&EFW
United States
Environmental Protection
Agency
Protocol for the Evaluation of Alternate Test Procedures
for Organic and Inorganic Analytes in Drinking Water
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Office of Water (MS-140)
EPA 815-R-23-002
May 2023
Questions concerning this document should be addressed to:
William A. Adams, PhD
U.S. EPA, Office of Ground Water and Drinking Water, Standards and Risk Management Division,
Technical Support Branch, 26 W. Martin Luther King Dr. Cincinnati, OH 45268
Phone:(513)569-7656
adams.william@epa.gov
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Foreword
This document provides guidelines for the evaluation of organic and inorganic contaminant analytical
methods under EPA's Drinking Water Alternate Test Procedure (ATP) Program. The Drinking Water ATP
Program only evaluates alternate methods for analytes regulated under the Safe Drinking Water Act
(SDWA), the program will not evaluate methods for unregulated or secondary contaminants.
Additionally, devices and equipment will only be evaluated as part of a complete method and not
evaluated alone. This drinking water ATP protocol provides guidance for the modification or
development of drinking water methods for compliance monitoring. It incorporates current
recommendations for method validation that have been developed by the Forum on Environmental
Measurements. Under the Drinking Water ATP Program, applicants are required to demonstrate that
the alternate method being proposed is an equally effective procedure, relative to an existing EPA-
approved method. That demonstration then provides basis for EPA's Office of Ground Water and
Drinking Water to consider, independent of the ATP evaluation, the approval a particular method.
This protocol provides basic information on the criteria the Agency generally uses in deciding whether a
method is suitable for evaluation under the Drinking Water ATP Program and the analyses that are
generally needed to demonstrate method equivalency. In this protocol, applicants are also directed to
demonstrate adequate ruggedness of the drinking water ATP through sufficient multi-laboratory
validation to support EPA's consideration of their use at a national level.
EPA anticipates that the standardized procedures described herein will expedite the processing of
drinking water ATP reviews, encourage the development of innovative technologies, and enhance the
overall utility of the EPA- approved methods for compliance monitoring under the National Primary
Drinking Water Regulations.
Disclaimer
The Office of Ground Water and Drinking Water reviewed and approved this document for publication.
Neither the U.S. government nor any of its employees, contractors, or their employees make any
warranty, expressed or implied, or assumes any legal responsibility for any third party's use of, or the
results of such use, of any information, apparatus, product, or process discussed in this protocol. The
mention of company names, trade names or commercial products does not constitute an endorsement
or recommendation for use.
This document does not alter, substitute for, establish or affect legal obligations under Federal
regulations. This document is not a rule, is not legally enforceable, and does not confer legal rights or
impose legal obligations on any federal or state agency or on any member of the public. Interested
parties are welcome to propose procedures that are different from those recommended in this
document. EPA reserves the right to change this protocol as needed.
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Table of Contents
Foreword ii
Disclaimer ii
1 Introduction 1
1.1 Background and Objectives 1
1.2 Scope of Organic and Inorganic Drinking Water ATP Process 1
2 Overview of the Drinking Water ATP Process 1
2.1 Submission (initial application and subsequent documentation) 1
2.2 Application Information 2
2.2.1 Justification for Drinking Water ATP 2
2.3 Confidential Information in Applications 2
3 Method Development and Validation Study 2
3.1 Introduction 2
3.2 Development of a Validation Study Plan 3
3.2.1 Background 3
3.2.2 Study Management 4
3.2.3 Technical Approach 4
3.2.4 Identification of Critical Steps and Plans for Addressing Critical Steps 4
3.2.5 Potential Interferences and Plans to Address Them 4
3.2.6 Sample Holding Time and Preservation 4
3.2.7 Demonstration Data 4
3.2.8 Fortified Reagent Water Analyses 4
3.2.9 Matrix Analyses 5
3.2.10 Quality Control 5
3.2.11 Draft Candidate Method 6
3.3 Approval of Validation Study Plan 6
3.4 Method Validation Study Report 6
3.4.1 Background 6
3.4.2 Study Implementation 7
3.4.3 Demonstration Data 7
3.4.4 Calculations, Data Analysis and Discussion 7
3.4.5 Conclusions 7
3.4.6 Candidate Method 7
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3.4.7 Validation Study Plan 7
4 EPA Review and Approval 7
4.1 EPA Review of Candidate Method 7
4.2 Approval Recommendation 7
4.3 Joint Drinking Water Wastewater Applications 7
Appendix A: Drinking Water ATP Applicant Process: General Checklist A-l
Appendix B: Application and Document Submission Form B-l
Appendix C: Method Validation C-l
Appendix D: Standard EPA Method Format D-l
Appendix E: Validation Report Template E-l
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uction
1.1 Backgroui tives
Pursuant to the Safe Drinking Water Act, EPA promulgates, via publication in the Federal Register, test
procedures (analytical methods) for data gathering and compliance monitoring under National Primary
Drinking Water Regulations.
Under the Agency's Drinking Water Alternate Test Procedure (ATP) Program, an organization may
request evaluation of a method as an alternate test procedure to a method already approved in the
drinking water regulations. These alternate drinking water methods, or ATPs, will be referred to as
"candidate" methods through the remainder of this document. Devices and equipment will only be
evaluated as part of a complete method and not evaluated alone. The organization or entity seeking the
candidate method evaluation is responsible for validating the candidate method. EPA evaluates test
methods used to measure regulated contaminants in drinking water and considers them for nationwide
approval. Accordingly, EPA assesses any candidate method in such a manner that its interlaboratory
range in accuracy, precision and detection capability can be compared to EPA approved test methods
measuring the same target analyte(s). To be considered for approval, the candidate method must be an
equally effective procedure, relative to the approved method (see Safe Drinking Water Act §1401(1));
that is, the method's performance characteristics in general must be equivalent to, or better than, those
of existing approved methods for the contaminant of interest. This allows EPA to ensure that data
gathered under the Safe Drinking Water Act are comparable on a nationwide basis. Those methods that
demonstrate acceptable performance through their ATP evaluation, become candidates for an EPA
approval action.
