US Environmental Protection Agency Office of Pesticide Programs Office of Pesticide Programs Microbiology Laboratory Environmental Science Center, Ft. Meade, MD Quality Management Plan (QMP) - 2011 July 2011 ------- Quality Management Plan 2011 Office of Pesticide Programs Biological and Economic Analysis Division Microbiology Laboratory Branch ------- PREPARED BY: NAME: KiranVerma TITLE: Quality Assurance Officer, Microbiology Laboratory Branch SIGNATURE: DATE: CONCURRENCES: NAME: Susan Lawrence TITLE: Branch Chief, Microbiology Laboratory Branch SIGNATURE: DATE: NAME: DeniseRice TITLE: OPP Director of Quality Assurance SIGNATURE: DATE: BEAD/MLB July 2011 Page 2 of 38 ------- BEAD/MLB July 2011 Page 3 of 38 A. PROGRAM OVERVIEW I. Antimicrobial Testing Program (ATP) 5 II. Plant Incorporated Protectant Program 5 III. Homeland Security Research 6 IV. CDC Select Agent Research 9 V. Biofilm 9 VI Virology Testing Program 9 B. MANAGEMENT AND ORGANIZATION I. General Organizational structure 10 II. Mission 11 III. Policy on Quality Assurance 11 IV. Responsibilities 12 V. Resource Allocation 15 C. QUALITY SYSTEM AND DESCRIPTION I. Principle Components 16 II. Process 17 D. PERSONNEL QUALIFICATION AND TRAINING I. Policy 21 II. Qualifications and Training 21 III. Proficiency Testing /Uncertainty 22 E. EXTRAMURAL AGREEMENTS AND PROCUREMENT OF ITEMS AND SERVICES 24 F. DOCUMENTS AND RECORDS I. Process for Recording and Maintaining Data 26 II. Quality Assurance Records 27 III. Archives and Disposition 27 G. COMPUTER HARDWARE AND SOFTWARE 27 H. PLANNING 28 I. IMPLEMENTATION OF WORK PROCESSES 29 J. ASSESSMENT AND RESPONSE 30 K. QUALITY IMPROVEMENT 31 L. REFERENCES 31 M. LIST OF APPENDICES 33 ------- BEAD/MLB July 2011 Page 4 of 38 A. Program Overview The Office of Pesticide Program's (OPP), Biological and Economic Analysis Division (BEAD), Microbiology Laboratory Branch (MLB) provides microbiological laboratory services to the Program office and other federal and state partners necessary to support pesticide regulatory and enforcement programs. The laboratory's current initiatives include the evaluation of the efficacy of antimicrobial pesticides, method development for antimicrobials including new product types and emerging pathogens, evaluation of a new quantitative efficacy test method for a wide range of microorganisms (to support harmonization of efficacy data across OECD member countries), and support to the EPA Office of Emergency Management for verification of a rapid viability PCR based method for detection of bio-threat agents in environmental samples. A significant component of the laboratory's mission is the evaluation of the efficacy of antimicrobial products with public health claims that are registered by the EPA- products used to kill or suppress the growth of infectious microorganisms on inanimate objects and surfaces. Standard methods, such as those published by AOAC or ASTM, are used by the laboratory to monitor the efficacy of hospital disinfectants and tuberculocides currently registered by the Agency. The laboratory works to improve the current methods by developing data to support editorial and procedural modifications. Development and adoption of new quantitative test methods used to determine the efficacy of antimicrobials is a key priority. Bio-threat agents, such as anthrax, as well as emerging public health pathogens present new challenges in the regulatory and enforcement arenas. Decontamination and remediation of sites contaminated with bio-threat agents has lead to the laboratory's role in the development of suitable methods and surrogates for evaluating antimicrobial products for Homeland Security purposes. The laboratory is working closely with the EPA Office of Research and Development (ORD) and other federal partners to meet the Agency's Homeland Security needs. The laboratory has developed contractual agreements and interagency agreements to leverage laboratory resources. Various studies are underway to enable the Program to regulate antimicrobial products used for Homeland Security purposes. In FY 2009, the laboratory established the capacity to test viruses (Virucidal Testing Program). Equipment, supplies, materials, space and personnel were allocated to support this effort. The initial test system uses feline calicivirus as a surrogate for human norovirus. Human noroviruses are the leading cause of outbreaks for non-bacterial gastroenteritis worldwide and cannot be grown in laboratory, thus the need to test surrogates. It is anticipated that the laboratory will continue to invest in additional cell line/virus combinations as necessary to evaluate label claims for antimicrobials in the future. The laboratory is also working on new pathogens, such as Clostridium difficile, and has invested time in the evaluation of methods for growing and treating bacterial biofilm. Developing suitable growth and recovery media to achieve sufficient liters for evaluating new microorganisms, evaluating technique sensitive steps and quality control procedures, and ------- BEAD/MLB July 2011 Page 5 of 38 addressing other method specific issues is underway. The laboratory adds new programs as the needs of the Office change in order to meet the regulatory mandates. The Microbiology Laboratory Branch is located at Environmental Science Center, Fort Meade, MD. The Environmental Science Center houses Region 3 and Office of Pesticide Programs laboratories, technical and support personnel. The MLB wing includes Biosafety Level 2 and 3 laboratories necessary to conduct work with pathogenic microorganisms. The laboratory is registered under the Centers for Disease Control and Prevention (CDC) Select Agent Program. I. Antimicrobial Testing Program (ATP) This program was initiated in response to findings presented by the Government Accounting Office (GAO) that the EPA lacked assurance that antimicrobial products registered by the Agency were efficacious. EPA has focused its efforts on evaluating registered products that are most crucial to infection control (sterilants, tuberculocides, and hospital-level disinfectants). The manufacturer of any product bearing a public health claim is required to submit efficacy data to the Antimicrobials Division (AD) of OPP to substantiate the product's effectiveness and AD evaluates and registers antimicrobials. OPP's Microbiology Laboratory Branch, in conjunction with three state laboratories, perform efficacy tests using the same parameters (contact time, dilution of product) as noted on the product label or registration data. The client, the Antimicrobials Division (AD), defines the testing criteria. If testing demonstrates that a product does not provide acceptable levels of control of target microorganisms, EPA's Office of Regulatory Enforcement may take action against the manufacturer. The Agency has completed testing of sterilant products, and is currently testing approximately 800 EPA- registered hospital-level disinfectants and 150 tuberculocides. The laboratory uses standard methods such as those published by AOAC International and ASTM International (American Society for Testing and Materials) and Standard Operating Procedures (SOPs) to determine the efficacy of hard surface disinfectants against infectious microorganisms. The laboratory's Standard Operating Procedures (SOPs) for testing, quality control, and equipment calibration can be accessed at the web site: http://www.epa.gov/oppbeadl/methods/atmpindex.htm. The laboratory's scope of accreditation under ISO 17025 includes the standard methods used to evaluate disinfectants and tuberculocides under this program. The laboratory's accreditation certificate and scope of accreditation issued by A2LA once available will be posted on the laboratory website. It is not anticipated that additional advertising with respect to the ISO 17025 accreditation status of the laboratory will be required. If management determines that additional advertising is necessary, the laboratory will follow the current A2LA Advertising Policy with respect to the activities under the scope of accreditation and use of the A2LA symbol (P101 - Reference to A2LA Accredited Status, A2LA Advertising Policy). II. Plant Incorporated Protectant (PIP) Method Validation Program EPA regulates Plant Incorporated Protectants (PIP) materials that enable a plant to protect ------- BEAD/MLB July 2011 Page 6 of 38 itself from pests such as insects, viruses and fungi by producing its own pesticide. The Biopesticides and Pollution Prevention Division (BPPD) is responsible for regulating PIPs. A PIP plant in the field, however, cannot be distinguished visually from a conventional plant. So, current PIP registration guidelines require registrants to submit a method for the detection of the unique PIP DNA sequence, as well as a method to detect the protein expressed by that unique DNA sequence. OPP's Microbiology Laboratory validates detection methods submitted with registration applications. The registrant's methods and an Independent Laboratory Validation (ILV) are provided to the laboratory by the client and serve as the basis for the method validation study. This program is not currently active but the equipment and Standard Operating Procedures are available if method validation is required in the future. III. Homeland Security Research OPP has the responsibility for regulating antimicrobial products, including sporicides, used to treat and decontaminate inanimate surfaces. BEAD'S Microbiology Laboratory Branch (MLB) is responsible for conducting testing of antimicrobial products to ensure products are effective. The Laboratory's resources and expertise are also well suited to meet ongoing Homeland Security needs for improved and standardized efficacy test methods to ensure that decontamination products are effective in inactivating bioterrorism agents. Homeland Security Presidential Directive 10 directs EPA to take the federal lead for "developing specific standards, protocols, and capabilities to address the risks of contamination following a biological weapons attack and developing strategies, guidelines, and plans for decontamination of persons, equipment, and facilities." EPA's Office of Chemical Safety and Pollution Prevention (OCSPP) is addressing this directive to significantly improve the nation's ability to treat contaminated sites and to allow for safe re-occupancy. Developing proven standard methods for evaluating and testing the effectiveness of antimicrobial decontamination products, such as those used to decontaminate facilities contaminated in 2001 with spores of Bacillus anthracis (anthrax) is critical for protecting public health. In response to this directive, the OPP MLB is spearheading an effort to update and improve the quality of existing regulatory test methods and to validate new quantitative procedures to determine the performance of antimicrobial pesticides. Test methods for testing non-spore forming bio-threat agents such as Francisella, Yersinia and Brucella are also covered under this project. In July 2007, an EPA Scientific Advisory Panel (SAP) was convened on the guidance on test methods for demonstrating efficacy of antimicrobial products (sporicidal decontaminants) for