.:
Date:
SUBPART J - RECORDS AND REPORTS
S792.195 (d) Are wet specimens, samples of test, control, or
, reference substances, and specially prepared material
- ' that are relatively fragile and differ markedly in stability
and quality during storage retained only as long as the
quality of the preparation affords evaluation?
(e) Were the master schedule sheet, copies of protocols,
and records of quality assurance inspections, as required
by 792.35(c), maintained by the QAU as an easily-
accessible system of records for the period of time
specified in questions 1 or 2 of this section?
(f) Were provisions in place to retain summaries of training,
experience, and job descriptions, required to be
maintained by 792.29(b), as well as all other testing
facility employment records for the length of time
specified in questions 1 or 2 of this section?
(g) Were provisions in place to retain records and reports of
the maintenance, calibration, and inspection of
equipment, as required by 792.63(b) and (c), for the
length of time specified in questions 1 or 2 of this
section?
(h) Were provisions in place to retain records required by
this part either as original records or as true copies such
as photocopies, microfilm, microfiche, or other accurate
reproductions of the original records?
YES
NO
N/A
REMARKS
EPA Library Region 4
1012061
51
TSCA GLP INSPECTION CHECKLlb r
Data Audit Review
Revised 9/93
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