1.2 Scope of Organic and I nor; Drinking Water ATP Process
The drinking water ATP evaluation process is based on demonstrating ruggedness of a method (that is
the method yields reliable, accurate results over the range of field and lab conditions specified in the
method) and establishing equivalency of ATPs to approved methods through a comparison of
designated quality control acceptance criteria and method performance.
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Agency staff review the application, including justification for the candidate method provided by the
applicant, and determine whether a drinking water ATP evaluation is warranted. If the candidate
method application is accepted for consideration, the applicant then develops a validation study plan in
consultation with EPA's drinking water ATP staff. Once the study plan is approved, the applicant
performs the validation study (working with an independent laboratory(ies)) and submits a validation
study report and candidate method to the Drinking Water ATP Program. If laboratory validation
demonstrates performance equivalent to or better than that obtained with an approved method, EPA
Drinking Water ATP Program representatives will generally recommend approval by EPA senior
leadership using one of two options: 1) approval through the conventional "notice and comment"
rulemaking process, or 2) approval through the expedited method approval process. Find additional
information on iking water analytical methods web page. A general checklist of the drinking
water ATP process can be found in Appendix A.
2.1 Submissioin (iiniti iII i| ¦ | ¦ IIicatioin 1i -1 -""I ¦ equeint documeintatioin)
Applicants should submit drinking water ATP applications (see Appendix B) to the Drinking Water ATP
Coordinator. Upon receipt and acknowledgment of the application, EPA staff will assign an identification
number or name to the application. The applicant should use the identification number or name and
Appendix IB as a cover sheet for all future communications and any supplemental documentation
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concerning the application.
2.2 Application Information
Information required on the drinking water ATP application includes: the name and address of the
applicant; the date of submission of the application; the title of the proposed candidate method
including a shortened method name or number to use in the regulation and for reference; the analyte(s)
for which the ATP is proposed; a brief summary of the proposed method and the justification for
proposing the ATP. All required application information and any associated attachments should be
submitted for the application to be considered complete.
2.2.1 Justification for Drinking Water ATP
The applicant should provide a brief justification for why the drinking water ATP is being proposed.
Because EPA review and evaluation of proposed ATPs can entail considerable effort, EPA does not
expect to entertain evaluation of impractical methods or method modifications that fall within the scope
of flexibility already allowed in an approved method or in EPA's "Technical Notes on Drinking Water
Methods" (EPA Document No. EPA-600-R-94-173, October 1994). Examples of appropriate justifications
include but are not limited to: the candidate method successfully overcomes some or all of the
interferences associated with the approved method; the candidate method reduces the amount of
hazardous wastes generated by the laboratory; the cost of analyses or the time required for analysis is
reduced; or, the quality of the data is improved. It is highly recommended that the method developer
consult with drinking water ATP staff concerning the proposed candidate method and its justification
prior to extensive method development.
2.3 Confident >rmation iin Applications
When submitting information with the proposed drinking water ATP application, the applicant may
assert a business confidentiality claim covering part or all of the information. The method for submitting
a claim is described in the Code of Federal Regulations (CFR) at 40 CFR 2.203(b). EPA staff will handle
such information according to the regulations in subparts A and B of 40 CFR Part 2. Information covered
by such a claim will be disclosed by EPA only to the extent, and by means of the procedures, set forth in
40 CFR Part 2, Subpart B. If no such claim accompanies the information when received by EPA, it may be
made available to the public by EPA without further notice to the business.
Specifically, in accordance with 40 CFR §2.203(b), a business may assert a business confidentiality claim
covering the information by placing on (or attaching to) the information at the time it is submitted to
EPA, a cover sheet, stamped or typed legend, or other suitable form of notice employing language such
as trade secret, proprietary or company confidential. Confidential portions of otherwise non-confidential
documents should be clearly identified and may be submitted separately to facilitate identification and
handling by EPA. If confidential treatment is only required until a certain date, the notice should state so
accordingly. It should be noted, however, that any analytical method being considered for approval in
the Federal Register cannot itself be claimed as confidential business information; the method
developer must be prepared for the method to be published and made widely available.
If a claim of business confidentiality is later received after the information is initially conveyed as part of
an ATP application, EPA will make such efforts as are administratively practicable to associate the late
claim with copies of the previously submitted information in EPA files. However, EPA cannot ensure that
such efforts will be effective considering the possibility of prior disclosure or widespread prior
dissemination of the information, See §2.203(c).
3 Method Development and Validation Study
3.1 Introduction
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Method development and validation are the processes by which a laboratory substantiates the
performance of a method by demonstrating that the method can meet EPA's acceptance criteria and
that the method is rugged, that is, yields acceptable method performance and data quality over the
range of drinking water sample types and laboratory conditions specified in the method. In order to
produce a method that is rugged and meets quality control acceptance criteria, the method developer
needs to have a firm understanding of the chemistry involved in the method. Because methods vary
widely in their chemistry and procedures, no definitive global guidance can be provided on how to
develop a rugged method. In general, though, all candidate methods should: (a) identify critical points of
each step in the procedure, (b) demonstrate that these critical points are satisfactorily addressed or
controlled in the method and (c) demonstrate that acceptable method performance is attained using all
procedural options specified in the method. Generally, there is an expectation that multiple,
independent laboratories or sites be used in the validation process to ensure method ruggedness.