inactivating B. anthracis spores. As an outcome of the meeting, the SAP provided a number of suggestions on the selection of surrogates and coupon materials. A key priority related to the Agency's Homeland Security efforts has been the evaluation and development of quantitative methodology to replace or augment qualitative methods such as the AOAC Use-dilution method and AOAC method 966.04, Sporicidal Activity of Disinfectants. Data generated from AOAC Method 966.04 are more relevant to clinical settings than decontamination scenarios involving buildings and environmental surfaces. As a component of a ------- BEAD/MLB July 2011 Page 7 of 38 short-term strategy to address federal regulatory needs, several technical limitations associated with AOAC Method 966.04 are being addressed by MLB through the method modification process. Compared to the presence/absence outcome associated with qualitative methods, quantitative methods such as AOAC Method 2008.05 (Three-Step Method) provide a conventional, quantitative measure of efficacy - log reduction. In 2008, MLB's research led to an official validation of the Three Step Method (TSM) for liquids on hard nonporous surfaces by AOAC. In 2009, the TSM was officially modified to include porous coupons. MLB will use specific SAP recommendations to establish research priorities for the B. anthracis work. Surrogate microbes for both spore formers and vegetative bacteria are a fundamental aspect of testing the performance of antimicrobial products, and the use of safe-to- handle surrogates for efficacy testing of bio-threat agents is supported by the EPA. The selection and testing of coupon materials, porous and non-porous, relevant to environmental surfaces are important initiatives associated with this research program. Ultimately, the data and study conclusions will be used to develop/supplement regulatory guidelines for antimicrobials and decontamination products to be used in the treatment of buildings and environmental surfaces. Homeland Security projects consist of procedural modifications to methods, validation of new methods, and comparative testing of methods. An annual work plan will be developed as projects are completed and others are initiated. Timelines and deliverables associated with MLB work plan, Interagency Agreement (IA) and contracts will form the basis for research priorities and project management. Single and multi-laboratory validation trials are necessary to demonstrate repeatability, reproducibility, technical soundness, and to verify that the data supports the applicability of the method. Collaborators, namely those under contract and lAs, assist EPA with this effort. Volunteer laboratories may also participate in this project. Agency priorities and guidance from the Antimicrobials Division of OPP will be considered as the program is implemented and new projects are developed. Through funding provided by OCSPP, a multi-tiered research plan has been developed and initiated. An Interagency Agreement (IA) has been established with (the U.S. Army's Edgewood Chemical Biological Center (ECBC) to assist EPA in this effort. In part, the work associated with this IA will build on accomplishments achieved under the previous IA, especially the laboratory testing of virulent biological warfare agents (BWAs). The scope of this IA includes the preparation of manuscripts for publication, evaluation of quantitative efficacy test methods for antimicrobial chemicals and to provide the data and study conclusions to the EPA necessary to establish regulatory decisions for products to be used in the treatment of environmental surfaces contaminated with virulent B. anthracis and vegetative BWAs such as Francisella, Yersinia and Brucella. ECBC will carry out a series of studies designed to expand the scope of current test methodologies such as the Three Step Method, to improve the quality and consistency of the efficacy data, and to evaluate disinfectants against vegetative BWAs. Projects may consist of procedural modifications to methods, pre-validation studies on new methods, and side-by-side comparative testing. Single and multi-lab oratory validation trials may be necessary to demonstrate repeatability, reproducibility, technical soundness, and to verify that the data supports the applicability of the method. ------- BEAD/MLB July 2011 Page 8 of 38 AOAC INTERNATIONAL (AOAC) has been contracted to assist EPA with the procedural, technical, analytical, and statistical peer review for acceptance of study design protocols and associated data, and the publication of validated methods for determining disinfectant efficacy, particularly for bioterrorism agents. AOAC will provide the necessary expertise, through committees and appropriate advisory panels, to review and approve validation and collaborative study protocols. AOAC will publish methods and related information. MLB has published two papers on the development and validation of quantitative test methods for sporicidal decontaminants, including research on surrogates and coupon materials: 1) Tomasino et al., JAOAC, Vol. 91, No.4, 2008 (Determining the Efficacy of Liquid Sporicides against Spores of Bacillus subtilis on a Hard Nonporous Surface Using the Quantitative Three Step Method), and 2) Tomasino et al., JAOAC, Vol. 93, No. 1, 2010 (Use of Alternative Carrier Materials in AOAC Official Method 2008.05). Additional projects will build upon these efforts. MLB is interested in the evaluation of additional standardized porous materials (e.g., HTR, a polymer based substance) and their utility in the quantitative Three Step Method. In addition, the EPA Office of Emergency Management (OEM) approached the laboratory in the summer of 2010, to provide laboratory services to evaluate a Rapid Viability Polymerase Chain Reaction (RV-PCR) method initially developed by Lawrence Livermore Laboratory (LLNL) for EPA as a research method for detection of Bacillus anthracis in environmental samples. OEM provided equipment, supplies, and materials for the method. Two scientists from MLB spent two weeks on site at LLNL training on the method. The Phase I of the Bio-Response Operational Testing and Evaluation (BOTE), an interagency project, was conducted during April-May 2011 to evaluate field-level facility biological remediation studies of various decontamination technologies. The tests were performed using intentional release (aerosolization) of spores of Bacillus atrophaeus subspecies globigii (BG), a surrogate for Bacillus anthracis, the microbial agent for anthrax. Three decontamination methods, namely, fumigation with vaporized hydrogen peroxide (VHP), fumigation with chlorine dioxide (C1O2), and a treatment process including the use of pH-adjusted bleach, were assessed with in-between re-setting and re-staging of the facility. Sixty-two wipe samples including the field and positive and negative controls were processed for evaluation under BOTE exercise. The method uses processing steps to 1) recovery of spores from wipes 2) collection of spores by filtration, and 3) incubation of spores for viability and multiplication is followed by subsequent DNA extraction and real-time PCR analysis. The RV-PCR method uses PCR analysis, pre- and post-incubation, and exploits the change in the PCR cycle threshold (Ct) value as an indicator for the presence of viable spores or cells. The approach referred to as "rapid viability" (RV). For all field samples, field blank samples, and laboratory positive and negative control samples for all three events (pre- and post-decon), both culture and RV-PCR data were recorded. Evaluation of the method led to suggested modifications to the method with particular attention to the DNA extraction technique (e.g., incorporation of heat-mediated lysis for DNA extraction) and evaluation of interferences in TO samples (e.g., dilution of TO samples). A second exercise (Phase II) is anticipated with updated RV-PCR protocol in September 2011. IV. Center for Disease Control and Prevention (CDC) Select Agent Laboratory ------- BEAD/MLB July 2011 Page 9 of 38 The OPP Microbiology Laboratory has registered and been granted a certificate under the CDC Select Agent Rule (Public Health Security and Bioterrorism Preparedness and Response Act of 2002). The laboratory wing includes Biosafety Level 3 laboratories which enable the laboratory to provide critical laboratory capacity in the event of a bio-threat event. The laboratory is part of the Environmental Laboratory Response Network (ELRN) which is a nationwide laboratory network which is available to provide capabilities and capacity during an environmental event. The ELRN is coordinated by the EPA. The registration certificate extends to June 2014; CDC may audit the laboratory at any time to determine continued compliance with requirements of the Select Agent Rule (42 CFR Part 73). Nine individuals have approved Security Risk Assessment from the Federal Bureau of Investigation to work with the select agent. V. Biofilm MLB has initiated a Biofilm Research Program to develop and evaluate efficacy test methods for growing and treating bacteria in biofilms, and to provide the data, analyses, and study conclusions necessary to support/establish regulatory guidelines for products with claims to treat environmental surfaces colonized by biofilm. When necessary, research priorities will be formed jointly in conjunction with the Antimicrobials Division. The laboratory submitted a one- step biofilm efficacy test method to ASTM in April 2011 for consideration as a standard method. The development of performance standards (log reduction of biofilm) and acceptable label claims will be determined as the research proceeds. VI. Virucidal testing Program A primary focus of MLB is the efficacy evaluation of antimicrobial products (used to kill or suppress the growth of infectious microorganisms on inanimate objects and surfaces) with public health claims that are registered by the EPA. Applied research on the evaluation and development of methods used to determine the efficacy of antimicrobials is a key priority. The laboratory has traditionally focused on bacteria. Given issues with viral gastrointestinal illness, avian influenza, and preparedness issues associated with pandemic influenza, the laboratory has expanded its services to test viruses and their appropriate surrogates as the microbial agents for virucidal claims. The Virucidal Testing Program (VTP) will focus on the testing of disinfectants against viruses. The program is currently on hold due to other pressing priorities. Additional Functions 1. Operate a pre-regi strati on testing program to verify selective antimicrobial efficacy claims and assure the quality and integrity of registrant-submitted data. 2. Serve as a source of technical information regarding test methodology to referee disputes, and confirm test sample results from state government laboratories. ------- BEAD/MLB July 2011 Page 10 of 38 3. Provide technical and training support to state laboratories. 4. Carry out development of new antimicrobial test methods, including the evaluation of potential screening or rapid methods. 