Critical points of a method can take a variety of forms depending on the method. For example, certain
methods may require extraction of an analyte at a specific pH or narrow pH range. Thus, for the method
to be truly rugged, pH control (for example, use of buffers) may be required to ensure that other
samples, laboratory conditions or chemists obtain satisfactory results using the method. For candidate
methods intended to be used in the field, ambient temperature may be a critical factor affecting
performance of the method. The applicant should examine and control such factors or specify the
limited conditions under which the method can be used. Other examples of critical steps requiring
ruggedness demonstration are:
• Determination of the breakthrough volume in solid phase extraction.
• Effect of laboratory temperature on a purge and trap method.
• Determination of a critical solvent-to-sample ratio in liquid-liquid extraction.
Many methods have procedural options in certain steps, for example, a choice of two sample
preservation agents. If more than one preservation option is specified in a candidate method, the
applicant must demonstrate acceptable method performance using both preservation options. Similarly,
if a candidate method specifies two different solid phase sorbents for extraction, the applicant must
demonstrate acceptable performance using both sorbents.
Once an application has been accepted by the Drinking Water ATP Program, the applicant should discuss
their plans to address method ruggedness with drinking water ATP staff prior to formulating the
validation study plan. Such consultation will help avoid both inadequate study plans (for example, not
enough analyses addressing critical points of the method) and study plans with unnecessary analyses.
The following sections summarize the major components of the validation study plan.
3.2 Development ion Study Plan
Prior to conducting the candidate method validation study, the applicant should prepare and submit a
detailed study plan for EPA approval. Guidelines describing the parameters that should be addressed in
a method validation study are provided in Appendix C. In general, the validation study plan will consist
of the following sections:
3.2.1 Background
The Background section of the validation study plan should:
• Identify the candidate method.
• Describe the reasons for development, the logic behind the technical approach and the
advantages of the method in comparison to existing technology or methodology.
• Include a summary of the candidate method.
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• List the analytes measured by the candidate method including corresponding Chemical
Abstracts Service Registry identification.
3.2.2 Study Management
The Study Management section of the validation study plan should:
• Identify the organization responsible for managing the study.
• Identify the certified (if applicable), independent laboratories, facilities, and other organizations
that will participate in the study.
• Delineate the study schedule.
3.2.3 Technical Approach
The Technical Approach section of the validation study plan should:
• Describe how participating laboratories will be selected.
• Explain who will prepare the test matrix and how it will be distributed.
• Specify the numbers and types of analyses to be performed by the participating laboratories in
accordance with this protocol.
• Identify specific reagents, materials, instrumentation, or software required.
3.2.4 Identification of Critical Steps and Plans for Addressing Critical Steps
As mentioned previously, a properly developed and validated method recognizes and controls critical
steps in terms of the chemistry or ruggedness, or both, of the method. The applicant should identify
those parts of the procedures that could be vulnerable to technician expertise or result in poorer
performance with foreseeable departures from ideal conditions. The Plan should identify the steps that
will be taken to control these critical steps.
3.2.5 Potential Interferences and Plans to Address Them
Many chemical methods are subject to chemical or physical interferences or both which, if left
uncontrolled, result in inaccurate monitoring results. Through an understanding of the chemistry of the
method, the applicant should identify potential interferences to the candidate method and plans to
address and control these interferences.
3.2.6 Sample Holding Time and Preservation
In general, candidate methods are expected to use the sample holding times, extract holding times (if
applicable) and preservation agents specified in approved EPA methods for the analyte, unless these
parameters are being explicitly modified in the candidate method. If no changes to holding times or
preservation are proposed in a given candidate method and no additional analytes are being added to a
method, then this part of the validation study plan is likely to require little discussion. However, if the
proposed candidate method alters, or could affect holding times or the preservation of the sample, a
holding time or preservation study or both will be required.
3.2.7 Demonstration Data
In this section, the applicant will specify the data to be collected using the candidate method and the
approved reference method. Generally, all candidate methods will determine precision and accuracy of
the method using both fortified reagent (laboratory) water and different real or synthetic drinking water
matrices. Synthetic drinking water matrices should be prepared to provide objective evidence of method
capabilities in a "worst case" situation (for example, high hardness or elevated ionic strength and high
total organic carbon.)
3.2.8 Fortified Reagent Water Analyses
Generally, candidate methods are required to determine precision, accuracy and sensitivity in reagent
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water fortified with the contaminant(s) of interest at relevant concentrations. Accordingly, multiple
replicates at the relevant concentration levels will be needed. Concentration levels evaluated in the
precision and accuracy studies are expected to extend both above and below the published regulatory
Maximum Contaminant Level effectively demonstrating the candidate method will satisfy all regulatory
measurement requirements. Sensitivity may be evaluated through any number of quantitation limit and
detection limit determinations. More detailed aspects of these parameters are presented in Appendix C.
Fortified reagent water samples should incorporate the preservation agent(s) specified in the method
and any other reagents or treatments specified in the method. Fortified reagent water samples should
be prepared and analyzed for every option specified in the method. For example, if two or more
preservation agents are specified as options in the method, reagent water analyses should be
independently performed using each preservation agent given in the method.
3.2.9 Matrix Analyses
For candidate methods, precision and accuracy should be examined using different drinking water
matrices that may be encountered during routine sample analysis. These drinking water matrices may
be actual or synthetic and the exact number and type needed will be determined when the validation
study plan is constructed. Generally, the matrices are a combination of the following types: (1) finished
drinking water drawn from a hard ground water source (hardness > 250 mg/L as CaC03), (2) finished
drinking water drawn from a surface water source and containing elevated total organic carbon (TOC >2
mg/L), (3) artificial drinking water matrix high in ionic strength and (4) artificial drinking water matrix
high in organic content. Additional matrices may need to be examined to document adequate
performance of the method as appropriate. For example, if chloride is known or suspected to interfere
with a given method, the validation study plan may need to include a public water supply sample or
artificial matrix having the maximum, tolerable chloride concentration that the applicant has
determined for the candidate method. If a method is designed to measure a particular disinfection
byproduct, it may be necessary to examine various finished drinking waters to adequately test the
method. Drinking water ATP staff will work with the applicant to determine appropriate matrices to
include in the validation study plan.
Analysts should review an applicable approved or published method for indications of matrix effects
that are unique to the analyte separation and measurement technologies used in the ATP. Water quality
characteristics that can affect analysis of drinking water samples include, but are not limited to, pH, total
organic carbon content, turbidity, total organic halogen content, ionic strength, sulfate, metal
contamination and trihalomethane contamination of the drinking water sample.
For each drinking water matrix specified in the validation study plan, replicates are fortified at a
concentration sufficiently below the Maximum Contaminant Level, along with a mid-level and a high-
level spike. Precision and accuracy are determined for each set of replicates. As noted above for reagent
water analyses, additional replicates or fortified concentration levels may be required depending on the
method. Also, as noted previously, each sample is tested using any and all options specified in the
candidate method.
3.2.10 Quality Control
Quality control is an important aspect of method performance. Quality control needs to be incorporated
within each candidate method and the applicant should address the quality control specified in the
method. Common quality control parameters include:
• Initial calibration and calibration verification.
• Blanks.
• Ongoing precision and accuracy.
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• Surrogate recovery.
• Internal standard response.
• Fortified matrix precision and accuracy.
Appendix C, Table 1 summarizes the above quality control parameters as they are addressed for organic
and inorganic contaminants in EPA drinking water methods.
3.2.11 Draft Candidate Method
A draft of the candidate method should be included as a separate attachment to the validation study
plan. The draft details the step-by-step procedures of the candidate method. This includes all
equipment, reagents and materials required and data evaluation or calculation procedures. Unless the
applicant is a consensus standards organization or government organization that has their own method
format requirements, all applicants should submit the candidate method written in the standard EPA
method format (Appendix ID). Applicants from organizations having their own format requirements
should compare their specific method format with the EPA method format to ensure that all sections of
the EPA method format are addressed. The 17 sections listed in Appenc of this document should be
included for all candidate methods. Recent drinking water methods published by EPA (for example,
Methods 150.3, 533, 546) may also be consulted for format and the level of detail required.
3.3 Approval of Validation Study Plan
Once EPA is satisfied that the written method and the proposed study plan meet the criteria described
in this document, the applicant will be instructed to proceed with the method validation study.
;thod Validation Study Report
The applicant should document the results of the validation study in a formal validation study report
containing the elements described in this section. In all cases, a copy of all required validation data
should be maintained at the laboratory or other organization responsible for developing the method.
The information and supporting data in the validation study report must be sufficient to enable EPA to
determine whether the candidate method performs as well as or better than the approved reference
method.
The validation study report should contain background information and describe the study design. In
addition, the validation study report should detail the process and results of the study, provide an
analysis and discussion of the results, and present study conclusions. The approved validation study plan
should be appended to the validation study report and referenced as appropriate.
The validation study report should identify and discuss any deviations from the validation study plan
that were made in implementing the study along with problems encountered and corrective actions. To
the extent possible, deviations should be discussed with EPA in advance of being implemented to ensure
that the deviations are appropriate.
See Appendix IE for the validation study report template.
3.4.1 Background
The Background section of the validation study report describes the candidate method. The Background
section of the validation study report should:
• Include a method summary.
• Summarize the justification for the ATP evaluation and the proposed benefits the candidate
method offers to drinking water monitoring.
• List the analytes measured by the candidate method, including corresponding Chemical
Abstracts Service Registry identification.
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3.4.2 Study Implementation
The Study Implementation section of the validation study report describes the methodology and
approach undertaken in the study. This section should:
• Identify the laboratories or other organizations or both that participated in the study.
• Delineate the study schedule that was followed.
• Explain how samples were collected and handled.
• Specify the numbers and types of analyses performed by the laboratory.
• Identify any problems encountered or deviations from the study plan and their resolution or
impact on study performance or results or both.
3.4.3 Demonstration Data
This section of the validation study report should include the demonstration data for the analyzed
samples. For each sample, the report should compare method performance data obtained with the
candidate method to the approved reference method performance data. Demonstration data should be
provided for samples using all procedural options specified in the method.
3.4.4 Calculations, Data Analysis and Discussion
This section of the validation study report should provide sufficient documentation of the data obtained
with the candidate method to permit an independent reviewer to verify the study results. Example
calculations are required as part of the results and should be included in the validation study report. The
test data and calculations should be electronically reported in a format compatible with Microsoft®
Office applications. The discussion should address any discrepancies between the results and the quality
control acceptance criteria.
3.4.5 Conclusions
The Conclusions section of the validation study report describes the conclusions drawn from the study
based on the data analysis discussion. The Conclusions section should contain a statement(s) regarding
achievement of the study objective(s).
3.4.6 Candidate Method
The candidate method should be appended to the validation study report. Format should follow that
specified in Appendix D.
3.4.7 Validation Study Plan
The validation study plan should be appended to the validation study report.
4 I I i r I1"' ! ! . J I I ! I
II II II II eviiew oil - .ill-Hi-II ite Method
EPA's Drinking Water ATP Program reviews the candidate methods and the validation data. If a
candidate method is determined to provide equivalent method performance relative to the reference
method, it becomes a candidate for approval by EPA senior leadership.
4.2 Appro ;oinn inn ein clatii oin
EPA will complete its review and notify the applicant of EPA's recommendation. If the candidate method
is recommended for approval, EPA will pursue formal approval using one of two options: 1) approval via
the conventional "notice and comment" rulemaking process or 2) approval via the expedited method
approval process. Find additional information on EPA's drinking water analytical methods web page .