5. Participate in collaborative ("round robin") efficacy testing of new test methods for evaluating antimicrobial products. 6. Participate in data audits and GLP inspections of commercial/industrial labs which conduct efficacy testing of disinfectants and antimicrobial devices. 7. Serve as expert witness in Agency conducted hearings. The client base includes the Antimicrobials Division (AD), the Biopesticides and Pollution Prevention Division (BPPD), the EPA Office of Emergency Management (OEM), and the EPA Office of Research and Development (ORD) as well as other government and state Agencies. Core program work is conducted in consultation with the client. Review and signature of the study protocols is at the client level. B. MANAGEMENT AND ORGANIZATION I. General Organizational Structure The general organization structure of the Office of Pesticide Programs and Biological and Economic Analysis Division is included in Appendices A-l and A-2. MLB is one of three laboratories providing laboratory, technical, and scientific support to the Office of Pesticide Programs. The laboratory's general organizational structure is outlined in the appendix. The Branch Chief of the Microbiology Laboratory Branch is considered top management for the purposes of implementation of the principles of the QMP. The Branch Chief has overall responsibility for management of the work, personnel, resources, and administrative and programmatic functions for the Branch. The Branch Chief reports to the Director of the Biological and Economic Analysis Division (BEAD). The laboratory Senior Science Advisor and the Team Leader report directly to the Branch Chief on technical, work planning, and administrative issues. The Senior Science Advisor or Team Leader may act for the Branch Chief during absences from the office. Depending on the program (Antimicrobial Testing, Homeland Security, R & D) the staff report to the Team Leader (TL) or senior science advisor (SSA) on technical issues. The TL or SSA will report to the Branch Chief on progress of the laboratory studies toward meeting the goals established in the annual workplan. The SSA directs and administers laboratory programs related to extramurally funded Homeland Security initiatives, core program antimicrobial testing, research on the OECD and other quantitative test methods, and oversight on contract deliverables. The TL provides oversight for , BOTE project, general laboratory quality control procedures, and selected R & D projects (C. difficile in particular). ------- BEAD/MLB July 2011 Page 11 of 38 The Laboratory's Quality Assurance Unit (QAU) has primary quality assurance oversight and operates independent of the analysts and management team. See section on "responsibilities" for more detail on the responsibilities of the QAU. The QAU reports directly to the laboratory Branch Chief. II. Mission The mission of the program office is the regulation and oversight of pesticide products. The overarching theme of work underway at the laboratory is to provide microbiological laboratory support to the Office of Pesticide Programs. The focus of the programs at the laboratory change as OPP's needs change. In recent years, the focus has been on the efficacy evaluation of antimicrobials, efficacy method development and modifications, research related to the ATP methods, PCR based method for anthrax detection, and development of methods for novel product types (towelettes) and emerging pathogens (for example, Clostridium difficile). Mission program support for the efficacy and formulation evaluations of tuberculocides and hospital disinfectants is also provided by three state laboratories. The laboratory uses extramural agreements (contract, lAGs, grants) to facilitate the development of data necessary to meet the Program goals. III. Policy on Quality Assurance The goal of the Agency-wide Quality System is to ensure that environmental programs and decisions are supported by data of the type and quality needed and expected for their intended use. On February 23, 2004, the Agency's Science Policy Council issued a new Agency Policy Directive, Assuring the Competency of Environmental Protection Agency Laboratories. To assure the quality of data generated by our laboratories, all the laboratories operated by EPA need to maintain a documented Quality System that at a minimum complies with the requirements of the EPA Quality System as defined by EPA CIO 2105.0 May 2000, EPA Quality Manual for Environmental Programs. Where appropriate accreditation programs are available for one or more components of a given laboratory's operations, the laboratory will seek accreditation for those components. Consistent with this policy, MLB is GLP compliant and ISO 17025 compliant for selected methods as defined in the laboratory's scope of accreditation for testing under the Antimicrobial Testing Program. The laboratory accreditation body is A2LA. The objectives of the Good Laboratory Practices (GLP) program, ISO 17025 accreditation, the overarching quality assurance (QA) program, and quality control (QC) checks are to ensure the validity and accuracy of the data. The laboratory follows the prescribed laboratory practices identified in the Good Laboratory Practice Standards (40 CFR Part 160) and has been audited and found to be GLP compliant. The management fully supports a robust Quality Assurance Program and has allocated resources to support a Quality Assurance Unit required to ensure a strong and active program. In addition, the management is committed to meeting the requirements of the ISO 17025 standards for methods within the scope of the ------- BEAD/MLB July 2011 Page 12 of 38 accreditation. The laboratory continually strives to improve the effectiveness of the quality systems and seeks feedback from the laboratory clients on a regular basis. The QMP provides the overall framework for the laboratory's Quality Assurance Program. Quality Assurance Project Plans support the key program areas; the Antimicrobial Testing Program, the Plant Incorporated Protectant method validation program, and the Homeland Security initiatives. Standard Operating Procedures (SOPs) form the basis for work at the laboratory and are numbered by program element (microbiological methods, quality control, equipment, quality assurance, chain of custody and administrative). Study protocols which provide the detail for each independent study are developed and reviewed and approved by the client organizations. A schedule is followed for review and revision of the SOPs. As required by GLPs, an audit schedule is developed each year which includes internal technical system audits, books and records audits, and audits of individual studies. The laboratory is also subject to external technical and management systems audits which serve to identify any deficiencies in the overarching quality assurance program. External audits are also conducted to ensure compliance with Good Laboratory Practices and ISO 17025 requirements. Deficiencies are addressed as necessary though a corrective action process. The Branch Chief and QAU are committed to meeting the necessary quality assurance requirements and compliance or accreditation standards for the organization. The laboratory is compliant with the Good Laboratory Practice Standards (GLPs) and has been audited on a regular basis against this standard. Once accreditation under ISO 17025 is achieved, the laboratory will comply with the International Standard for the methods under the scope of accreditation and will continually work to improve the effectiveness of the management system. The coordination for ISO 17025 accreditation for the OPP laboratories is managed out of the BEAD Immediate Office (IO) and support is provided via a workgroup consisting of laboratory management and the Quality Assurance Units from each of the laboratories. The senior management is fully committed to adhering to the ISO 17025 requirements and working to continually improve the laboratory's quality system. IV. Responsibilities The Laboratory Competency Policy Directive mandates that the laboratory operate in conformance with the Agency's Quality Policy and seek accreditation where applicable. The laboratory accomplishes this by adherence to the Good Laboratory Practice Standards and by following the ISO 17025 standard for testing and calibration laboratories. The laboratory utilizes a prescribed quality assurance program with thorough documentation of all quality control activities. Senior management is responsible for allocating resources and support to the Quality Assurance Officer (QAO) as necessary to implement the recommended quality assurance activities of the laboratory. The Branch Chief is responsible for ensuring that corrective actions/preventive actions are taken to address deficiencies noted during audits of laboratory data and to prevent such deficiencies. All staff involved in conducting laboratory assessments is responsible for ensuring that required quality control measures are carried out as prescribed in the SOPs. Laboratory staff are ------- BEAD/MLB July 2011 Page 13 of 38 responsible for the intra-laboratory review of data generated under the program. The laboratory has an assigned Quality Assurance Officer (QAO) and an alternate QAO. The two person team is designated as the Quality Assurance Unit (QAU). The QAO has primary responsibility for Quality Assurance activities; the alternate provides support when the QAO is not available or as the laboratory workload warrants. The QAU operates independently of the laboratory management team and is free to conduct audits, review books and records, evaluate analyst capabilities, develop and implement proficiency programs, and evaluate training needs as they relate to Quality Assurance. The QAU works closely with the laboratory management team (Branch Chief, Team Leader, and Senior Science Advisor) to address issues and concerns about the day to day operations and activities of the laboratory. The QAU reports to the Laboratory Branch Chief on areas of responsibility. The QAU coordinates the process of documenting, investigating, and follow-up on non-conformances and corrective action plans for studies using methods listed under the laboratory's scope of accreditation under ISO 17025. In addition, the Quality Assurance Officers can approach the Director of the Biological and Economic Analysis Division or the OPP Director of Quality Assurance to address concerns, discuss outcomes, and provide support for improvements to the Quality Systems. If QA related issues cannot be resolved between the QAU and Branch Chief, the QAU can report directly to the Division Director or Associate Director. The appointed QAU for the laboratory is responsible for determining whether all SOPs, QA/QC, and GLP and ISO-17025 requirements are met. The QAU reviews the quality of data and study reports, conducts on-site planned audits, and makes unscheduled visits for observations to assess whether the testing and general laboratory operations are carried out in accordance with approved SOPs. The QAU maintains the master schedule of testing activities and works in cooperation with the Team Leader/senior science advisor to prepare an annual audit schedule. The QAU maintains