4.3 Joint Drinking Water Wastewater Applications
Candidate methods can be submitted for ATP evaluation used for both drinking water and wastewater
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applications. However, the requirements for compliance monitoring under the National Primary
Drinking Water Regulations differ from those under the National Pollutant Discharge Elimination System
permit program. Review and evaluation of ATP candidate methods that are submitted for dual
applications are thus handled by both the Drinking Water ATP Program and the Wastewater ATP
Program.
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Step 1: Initial Inquiry
Y
N
N/A
Notes
The application includes name, address, date, and title of the proposed
method.
The proposed method is for drinking water and the analysis of regulated
contaminants or water quality parameters.
The EPA has assigned a unique identifier to the submitted method.
The applicant has included method data with their request (optional).
The EPA has determined the request is allowed within the method-specified
flexibility.
The EPA has determined an evaluation of the proposed method as an ATP
candidate method is warranted.
Step 2: ATP Initial Application
Y
N
N/A
Notes
The applicant has provided the Application and Document Submission Form
with all requested information.
The application includes the analyte to be studied.
The application lists the approved EPA reference method(s) used for
comparison with the candidate method.
The applicant has submitted justification for the candidate method to the
Drinking Water ATP Coordinator.
The applicant is asserting a claim the candidate method contains confidential
business information (CBI).
The applicant has attached paperwork pursuant to 40 CFR 2.203(b) regarding
CBI.
The applicant has submitted and separated the CBI and indicated with an
appropriate coversheet marked "confidential."
The EPA has handled CBI pursuant to subparts A and B of 40 CFR Part 2.
Step 3: Submission of Study Plan
Y
N
N/A
Notes
The study plan cover sheet includes name, address, date, case number, and
title of the proposed method.
A draft of the candidate method has been provided.
The applicant has identified the critical points of the study proposal.
The applicant has discussed methods to control the critical points of the
proposal.
The applicant has included experiments to verify all procedural options
specified in the method.
The applicant has included in their validation study plan a discussion to
address method ruggedness.
The applicant has submitted a complete validation study plan to EPA for
review following the ATP protocol guidelines.
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Step 3: Submission of Study Plan
N/A
Notes
The background of the study plan includes a summary of the candidate
method.
The background of the validation study plan includes a list of the analytes
and corresponding Chemical Abstracts Service (CAS) Registry identifications.
The validation study plan identifies the organization responsible for
managing the study.
The validation study plan identifies the laboratories/organizations that will
participate in the study.
The validation study plan contains and assigns a study schedule to the
laboratories/organizations participating in the study.
The validation study plan uses the same holding times, extract holding times,
and preservation agents specified in the candidate method.
The validation study plan lists all the equipment that will be used in the
candidate method.
The validation study plan lists all the reagents that will be used in the
candidate method.
The validation study plan includes all 17 sections of the EPA method format.
The validation study plan identifies critical steps and the plan to monitor and
account for departures from method performance.
The validation study plan identifies interferences (chemical, physical) that
may affect the results and the plans to mitigate the interferences.
The validation study plan includes a method to determine precision and
accuracy using fortified reagent water.
The validation study plan includes a method to determine effectiveness
above and below the Maximum Contaminant Level (MCL).
The validation study plan includes a method to incorporate the preservative
agent(s) into fortified reagent water as identified in the method.
The validation study plan includes analysis of drinking water from a hard
water source. (Optional)
The validation study plan includes
that contains total organic carbon
analysis of drinking water from a source
> 2mg/L. (Optional)
The validation study plan includes analysis of artificial drinking water with a
high ionic strength. (Optional)
The validation study plan includes analysis of artificial drinking water with a
high organic content. (Optional)
The validation study plan includes analysis of artificial drinking water with a
high chloride content. (Optional)
The validation study plan includes analysis of artificial drinking water with a
disinfection byproduct. (Optional)
The validation study plan includes an analysis of the Quality Control Targets
used in the candidate method.
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Step 4: Submission and Review of Method Validation Study Report (MVSR)
Y
N
N/A
Notes
The background of the MVSR contains a method summary, justification for
the ATP evaluation, and a list of the analytes.
The MVSR study implementation section identifies the
laboratories/organizations that participated in the study.
The MVSR implementation report lists the study schedule that was followed.
The MVSR study implementation section explains how the samples were
collected and handled.
The MVSR implementation section specifies the types and numbers of
analyses to be performed in the lab.
The MVSR implementation report identifies and describes any deviations or
problems that impacted the study performance.
The MVSR presents a sufficiently detailed version of the candidate method in
the correct EMMC format.
The MVSR contains sample calculations.
The test data is reported in a format compatible with Microsoft® Office
applications.
The MVSR contains a discussion of discrepancies between results and quality
control acceptance criteria.
The MVSR contains a conclusion section discussing achievement of the study
objective(s).
The MVSR contains the approved validation study plan in the appendix.
Developed in collaboration with EPA, the MVSR contains data from multiple
matrices to identify interferences or matrix effects.
Step 5: Data Review of MVSR by EPA
Y
N
N/A
Notes
Applicant has completed the Application and Document Submission Form.
The applicant has submitted evidence of instrument calibration.
The applicant has submitted a rigorous evaluation of bias in their analytical
method.
The applicant has submitted an evaluation of precision, using the extremes
of the quantitation range, regulatory levels, and multiple matrices.
The method blank meets the minimum reporting level (MRL) described in
the reference method (if applicable).
The results from the initial demonstration of capability (IDC) passes the
Quality Control Targets used in the candidate method.
The method demonstrates chemical and microbiological storage and
stability.
The method has utilized a minimum number of sites/laboratories for data
collection, as determined by the EPA.
Step 6: Final Evaluation by EPA
Y
N
N/A
Notes
The applicant has demonstrated through design, experiment, and data
collection that their candidate method is rugged.