files of master copies of all SOPs, master schedules of testing activities, audit schedules, records of audits and responses, non-conformance reports, and records related to corrective and preventive actions. In conjunction with the Branch Chief and Associate Director, the QAU operates to ensure that the laboratory meets the specifications, goals, and objectives of the Quality Management Plan (QMP). The QAU reports directly to the MLB Branch Chief on administrative or technical matters. The Senior Science Advisor (SSA) and the Team Leader (TL) report directly to the Branch Chief. Managerial authority is delegated first to the Senior Scientist, then Team Leader, or senior ranking microbiologist as necessary during Branch Chiefs absence. The Team Leader is responsible for the coordination of core testing activities and support of analysts in the Laboratory. In addition, technical oversight of the laboratory programs is provided by the Senior Science Advisor. The SSA provides technical and scientific advice to the laboratory in all program areas and has responsibility for leading scientific initiatives to enhance, augment, or develop laboratory's capabilities to support ongoing regulatory and Homeland Security initiatives. The SSA provides expert advice, counsel, and leadership on laboratory studies, ------- BEAD/MLB July 2011 Page 14 of 38 contractual, and research needs. The QAU also has access and a line of communication to the OPP Director of Quality Assurance (DQA). The DQA provides guidance to the QAU on quality assurance practices and procedures, audit schedules, training, and other activities. The OPP DQA provides support for internal and external audits, review of Quality Management Plans, and gives advice on quality assurance related issues. The OPP DQA is responsible for final approval of the Quality Management Plan, and conducts annual Management System Reviews (MSRs) to ensure that QA activities are carried out according to the QA Management Plan and deficiencies identified during management system reviews are adequately addressed by the laboratory. Quality Assurance Project Plans (QAPPs) for new program areas are developed as needed and are approved by the QAO or alternate. The type of plan will be dependent upon the work to be performed. Refer to the Appendix for the list of the QAPPs currently in place. Each year, the QAO is also responsible for preparing the laboratory's contribution to OPP's Quality Assurance Annual Report and Work Plan (QAARWP). For Homeland Security projects, the Senior Science Advisor serves as the Principal Investigator (PI) and has the overall responsibility for the technical conduct of the projects. Quality assurance issues are addressed in the laboratory through consultation of the QAO with the Team Leader, Senior Science Advisor and Branch Chief. Issues not amenable to resolution at this level are resolved between the Associate Director and Branch Chief. If resolution cannot be achieved, the matter is raised to the Division Director. On issues of a complex nature, the management team may consult with the OPP DQA. The Laboratory generates enforcement sensitive data. Access to this data is limited to internal EPA personnel within the Antimicrobials Division and the Office of Regulatory Enforcement. Development of testing protocols for these studies may require access to Confidential Business Information (CBI) submitted by the antimicrobial product registrant under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Access to FIFRA CBI is given only to Federal, contract and NOWCC employees who need the information in the conduct of official Government Business and only after certain requirements have been met. The requirements include a FIFRA security briefing, review of the FIFRA security manual, approval from the division director, and completion of the FIFRA Access Authorization Agreement. Training and renewal of access authorization is required on an annual basis. All EPA employees are required to be familiar with the government-wide ethics regulations and the EPA supplemental ethics regulations which include rules for EPA employees regarding prohibited financial interests and outside employment. The Standards of Ethical Conduct for Employees of the Executive Branch are defined in 5 Code of Federal Regulations (CFR) Part 2635. In addition, the EPA has defined the general principles of public service and each employee is required to take annual ethics training. V. Resource Allocation ------- BEAD/MLB July 2011 Page 15 of 38 Resources for the implementation of quality assurance practices in the laboratory are allocated on an annual basis. The laboratory has assigned a QAO and an alternate QAO, collectively known at the Quality Assurance Unit (QAU). The QAU attends Agency quality assurance training as well as other training provided by private entities. Other staff and analysts are also trained as the need arises and adequate resources are available. Traveling and training funds are set aside for this purpose on an annual basis. Capital investments are made to improve the quality assurance aspects of the laboratory program. If extramural resources are required, suppliers and contractors must meet the appropriate quality control and assurance requirements as identified in the Agency's quality assurance guidelines. Equipment calibration and certification by ISO 17025 accredited vendors is an integral part of the QA program. In consultation with the staff and upon general direction from the client organizations, the laboratory develops an annual workplan which identifies the project, estimated quarter(s) in which the work will be performed, the outputs/deliverables, estimated completion date, the assigned analyst, and the estimated resource allocation to a 10* of an Full Time Equivalent (FTE). An FTE is defined as approximately 2080 hours of work per year. The workplan is shared with the client organizations. The Division Director is responsible for negotiating any changes to the workplan with the client organizations. Changes to the workplan may be made throughout the year if necessary to support program initiatives. Laboratory initiatives fall under the Agency's Goal 4; Healthy Communities and Ecosystems. Work is assigned to individuals or small teams. Status meetings are held on a regular basis in order for the analyst/teams to provide updates to the Branch Chief and senior staff on the progress toward meeting the goals in the workplan, to address technical or resource issues, to review the data and findings, and to plot next steps. The QAU is involved in the technical and workplan discussions. The importance of meeting customers' needs is stressed. The client organizations are involved in the work planning process and concur on study protocols and process related SOPs. The annual workplan is revisited throughout the year with the staff, as well as senior management (Division Director and associate) and the client organizations. Adjustments are made as necessary based on feedback from the various organizations and management levels. Performance objectives and the importance of the assigned work are shared with the analysts throughout the year. Performance goals for each individual are established in annual performance plans through the Agency's performance system (PARs). The goals are established by management and the individual and are reviewed periodically throughout the year. A mid- year and end of the year performance review with each employee is required. C. QUALITY SYSTEM AND DESCRIPTION I. Principal Components The Agency's policy and program requirements to implement the mandatory QA ------- BEAD/MLB July 2011 Page 16 of 38 programs are contained in EPA CIO 2105.0. As stated in EPA CIO 2105.0, "the primary goal of the QA program is to ensure that all environmentally related measurements supported by the EPA produce data of known and acceptable quality." The quality of data is known when "all components associated with its derivation are thoroughly documented, such documentation being verifiable and defensible." As of October 16, 1989, the Agency requires that efficacy studies performed by registered laboratories in support of submissions under FIFRA be conducted in compliance with Good Laboratory Practice (GLP) regulations. The laboratory is charged with verification of efficacy claims of hospital disinfectants, including products which also make tuberculocidal claims. As enforcement actions may be taken based on the efficacy data generated by the laboratory, it is committed to producing data of known, acceptable, traceable, and defensible quality. In addition, data generated in other program areas is used to make recommendations which affect the regulation of pesticides, particularly antimicrobials and plant incorporated protectants (PIPs). The laboratory operates in conformance with GLPs and with a quality system in place with thorough documentation of all quality control measures to support the testing program. The laboratory also follows the ISO 17025 standard for methods defined under the laboratory's scope of accreditation. The principal components of the laboratory's quality system are the Quality Assurance Management Plan, the Agency's Good Laboratory Practice Standards, ISO 17025 (for selected efficacy test methods), Standard Operating Procedures, Quality Assurance Projects Plans, and Study Protocols. Essential quality control measures are integrated into the SOPs which form the basis of laboratory operations. The SOPs are reviewed at least once every three years, and are revised as necessary. This promotes continual improvement of the SOPs and assessment of the adequacy of quality control requirements. The basic structure of the document system is as follows: Quality Management Plan (QMP) - establishes the overarching principles of the quality system in the laboratory. All Agency organizational units governed by EPA CIO 2105.0, CHG 2 shall document their quality system in a Quality Management Plan (QMP). The QMP is a policy statement describing how an EPA organization shall comply with the requirements of EPA CIO 2105.0 CHG 2. Quality systems encompass the management and technical activities necessary to plan, implement, and assess the effectiveness of QA and QC operations applied to environmental programs. Quality Assurance Project Plan. EPA policy requires that all work performed by or on behalf of EPA involving the collection of environmental data shall be implemented in accordance with an Agency-approved Quality Assurance Project Plan (QAPP). The QAPP defines and documents how specific data collection activities shall be planned, implemented, and assessed during a particular project. Guidance on developing QAPPs, including examples of QAPP elements, may be found in Guidance on Quality Assurance Project Plans (QA/G-5) (EPA 1998). The QAPP is a critical planning document for any environmental data operation since it documents how environmental data operations are ------- BEAD/MLB July 2011 Page 17 of 38 planned, implemented, documented, and assessed during the life cycle of a program, project, or task. The planning includes the "stakeholders" (i.e., the data users, data