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Step 6: Final Evaluation by EPA
Y
N
N/A
Notes
The applicant has submitted any additional paperwork and data requested
by the EPA.
The EPA has satisfactorily protected the CBI of the applicant.
The EPA has determined the candidate method as ab ATP submission is
equally effective as the reference method.
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EPA Office of Ground Water and Drinking Water
Alternate Test Procedure Candidate Method Application
~ Initial Application
~ Supplemental Documentation
~ Final Application
Applicant Information
Applicant Name:
Address:
State:
Zip Code:
Contact name:
Phone number:
Email address:
Submission Date:
Candidate method:
Analyte(s):
Candidate method title:
Reference method number or name or both:
Attachments
~ Justification for Candidate Method
~ Candidate Method
~ Validation Study Plan
~ Validation Study Report
~ Raw Data Package (spreadsheets, calibrations, etc.)
~ Data Collection Certification
~ Other Documentation:
EPA use only Case number:
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1 11 ii! 0< ''u< ||.>|i
Method validation is the process of demonstrating that an analytical method is suitable for its intended
use and involves conducting a variety of studies to evaluate method performance under defined
conditions. Method validation studies may involve a single laboratory (intralaboratory) or multiple
laboratories (interlaboratory). The goal is to demonstrate that analytical results produced by the
application of a particular method are fit for an intended purpose. Properly designed and successful
method validation studies create confidence in the reliability of a test method. Method validation is one
of several important quality system components that are designed to ensure the production of
scientifically valid and useful analytical data.
The information in this appendix is intended to serve as a guideline only. Because methods vary
significantly in chemistry and technology, it is not possible to define a single set of performance criteria
that can be applied to all methods. This is due to the severe problems in translation of a complex
domain of knowledge such as analytical chemistry into a mathematical statement. This appendix lists
critical elements of the general method validation process that may not apply in all cases. The actual
validation components that will be necessary will be determined during the creation of the method
validation study plan.
2 Storage Stability
Before validating an analytical method, it is necessary to ensure that proper sample preservation and
storage stability studies were performed during method development. Storage stability should
investigate the stability of the analyte(s) from the time of sampling through the time of analysis. If an
extraction is performed, the extract stability should also be investigated. Analytes may be lost through
volatilization, sorption, chemical degradation (abiotic reactions) and microbial degradation
(microorganisms have the potential to degrade target analytes and represent a significant pathway for
the fate and destruction of organic compounds).
3 Instrument Calibration
Instrument calibration refers to the procedures used for correlating instrument response to an amount
of analyte (concentration or other quantity). The characteristics of a calibration function and
justification for a selected calibration model should be demonstrated during a method validation study.
The performance of a calibration technique and the choice of calibration model (for example, first order,
second order, weighting, etc.) are critical for minimizing sources of instrument bias and optimizing
precision. The parameters of the model are usually estimated from the responses of known, pure
analytes. Calibration errors can result from failure to identify the best calibration model; inaccurate
estimates of the parameters of the model; or inadequately studied, systematic effects from matrix
components.
During method development and validation, calibration models are typically evaluated by analyzing
multiple levels of calibration standards over a selected working range. After a calibration curve is
constructed from the responses, the concentrations of the standards are calculated from the curve.
These values are then compared to the appropriate quality control criteria to determine the curve's
adequacy. The calibration study results should be included in a method validation report. Access to
information about calibration performance characteristics assists the user in implementing new
methods and verifying that a laboratory's instrument performance is acceptable.
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4 Accuracy
Bias refers to the overall magnitude of known systematic (determinate) errors associated with the use of
an analytical method. The presence of systematic errors can only be determined by comparison of the
average of many results with a reliable, accepted reference value. Method bias may be estimated by
measuring materials whose composition is reasonably well known or by analyzing fortified materials.
Rigorous evaluations of bias should be included in method validation studies. Minimally, bias should be
evaluated at the extremes of the quantitation range, at regulatory levels and in representative matrices.
The most common measure of bias is the calculation of a percent recovery.
5 Precision
The general term "precision" is used to describe the magnitude of random (indeterminate) errors
associated with the use of an analytical method. The sources of random error evaluated depend upon
the range of conditions over which the data are collected.
Precision should be evaluated at the extremes of the quantitation range, at regulatory levels and in
representative matrices. Common measures of dispersion are the standard deviation and the percent
relative standard deviation of repeated measurements. The repeatability and reproducibility conditions
should be clearly stated so that the measures of dispersion can be properly interpreted and evaluated.
6 Quantitation Limits and Range
The term "quantitation range" is used to describe the span of analyte levels, as contained in a sample
matrix, for which method performance has been tested and data quality is deemed acceptable for its
intended use. For compliance, a quantitation range includes either a regulatory or other type of action
level for the compound being analyzed.
A lower limit and an upper limit bound a quantitation range. A quantitation range may be wider than an
instrument's calibration range because of dilution or concentration steps performed during sample
preparation. Dilution factors or concentration factors are used to relate the calibration range to the
quantitation range. Analyte concentration will influence most method performance characteristics,
including accuracy and precision. At a minimum, method accuracy and precision should be evaluated at
the extremes of the quantitation range.
The lower limit of the quantitation range is commonly referred to as the "limit of quantitation." The
minimum reporting level (MRL), or the minimum concentration that can be reported by a laboratory as a
quantified value for the method analyte in a sample following analysis, should always be above the
"limit of quantitation" and both should be at or above the lowest calibration standard.
7 Detection Limit(s)
The term "detection limit" is used to describe the lowest concentration at which the presence of an
analyte can be confidently determined. There are many specific definitions for this term, and it is used
to describe the detection capabilities of detectors, instruments, and analytical methods. In lieu of
detection limits, analysts have also used MRLs and performed MRL confirmations (that may be included
in the methodology) as a demonstration of their capability to achieve a required MRL. In those cases
where Method detection limits (MDLs) are specified in regulation, the procedure associated with that
specification (e.g., 40 CFR, Part 136, Appendix B) must be used to determine them.