producers, decision makers, etc.) to ensure that all needs are defined adequately at the outset and that the planning for quality addresses the specific needs defined. The laboratory has five Quality Assurance Project Plans currently in place; 1) QAPP for the Antimicrobial Testing Program; 2) QAPP for the Plant Incorporated Protectant Method Validation Program; 3) QAPP for Homeland Security research initiatives, 4) QAPP for Biofilm and 5) QAPP for Virology Testing Program. Quality Assurance Project Plans are required for all extramural projects as part of the contract and TAG planning process. Standard Operating Procedures (SOPs). A Standard Operating Procedure is a document which provides step-by-step description of how a specific operation, method, or procedure is performed. The laboratory has SOPs for administrative, chain of custody, quality control, equipment calibration and maintenance, microbiology, special programs (PIP, Biofilm and Virology) and quality assurance procedures. An index of the SOPs is an attachment to the QMP. Study Protocols - The laboratory develops study protocols for all antimicrobial testing program (ATP) studies, research studies and other unique laboratory studies. The protocols provide the detail necessary to recreate the study. Collectively, these documents provide the structure and framework for documenting the laboratory practices and procedures. Other documents necessary to support the laboratory programs including laboratory audits, books and records inspections, logbooks, notebooks, and data recording sheets complement the documents noted above. II. Process Development of Documentation Documents are developed to provide guidance, instruction, operating procedures, and structure to the laboratory program. Overarching principles of the laboratory's Quality System are identified in the Quality Management Plan (QMP). Standard Operating Procedures (SOPs) establish the framework for operational principles and detailed guidance for test methods, equipment calibration and maintenance, preparation of media and reagents, data recording, records maintenance, and preparation of reports. For each overarching laboratory program, a Quality Assurance Project Plan (QAPP) is developed. The laboratory has QAPPs for the Antimicrobial Testing Program, the Plant Incorporated Protectant method validation program, the virology program, and Homeland Security research initiatives. Under each QAPP, study protocols are developed which provide the detail and outline for conducting a particular laboratory study. Collectively, these documents provide the framework for the laboratory programs. All documents are developed collaboratively with the client organizations and staff. All documents are reviewed by the QAU prior to final signoff and approval by the Branch Chief. Client organizations provide feedback on study ------- BEAD/MLB July 2011 Page 18 of 38 design and protocols. Substantive changes to study protocols are reviewed with the client and approval documentation is included in the study folder, notebook, or binder. The client serves as the study sponsor for the purposes of the study protocol. Once the study design and protocol or approach is approved, the study is conducted and the data is tabulated using standard forms or in a laboratory notebook. SOPs provide guidance for how to capture the data. Periodic audits, peer review of the data, and review of logbooks and records are conducted. Peer Review and Audit Reports The peer review and QAU review of all raw data and all final reports ensure that the quality control requirements are being met. Regular audits of general laboratory operations and performance of testing methods are also essential parts of the Laboratory's quality system. The QAO is responsible for conducting internal audits to determine whether SOPs are being used and followed correctly. The QAO also makes unannounced visits to observe laboratory operations. These ongoing activities provide for continual assessment of the effectiveness of quality control procedures. Audit reports are submitted by the QAO to the Team Leader, Senior Science Advisor and Branch Chief and the analysts within the specified timeframe for completion of the audit. Responses must be returned to the QAO and Branch Chief within an agreed upon timeframe. The Team Leader in consultation with the analysts is responsible for addressing each finding or observation. A reason for the non-conformance, as well as a plan for corrective action, is required. If the QAO finds the corrective action deficient, the situation is discussed with the QA Manager for the Office of Pesticide Programs, the Team Leader and the Branch Chief. These procedures are detailed in Laboratory SOP QA-01, Quality Assurance Unit and its Functions. The corrective actions are documented and filed in a central location. Follow up is conducted to determine if the corrective action has the desired effect. The QAU meets with the Branch Chief to discuss the corrective action plans and to review process improvements. Handling of Non-Conformance Issues If it is determined that the laboratory has a non-conformance issue or there is a required corrective action, the QAU will initiate the action following the procedures noted in Standard Operating Procedure, ADM-07 (Non-conformance reports) and ADM-08 (Corrective and Preventive Actions. The analysts, Branch Chief, Team Leader, and Senior Science Advisor are involved in the process of identifying non-conformances, evaluating the root cause of the non-conformance, and addressing any corrective or preventive actions, if necessary. The Quality Assurance Officer in consultation with the senior team is responsible for determining the actions necessary to address the non-conformance issue and notifying the client if the finding affects the outcome of a study. The corrective action will include the steps necessary to avoid recurrence of the non-conformance. If it is necessary to develop data to address a ------- BEAD/MLB July 2011 Page 19 of 38 scientific issue related to a non-conformance, the Team Leader or Senior Scientist will initiate the development of a study protocol. All corrective actions including the action plan and data summary are tabulated in a binder which is maintained by the QAU. If the non-conformance issue occurs during the conduct of a study and is determined to affect the outcome of the study, the study may be terminated in accordance with the standard procedures. The Branch Chief is notified of the findings and will make a decision as to whether to terminate the study. A termination memo will be issued which documents the reason for termination of the study, the plan to address the non-conformance, and the plan for re-initiating the study. The termination memo will be filed with the study and included in the corrective action binder. The client will be notified and the study will be re-initiated when the issue is resolved. Preventive Actions On an ongoing basis, the QAU will review the corrective actions and determine if non- conformance issues are recurring or onetime events. For recurring events, the QAU will recommend to the Branch Chief a plan for resolving or rectifying the problems. Continuous improvement of the laboratory's procedures and systems for conducting work is critical to the integrity and quality of the data and is a major theme of ISO 17025. Extramural Agreements The laboratory has established numerous extramural contracts and Interagency Agreements (lAGs) in order to support the Homeland Security research objectives. The Agency's contracting regulations require that data is developed in accordance with the Agency's Data Quality Objectives and Quality Assurance requirements. Quality Assurance requirements are built in to Requests for Proposals (RFPs) and Technical Evaluation Criteria. The preparedness of each participating laboratory, including the OPP Microbiology Laboratory, is assessed by the MLB Senior Science Advisor (or designee) and Quality Assurance Unit (QAU) prior to initiation of the study to ensure compliance with the Quality Assurance Project Plan and associated study protocol. Readiness reviews are conducted in advance of the initiation of research. The expected level of quality assurance for organizations operating under extramural agreements with the laboratory is consistent with EPA Good Laboratory Practices. Numerous guidance documents, standard methods and SOPs are used to maintain data quality. Proper record keeping and archiving are performed to ensure the defensibility and re-constructability or reanalysis of the study. The client was consulted to determine if ISO 17025 or Good Laboratory Practices were required for data developed by the three state laboratories to support the activities of the Antimicrobial Testing Program. The client requested adherence to the Good Laboratory Practice (GLPs) standards. Staff performing the assays must be familiar with standard microbiological techniques such as aseptic transfer, serial dilutions, plate counts and microbe identification. Scientists ------- BEAD/MLB July 2011 Page 20 of 3 8 and analysts involved in testing shall be familiar with each efficacy method and associated procedure (e.g., carrier counts, neutralization confirmation) and will be proficient in conducting each designated efficacy test method. In-house practice sessions are required for each laboratory to build proficiency with each method prior to official testing. Documentation of practice and training for projects is maintained in a training file. Where possible, EPA SOPs and standard forms are used for those operations which have become or will become routine, including test methodology, analytical procedures and calibration procedures. SOPs that are comparable to EPA's may be used; however, their use requires concurrence by the Senior Scientist (or designee) or the EPA Quality Assurance Unit. Electronic spreadsheets and email are considered official documentation and will be maintained and archived accordingly. Test chemicals, media and reagents are tracked using assigned media preparation numbers. No official chain of custody documentation is required for test chemicals evaluated in Homeland Security research; however, specific information on source, identification, and volume received is maintained and archived. Upon completion of each study, a peer review of the data entry/tabulation is performed by laboratory personnel. A draft report of the findings or data summary is compiled and forwarded to each lab's Quality Assurance personnel for review. The designated QAO at each facility will review and comment on the data and supporting information before submission to the statistician. Data may be rejected if microbial contamination occurs at a level unacceptable to MLB. Client Communication The Microbiology Laboratory communicates with the client organizations on a regular basis. The current client base is the Antimicrobials Division, the Biopesticides and Pollution Prevention Division, the Office of Enforcement and Compliance Division, the Office of Research and Development, the Office of Emergency Management, as well as administrative, technical and programmatic support