8 R u gge d n e s s Te st i n g
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Ruggedness refers to the extent to which an analytical method remains unaffected by minor variations
in operating conditions. Ruggedness testing involves experimental designs for examining method
performance when minor changes are made in operating or environmental conditions. The changes
should reflect expected, reasonable variations that are likely to be encountered in different laboratories.
Ruggedness testing is generally conducted at the end of method development but before an
interlaboratory method validation study.
1 11 lu:y ! .t! I I i ¦ ! ! ii I s i ii I il11 ivelopment
As previously mentioned, the necessary validation components will be determined during the creation
of the method validation study plan. This includes the numeric limits for specific quality control
parameters. These values will depend on the regulation, intended data use, the quality control
parameters for existing reference methods and the individual technology that is being applied. Table 1
provides reference values that are generally used by Office of Ground Water and Drinking Water for
method development.
Table 1. Reference Values generally used for Drinking Water Method Development
Parameter
Organic Methods
Inorganic Methods (Ion
Chromatography or
wet)
Metals or Inductively
Coupled Plasma
Method Blank
<1/3 MRL
<1/3 MRL
<1/3 MRL
Initial Demonstration of
Capability Accuracy or
bias, Continuing
calibration checks and
Calibration curve checks
(as %recovery)
>2 x MRL ± 30%, <2x
MRL ±50%
>2 x MRL ± 15%, <2x
MRL ±20%
>2 x MRL ± 10%, <2x
MRL ±20%
Surrogate Recovery
±30%
± 15%
Not Applicable
Initial Demonstration of
Capability Precision and
Duplicate Samples (%
Relative Standard
Deviation)
±30%
± 20%
± 15%
Internal Standard
>50% of the Internal
Standard area or
response in the active
calibration
Same
60%-125%
Additionally, the typical validation study would involve the method being evaluated by three
laboratories, at least two of which are independent (i.e., free of conflict of interest) and, if applicable,
certified (i.e., certified by the primacy agency [typically the state] for the analysis of compliance
monitoring samples for the analytes of interest).
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Appendix D: .Standard EPA Method Format
[Note: Each method should be a free-standing document, providing all information necessary for the
method user to perform the analysis. References within a method should be restricted to associated or
source material. Procedural steps or instructions should not be referenced as being found elsewhere but
should be included in totality within the method. The following section numbering scheme is typical
with the Environmental Monitoring Management Council (EMMC) format.]
'>" Scope ,.|k! < }.1 !h"I""'¦' 1"¦ "¦!!i
[This section outlines the purpose, range, limitations, and intended use of the method and identifies
target analytes.]
11 .Summary of Method
[This section provides an overview of the method procedure and quality assurance.]
I " [' 11|.III !!.
[This section includes definitions of terms, acronyms and abbreviations used in the method. If preferred,
definitions may be provided in a glossary at the end of the method or manual. In this case, the
definitions section should still appear in the method, with a notation that definitions are provided in a
glossary (refer to the specific section number of the glossary) at the end of the method.]
13 Interferences
[This section identifies known or potential interferences that may occur during use of the method and
describes ways to reduce or eliminate these interferences.]
14 Safety
[This section describes special precautions needed to ensure personnel safety during the performance
of the method. Procedures described here should be limited to those which are above and beyond good
laboratory practices. The section should contain information regarding specific toxicity of analytes or
reagents.]
15 Equipment and Supplies
[This section lists and describes all non-consumable supplies and equipment needed to perform the
method.]
1 S >!!. I I >!!. I >!! J!
[This section lists and describes all reagents and standards required to perform the method and provides
preparation instructions or suggested suppliers or both as appropriate.]
I / ¦ HI.-' Ii-Mi I !! 1 ~!! .Ii.Mi > < 11 ' \c\ .; r
[This section provides requirements and instructions for collecting, preserving, and storing samples.]
18 Quality Control
[This section cites the procedures and analyses required to fully document the quality of data generated
by the method. The required components of the laboratory's quality assurance program and specific
quality control analyses appropriate to the method are described in this section. It should at least
address the quality control specifications listed in Appendix C, Table 1 of this document.]
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19 Calibration and .Standardization
[This section describes the method or instrument calibration and standardization process and the
required calibration verification. Corrective actions are described for cases when performance
specifications are not met.]
I ! ii >i
[This section describes the sample processing and instrumental analysis steps of the method and
provides detailed instructions to analysts.]
I I It s. It / n J- , i , i!,! J! ¦ J. nl til'"!!
[This section provides instructions for analyzing data, equations, and definitions of constants used to
calculate final sample analysis results and their uncertainties.]
Mill i I ! I ! ! I ! I
[This section provides method performance criteria for the method, including precision or bias
statements regarding detection limits and sources or limitations of data produced using the method.]
23 Pollution Prevention
[This section describes aspects of the method that minimize or prevent pollution known to be or
potentially attributable to the method.]
24 ^
[This section describes minimization and proper disposal of waste and samples.]
25 References
[This section lists references for source documents and publications that contain ancillary information.]
« I i •! il "! !! !!' I !! !! > ! I \ k.| I ' Jl
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Appendix E: Validation Report Template
Microsoft® Word
This template is to be used to prepare final validation study reports for ATPs. The template sets up the
primary validation study report sections along with brief instructions for each section. The template is
prepared using an Adobe®-supported font for proper .pdf conversion. Please do not make any changes
to fonts or styles.
If the alternate test method demonstrates equivalency to an approved method, EPA may subsequently
approve the method for compliance monitoring through either conventional notice-and-comment
rulemaking or through the expedited methods approval process. In either case, this validation report will
be incorporated in the public docket associated with the approval action.
If typing the validation study report directly into the template, replace the text of the template and
begin typing your report (that is, select the Title section and replace it with your title). This page of
instructions can be deleted upon completion of the validation study report.
Insert graphics within the text in TIFF, JPEG or Microsoft® Office compatible file format (*.wmf or
*.emf).
Save the file with the graphics in place as a document file (.doc).
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Alternate Test Procedure (ATP) Validation Study Report
Title
[The title should clearly and concisely specify the name of the method, the scope of the measurement
(for example, "measurement of turbidity", "nitrate analysis", etc.) and the instrumentation (if
applicable). The title should also include a shortened method name or number to use in the regulation
and for reference]
Date
Name and address of organization
Author name(s)
[Include individual(s) with responsibility for overseeing development of the alternate test method and
verifying accuracy of the data presented in the validation study report. Designate the appropriate point
of contact in the event questions arise after review of the report.]
Phone number and email address
[Author or point of contact phone number and email address.]
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1 Bac"
[Provide a method summary discussing the experimental technique.]
1.1 M et Ih o d J u st i fi c a t i o in
[Specifically cite the approved method (including revision/version) that the candidate method is being
compared to, the organization where the approved method originated (for example, ASTM, Standard
Methods, EPA, etc.), and the method number. Summarize justification for the candidate method and
describe the advantages relative to the approved method, especially in terms of improved sample
throughput, reduction of hazardous waste, cost reduction, elimination of interferences, etc.]
1.2 Method Equivalency
[Summarize the quality control acceptance criteria as defined in the approved method and describe how
the candidate method meets these specifications. Clearly indicate in the final sentence whether the
candidate method is "equally effective" in meeting quality acceptance criteria as the approved method.]
1.3 Ana llytes
[Identify the analytes that are determined using the candidate method and list the corresponding
Chemical Abstracts Service registry numbers.]
2 Study Implementation
[Clearly identify the managing organization responsible for development of the candidate method
validation study plan and all of the laboratories participating in the study. Explain why specific
laboratories were selected to participate and address any potential for conflict of interest. Identify
whether the study involved the use of different types of instrumentation (for example, gas
chromatography-mass spectrometry analyses using ion trap detectors and triple quadrupole
detectors).]
2.1 Study Schedule
[Delineate the study schedule.]
2.2 Sample Collection
[Describe how samples were collected and handled. Specify whether required holding times were met.]
2.3 Types of Analyses Performed
[Describe the number and types of analyses performed by each laboratory (for example, specify how
many replicate analytical runs were performed to evaluate precision and accuracy in each drinking
water matrix, incorporation of blanks, etc.]
2.4 Study Plan Deviations
[Fully describe any problems encountered or deviations from the study plan and the resolution or
impact of these issues on the study plan performance results.]
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3 Method Procedure and Data
[The candidate method should be prepared in standard EPA EMMC-method format and submitted with
the initial validation study plan. In this final validation report, the method should be attached as an
addendum and referenced as such in this section. Compare and contrast procedural differences
between the candidate method and the approved method.]
3.1 Validation Study Demonstration Data
[Submit complete demonstration data for both reagent water and drinking water matrix analyses in
tables, graphs, or figures, as appropriate. The data should clearly present the candidate method data in
comparison with the required reference method quality control criteria. Address the items in the
following subsections, as appropriate.]
3.1.1 Calibration
[Demonstrate acceptable calibration performance as defined in the validation study plan. Include
calibration verification through incorporation of calibration checks.]
3.1.2 Initial Demonstration of Capability
[Demonstrate acceptable low system background, precision and accuracy and detection limit or
minimum reporting level confirmation (as specified in the validation study plan).]
3.1.3 Quality Controls
[Include verification of method performance using blanks, surrogates, internal standards, and other
quality controls as specified in the validation study plan.]
3.1.4 Precision and Accuracy
[Include all precision and accuracy data for reagent water and drinking water matrix samples.]
3.2 Holding Time or Storage Stability
[If specified in the validation study plan, submit storage stability data. Otherwise, indicate that a holding
time study was not required.]
4 Data Analyji il -i
[Provide a comparison of the candidate method data to the approved method to confirm equivalency of
performance. Discuss in detail any discrepancies between the results and quality control acceptance
criteria. Discuss method ruggedness based on overall performance as specified in the validation study
plan (for example, multi-laboratory studies, analyses performed on multiple instruments, assessments
of various drinking water matrices, etc.)]
5 Conclusions
[Discuss achievement of validation study objectives.]
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il. ! 1 ! ! I I I II I I ?! ijl > , ' Jl J! ,1!' 1! i! 11 'J! I I t!! i
[Append the approved validation study plan.]
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il. ! 1 ! ! I I I II I I f! ijl > p.. • I '{>{>• !! S11. il ' ,1 ,
Raw Data
[Submit raw data in an excel spreadsheet. Identify instruments used and operating conditions,
chromatographic column specifications, high-performance liquid chromatography gradients, gas
chromatography temperature programs, detectors, injection volumes, solid phase extraction media and
extraction procedures.]
Example Calculations
[Provide sample calculations to verify that the laboratory has used the raw data to correctly arrive at the
final results.]
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h. ! | ! I I I I ! ! ! 1 [ N III, ! I li I. '»!!!!. ¦! i
It is the expectation of the ATP program that all data will be collected as outlined in the validation study
plan. Applicants must attest on the application that the data collection was performed as outlined in the
validation study plan.
The applicant hereby certifies that the data included with this application were collected as outlined in
the validation study plan.
Applicant (print name)
Applicant (signature) and (Date)
[Questions, comments, or applications should be directed to:
William A. Adams, PhD.
U.S. EPA, OGWDW, TSC
26 W. Martin Luther King Dr. Cincinnati, OH 45268
Phone: (513) 569-7656
adams.william@epa.gov
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