from the program office and contracts office. The laboratory holds regular meetings with the Branch Chief of Product Science Branch of Antimicrobial Division. The client has agreed that for the purposes of efficacy testing under the Antimicrobial Testing Program (ATP) that the laboratory data that is generated must be in compliance with Good Laboratory Practice Standards, 40 CFR Part 160. The design and conduct of laboratory studies is done with the client organization with final signatures by both parties. Amendments to the studies are done as necessary and with the approval of the client. Data may be presented both orally and in written format. Formal technical reports or summaries of data are delivered to the client. If certain parameters of the study do not fall within the prescribed requirements (for example, the carrier counts for a study fall outside the established range) the client is contacted. The study may be repeated as requested by the client. Conversations are documented and maintained with the study file. Customer complaints (SOP ADM-06) and resulting corrective actions (SOP ADM-08) are handled as outlined in the appropriate Standard Operating Procedures. ------- BEAD/MLB July 2011 Page 21 of 38 D. PERSONNEL QUALIFICATIONS AND TRAINING I. Policy The Agency encourages the continued training, certification, and professional development of the laboratory staff to meet program objectives. Resources are allocated for these activities on a continuing basis. Training is obtained through formal academic training, equipment specific training provided by the vendor, formal in-house refresher training on microbiological techniques and methods, and project specific training on standard methods. Documentation of training is maintained in a binder as specified in the laboratory training SOP, ADM-04. II. Qualifications and Training The work performed at the laboratory consists of microbiological and chemical assays. Analysts are required to use standard laboratory equipment, as well as new technology specific to the mission of the program. Analysts must meet the minimum qualifications set forth in Handbook 118 for microbiologists, or for biologists with a minimum of 20 semester hours in microbiology and related studies. Personnel job applications, curricula vitae, etc. are maintained by the Branch Chief. Job descriptions and training records for each employee, as specified under the GLPs Section 160.29(b), are maintained in the laboratory training binder and are available for inspection. Student assistants and interns are required to have basic microbiology and chemistry courses at the college level. On-the-job training will be provided to each student by senior laboratory personnel on laboratory specific practices and procedures. Students may work independently on assigned research projects with direction and guidance from the laboratory Team Leader or Senior Science Advisor. All laboratory staff is required to have 24 credits of general laboratory safety training as specified under the Agency guidelines. A refresher class of 8 credits is required on an annual basis. If specific personal protective equipment such as respirator is required, the analyst must be certified. The laboratory staff is trained in the laboratory operations through review of SOPS, QA/QC requirements, chain-of-custody procedures, and record keeping requirements. New staff members receive extensive hands-on training from the Team Leader or senior analysts on methods and procedures used in the laboratory. Staff obtains experience by performing practice trials including handling of cultures, disinfectants, chemicals, etc. The Quality Assurance Officer provides training on various aspects of quality control procedures. Methods related to safety and health practices are also covered by the ESC Industrial Hygienist and the facility safety officer. Training by the vendors of specialized microbiology laboratory equipment (e.g. confocal microscope, Vitek 2 Compact Identification system for microorganisms) is ------- BEAD/MLB July 2011 Page 22 of 3 8 conducted as needed. QA training is recorded in the training file for each employee. For professional development, analysts are encouraged to attend seminars and professional meetings such as those of the American Society for Microbiology (ASM), Association of Official Analytical Chemists (AOAC) International, Association of Practitioners for Infection Control (APIC) and Analytical Excellence through Industry Collaboration (AEIC), etc. Information on new equipment is obtained through trade journals, trade shows, and vendor demonstrations. Specific training needs related to successful performance of laboratory duties, available through AOAC International, the National Institutes of Health (NIH), the US Food and Drug Administration, state laboratories, or other organizations, may be identified and submitted as training requests. Funding for training is allocated during the annual budget planning process. The Agency, through its Office of Environmental Information Quality Staff, provides basic training courses in quality assurance for Quality Assurance Officers. BEAD management supports the QA program by providing funding for training and travel. BEAD allocates funding for the QAO to participate in EPA's annual QA conferences. III. Proficiency Testing/Uncertainty In order to reduce potential variability in results and to assess the performance of analysts in conducting pertinent laboratory functions, MLB is currently developing a proficiency testing program for methods used for efficacy testing under the Antimicrobial Testing Program. AOAC International has been tasked (under a contract) with facilitating the development of the program. Operations (modules) that are expected to be evaluated include basic microbiology laboratory tasks such as use of pH meters, weigh balances, and spectrophotometers, and performing product efficacy tests. The proficiency testing program will be used to identify training needs and SOP deficiencies. The Team Leader, in conjunction with the Senior Science Advisor, is responsible for implementing the program and evaluating the results. Assistance from the QAO will be provided as necessary to ensure the quality of data. Refer to the "OPP Microbiology Laboratory Response to the EPA Laboratory Competency Policy Directive, Implementation Plan", Reference #5. For the PIP method validation program, the laboratory participates in the USDA Grain Inspection, Stockyards and Packers Administration (GIPSA) proficiency program for the detection of biotechnology events. Blind samples are sent to the laboratory for screening. The laboratory returns the data to GIPSA for analysis, and the results are posted for each laboratory. The PIP method validation program has been static for several years. Method validation work under this program is not anticipated within the next fiscal year. For the Homeland Security research, quality assurance readiness reviews and in-house practice sessions are used to develop and monitor proficiency in conducting microbiological techniques associated with test methods prior to the initiation of the research. ------- BEAD/MLB July 2011 Page 23 of 3 8 MLB recognizes the importance of uncertainty of measurement, or error, associated with the lab's activities. Where possible, certified media and reagents and specialized equipment (e.g., specific types and sizes of pipettes, volumetric glassware) are used in the laboratory's assays. Rigorous quality assurance, staff training, and calibration of equipment such as balances, pH meters and spectrophotometers are used to increase reproducibility of data. Equipment for quantitative assays such as positive displacement pipettes and cuvettes are performance tested and validated by the manufacturer. Quantitative efficacy tests are replicated by the laboratory to provide within-lab standard deviation values, or when necessary, are performed by more than one laboratory to provide between-lab standard deviation values. The laboratory utilizes AOAC- validated methods for the ATP program and is seeking third-party validation of new methods under the Homeland Security initiative. Furthermore, charting of quantitative data such as carrier counts is used to monitor the outcome of laboratory methods. In addition, the services of a statistician are available under two extramural contracts; a contract with AOAC International and with Montana State University. Statistical services are used for study design, analysis of data, and review of proficiency exercises. Uncertainty for quantitative tests will be determined using a statistical approach. First, logio- transform each data point used to determine the uncertainty and then determine the mean and standard deviation of those data points. For data sets with 20 or more data points, multiply the standard deviation by 2 to determine the expanded uncertainty (coverage factor k = 2). For data sets with less than 20 data points, determine k (find the value for n-1 degrees of freedom, where n is equal to the number of data points that make up the mean, from the Student's t Distribution Table at the 95% confidence interval) and then multiply the standard deviation by k to determine the expanded uncertainty. Uncertainty measurements will be listed as the mean ฑ k and will be recorded in a logbook. The measurements may be updated as needed (i.e., when a sufficient number of additional data points have been generated). E. EXTRAMURAL AGREEMENTS AND PROCUREMENT OF ITEMS AND SERVICES The Laboratory procures services and supplies from external vendors. The laboratory purchases media, reagents, consumable supplies, equipment, and other materials used in the conduct of laboratory studies from reputable vendors (VWR, Fisher Scientific etc.) The materials must meet the specifications outlined in a standard method or procedure. Quality checks are conducted (for example, sterility and performance of media) on a regular basis to ensure that the quality meets the laboratory's needs. Microorganisms for the studies are purchased from reputable vendors (ATCC, bioMerieux, Remel) and are checked to ensure that their culture and morphological characteristics are consistent with established standards. As part of an internal quality control program, the laboratory verifies the quality of deionized water used in making media, reagents, and to dilute disinfectants during efficacy testing. As discussed in the laboratory Standard Operating Procedure (SOP) for quality ------- BEAD/MLB July 2011 Page 24 of 3 8 assurance of purified water, de-ionized water is checked for total heavy metals, specific heavy metals (Cadmium, Lead, Nickel, Zinc, Copper, and Chromium), total organic carbon, conductivity, total chlorine residual and heterotrophic plate counts. Monitoring of total chlorine residual is performed by the EPA/OPP Microbiology Laboratory. Monitoring of total heavy metals, specific heavy metals, total organic carbon, conductivity and heterotrophic plate counts is performed by QC laboratories (1205 Industrial Blvd., Southampton, PA 18966-0514, 215-355- 3900). QC Laboratories is certified by the State of Maryland Department of Health and Mental Hygiene Laboratories Administration as a State Certified Water Quality Laboratory. Following each round of sample analysis, vendor forwards the analytical results to the OPP Microbiology laboratory. The laboratory staff analyzes the results as described in the SOP. Laboratory balances, weights, timers, NIST-traceable thermometers, hygrometers, Rees system and spectrophotometers are certified by contract vendors on an annual basis to ensure accuracy. The Vitek 2 Compact system, for automated identification of microorganisms and Pipettes (Rainin) are factory certified and serviced annually. ELISA reader verification plates are sent out for traceable certification every two years. Preventative maintenance on large equipment, including biological safety cabinets (BSCs), fume hoods, and autoclaves is provided by the building's Facility Manager. The Facility Manager utilizes outside vendors to service these pieces of equipment and to annually certify the BSCs and fume hoods. In-house calibration procedures and frequencies for other apparatus used in the laboratory are detailed in the appropriate Equipment (EQ) and Quality Control (QC) SOPs. If appropriate, ISO 17025 accredited vendors and calibration equipment are preferred. For Homeland Security-related projects, the following extramural agreements have been established following the Agency's procedures for development of extramural agreements. Any changes to the agreements or contracts are done formally, in writing, through the appropriate Agency approval process. The Agency has different requirements for oversight dependent on the funding vehicles (contracts, grants, or interagency agreements). Certified Agency project officers, familiar with the work to be done, are assigned to the extramural agreements. An Interagency Agreement (lAs) with U.S. Army Edgewood Chemical and Biological Center (ECBC), Aberdeen Proving Ground, MD. has been developed to provide funding for personnel resources and the equipment and supplies expended or consumed during the project. ECBC provide expertise and technical support in the collaborative testing of test methods, surrogates, and decontamination chemicals. The IA expires in2015. Several project initiatives will be facilitated by AOAC INTERNATIONAL (AOAC), a standard-setting organization. AOAC is under contract with MLB and will coordinate the review and third-party approval of validation protocols by a world-recognized experts, statisticians, safety advisors, and appropriate committees. AOAC will provide the experts necessary to evaluate the protocols according to relevant AOAC guidelines and policies for method modifications and validation studies. AOAC shall provide MLB with the necessary tools to ensure an expeditious review and work with MLB to ensure the protocol is in the ------- BEAD/MLB July 2011 Page 25 of 3 8 necessary format and all the components of the protocol are submitted. A contract with Montana State University (MSU) has been established to provide laboratory support for disinfectant test method development and standardization with emphasis on biofilm. In addition the MSU contract provides for statistical support and associated consultation on experimental design, protocol development, performance standards, and assistance with the preparation and presentation of oral and written materials. Dr. Martin Hamilton, Big Sky Statistical Analysts, is a statistician assisting on the MLB research initiatives. Dr. Hamilton is a sub-contractor under the AOAC contract and the MSU contract. Under OPPT's contract with Battelle, MLB will support and coordinate Homeland Security studies as necessary and as funding will allow. The EPA Deputy Project Officer assigned to the Battelle contract is Ron Morony (National Program Chemicals Division); however, MLB will prepare the Task Orders and assist in the management and review aspects. MLB contributes Homeland Security funding to ORD to support collaborative test method and surrogate studies conducted by ORD and Battelle (contractor). Contracts with the North Carolina Department of Agriculture, Ohio Department of Agriculture and Michigan Department of Agriculture laboratories to provide disinfectant efficacy testing of EPA registered hospital disinfectants and test method development. Inoculated porcelain penicylinders and spore suspensions are purchased from Presque Isle Cultures, 3804 West Lake Rd., P.O. Box 8191, Erie, PA 16505. Other Assistance Agreements The laboratory uses staff resources obtained under the National Older Worker Career Center (NOWCC) grant. These individuals are hired as research assistants and have technical backgrounds suitable to the research environment. They assist the EPA analysts with research studies, quality control procedures, preparation of media, supplies and reagents, and other activities. F. DOCUMENTS AND RECORDS I. Process for Recording and Maintaining Data Forms associated with the Standard Operating Procedures (Appendices A5 and A6) are used for documenting laboratory data and supporting information. Certain information may be documented using prepared data recording forms; these forms were developed to maintain consistency in recording of information and to provide a pre-established report format to clients. When standard forms are not available (for unique data collection activities or one time projects), the data may be recorded in a laboratory notebook following the procedures outlined in SOP- ADM-05. For tracking purposes, notebooks are pre-numbered and assigned to individual analysts. ------- BEAD/MLB July 2011 Page 26 of 3 8 The laboratory utilizes an environmental monitoring and alarm system (Rees System/EMAS) to collect environmental data electronically for refrigerators, freezers, incubators and sample storage rooms. Data is collected through a network of wireless environmental monitoring devices that use radio frequency to transmit and receive data about current conditions. The system provides emergency notifications through a phone tree if equipment falls outside the established parameters. The data from analyses of samples and the data from the ongoing QA/QC activities are reviewed by the data recorder and then peer reviewed by another staff member. Whenever the internal quality control checks or audits indicate non-conformance to accepted protocols and procedures, corrective action is taken. The vast majority of ATP data are qualitative in nature. For those methods which require construction of charts, standard curves, plotting survivors vs. time as in the Quantitative Suspension Test Method (QSTM), the curves would be developed as described in the method and as reflected in the SOP. For quantitative tests, log reduction estimates are calculated using spreadsheet software. Standard curve and calibration data generated for Enzyme-linked Immunosorbent Assay (ELISA) method validations are analyzed using Ascent Software provided with the Multiskan Ascent microplate reader. Test data will be recorded manually or automatically through computer/ instrument interfaces. A complete audit trail will follow any entry. Original copies of any hand-written results will be maintained. For the Antimicrobial Testing Program reports, the draft report is peer reviewed and then procedures are followed as specified in the SOP for generation of a final report to the client. Other reporting mechanisms may be used to report findings from laboratory studies dependent on the needs of the client. The laboratory stores the draft performance report, the final performance report, and associated memoranda by product. All raw data, performance reports and quality control records are maintained in the archive room. Records are retained in the designated space at the ESC for the length of time listed in the laboratory's retention schedule. Records are archived as specified in the retention schedule. II. Quality Assurance Records Records of routine quality control activities are recorded in laboratory notebooks. In accordance with GLP's, the laboratory's quality control practices include thorough documentation of laboratory operations; the original documents are kept on file as specified in the SOP. As SOPs are revised, the original controlled copy (O version) is marked as obsolete and retired to the archives. All other controlled copies of the SOPs are destroyed. Handwritten amendments to SOPs are not acceptable. Amendments to SOPs are issued in accordance with ADM-02. Handwritten amendments to study protocols may be allowed as necessary to conduct the study within a timely manner. The amendment is noted, initialed and dated by the analyst. If the change is deemed to be substantive by the Team Leader or Senior ------- BEAD/MLB July 2011 Page 27 of 3 8 Science Advisor, the approval of the client is attached (typically done via email). Copies of all audit reports are archived. The MLB Branch Chief, or designated staff shall be responsible for the files in the event of the QA Officer's absence. In addition, the QAO maintains electronic copies of all memoranda related to QA activities. Copies of external audits, responses, and corrective actions are maintained by the QAU and the Branch Chief. These records are maintained on paper or may be stored electronically as scanned PDF documents. III. Archives and Disposition The retention schedule for the Laboratory documents is contained in the SOP ADM-03 for Records and Archives. The records management practices for MLB are consistent with the U.S. EPA Records Schedules and the policies of the Agency's National Records Management Program. Records will be retained in the laboratory for the length of time listed in the file plan unless volume warrants a transfer to a records archive area. When the retention time for a set of records has passed, the records will be destroyed. The location of these records is in a secured room at the ESC. Individual files are kept in filing cabinets within this room. The QAO, Team Leader, Senior Science Advisor, Branch Chief and authorized analysts shall have access to these filing cabinets. G. COMPUTER HARDWARE AND SOFTWARE Computer security at the Environmental Science Center is based on the Agency's security policy for the EPA national communications network including basic controls to ensure a secure network infrastructure which integrates confidentiality, authenticity, availability, and integrity into the system. Systems are in place to protect the Agency's infrastructure and critical information assets from internal and external threats, to ensure information technology resources are consistent with a secure network design, to protect information resources from unauthorized use or threats, and to support the Agency in achieving its mission. These procedures and policies are identified by the Agency's Office of Technology Operations and Planning. All workstations at the ESC require an ID and password to login. Workstations are equipped with various programs to protect against spyware, spam, and viruses. All servers and major network equipment are placed in secure locations and the files on the servers are given certain rights for each user as they log into the network. Employees are required to take annual information security training and records management training. The Laboratory does not currently transfer raw data electronically although the laboratory may share data summaries electronically as PDF documents. Certain equipment can store data electronically such as the Vitek 2 Compact, an automated identification system for microorganisms, used in the laboratory for confirmatory organism identification. Software for the systems is upgraded when necessary during annual maintenance. Another system which stores data electronically is the Rees environmental monitoring and alarm system (EMAS) which ------- BEAD/MLB July 2011 Page 28 of 3 8 monitors temperatures of refrigerators, freezers, incubators and sample storage rooms. The EMAS is loaded on a small stand alone computer and is password protected. An ESC facility-wide Chemical Inventory Management System (ChIMฎ by Vertere) is used by the OPP Microbiology Laboratory to track reagents and media. Functionality of the System includes: Chemical Identification, Individual Item tracking, Safety Data, and Inventory History. The chemical inventory management system, or ChEVI, enables users to search a database to determine if a needed chemical is already present in the laboratory. The software meets the Agency's standards. The laboratory has developed an automated system for maintaining an inventory and tracking expiration dates for laboratory chemicals, reagents, and other materials in Access. The laboratory will use standard Agency software (Access, Excel) to chart certain information such as carrier counts, media performance etc., in order to identify outlier data points and information. Results obtained by the laboratories involved in the Antimicrobial Testing Program are being entered into an Oracle database so that trends or unusual findings can be monitored. Files that are maintained in electronic format using standard Agency software are subject to the same retention schedule. They may be maintained on user share files or other electronic storage systems. H. PLANNING In FY 2011/2012, the laboratory will continue with antimicrobial efficacy initiatives, Homeland Security related research, biofilm, PCR based methodology, and efficacy method research and development. Antimicrobial product testing will continue at the laboratory under the Direct Shipment initiative and through the official sample collection process. Testing support is provided by the three state laboratories under contract to the Agency. Laboratory projects are captured on the OPP Microbiology Laboratory Branch FY 2011 and 2012 Annual Workplans. New initiatives are reviewed and approved at the Branch Chief level consistent with the OPP Program goals. The laboratory works closely with the client base in the development of the yearly work plans to ensure that the laboratory projects mesh with the needs of the regulatory programs. For new projects outside the regular core programs, such as research projects or collaborative exercises, the laboratory will develop a QAPP for each project. The QAPP will include the necessary criteria such as project manager, goals, schedule, type of data to be generated, performance measures, QA/QC activities, audits, requirements for analysis of data, appropriate statistical measures, and other parameters necessary to ensure the validity and reliability of the data. Each Quality Assurance Project Plan will be reviewed and approved by the laboratory's Quality Assurance Officer prior to initiating the project. Annual, internal technical and system audits will be conducted by the QAO based on the testing/research schedule of the laboratory and any issues identified through prior audits. These ------- BEAD/MLB July 2011 Page 29 of 3 8 audits will be both scheduled and unannounced. The tentative schedule will be developed by the QAO and Team Leader in the first quarter of each fiscal year and adjusted to accommodate events such as changes in sample collection receipts or new collaborative testing. The laboratory will request audits from external sources annually. These audits may cover technical, management system, and GLP reviews. The Laboratory will consult with the OPP Director of Quality Assurance in scheduling these audits. In addition, the Microbiology laboratory, along with other BEAD laboratories, are seeking ISO 17025 accreditation for selected methods as defined in the scope of accreditation, and meets the requirements of the ISO standard. I. IMPLEMENTATION OF WORK PROCESSES The senior management for the program is responsible for ensuring that the work is implemented according to the developed schedule and plan. As operations or priorities change, the management will identify the critical processes that are necessary to ensure the validity of the data. If the changing priorities require the development of new SOPs, revisions to the QMP, or implementation of QAPP's, the management is responsible for the development of the necessary quality assurance practices. Any change which may impact the quality of the data generated by the laboratory will be done formally through the QAO. The current Standard Operating Procedures for the laboratory are assigned control numbers. The laboratory's quality assurance officer is responsible for assigning the control copy numbers. If changes are made the QAO will verify that revisions are appropriate, that the review and signature procedures are followed, and the previous version is appended, or retired and the new SOP is put into practice. The laboratory Team Leader is responsible for the development of the routine product testing and method development work related to efficacy test methods. If the work is interrupted or unanticipated problems occur, he/she will revise the schedule accordingly. The laboratory Senior Science Advisor is responsible for the technical direction of the laboratory programs and provides oversight and technical guidance to the laboratory scientists and oversight to the extramural agreements for Homeland Security initiatives. Work processes for methods under the ISO 17025 standard will be adjusted to ensure consistent adherence to the requirements outlined in the standard with particular attention to non- conformances, corrective and preventive actions, and addressing customer complaints. These activities will require additional time on the part of the laboratory staff and management. J. ASSESSMENT AND RESPONSE The generation of quality data is the responsibility of each laboratory employee. Each individual on the laboratory team is trained on the use of laboratory equipment, quality control practices, characteristics of the microorganisms, confirmatory techniques, recording of data ------- BEAD/MLB July 2011 Page 30 of 38 elements, appropriate means of correcting any entry errors, and other daily operational activities which may impact the validity of the generated data. Adherence to appropriate quality control and quality assurance activities is identified as a critical element in each laboratory employee's performance standard. The QAU will conduct audits of ongoing studies as outlined in the laboratory SOP (QA- 01: Functions of the Quality Assurance unit). An audit schedule is developed each year to conduct in-lab inspections of certain procedures, review books and records, and arrange for external audits. The results are documented and provided to the analysts, Team Leader, Senior Science Advisor and Branch Chief. If during an audit, the QAU determines that significant deviations or factors were observed that call into question the validity of the data or the procedure, the unit may recommend that the study be terminated and repeated using the appropriate procedures. The study is deemed to be terminated and a formal memorandum to the file is prepared which notes the circumstances under which the study was found to be lacking. The QAU recommends and follows up on corrective actions and maintains the corrective action file. The QAO will review the results of proficiency testing, once the program is developed, with the laboratory Team Leader and Senior Science Advisor and make recommendations for follow-up action, if required. The QAO has authority to audit any laboratory data or practices. Any deficiencies will be brought to the attention of the Team Leader, Senior Science Advisor and Branch Chief and immediate action will be taken to correct the deficiencies. The QAO will recommend external audits as appropriate. These audits are typically done with a team of Agency scientists with expertise in microbiology and chemistry. The audit team presents results to the laboratory management and corrective action is the responsibility of the senior management team. External audits for the purposes of determining compliance with the Good Laboratory Practices, system documentation, and management review are arranged on a regular basis consistent with the annual audit schedule. The findings are documented and reviewed by the Branch Chief and Quality Assurance Unit. Any corrective actions that are taken are documented and maintained by the QAU. A formal response is provided to the external auditor by the Branch Chief. The response identifies the deficiencies, corrective actions, and any follow up activities that are planned. Preventive action plans are developed to prevent the problems from occurring in the future. The laboratory uses a variety of management tools to ensure adequate planning, documentation and to verify the integrity and the accuracy of the work. Project specific planning is done thru the development of QAPPs and study protocols. Audits are conducted to ensure compliance with the SOPs, study protocols, and the QA systems. Assessments include internal and external audits, observations, peer review of data, quality control checks of equipment, supplies and materials, performance evaluations, and management and system reviews. The workplan is revisited on a quarterly basis to determine the adequacy of personnel and other ------- BEAD/MLB July 2011 Page 31 of 38 resources to accomplish the established goals. Overall audit findings, corrective actions taken, staff training, and customer comments and complaints are reviewed by the Branch Chief and QAU to evaluate the effectiveness of the laboratory's quality programs. K. QUALITY IMPROVEMENT The current practices and activities identified in the QA management plan work to ensure the validity and reliability of the data generated by the laboratory. The internal audits, external audits, and review schedule of the SOPs provide opportunities for assessment and improvement of the quality systems. Communications between the laboratory team, quality assurance officer, and management encourage the exchange of information which is necessary to improve ongoing activities. The team meets on a regular basis to exchange information and to make improvements to data forms, SOPs, and facility practices. The team is integrating automation into the current practices. The team also interfaces with laboratory customers and support services to share information and exchange ideas. L. REFERENCES 1. OPP Microbiology laboratory, Antimicrobial Testing Program - Quality Assurance Project Plan (ATP-QAPP) 2. OPP Microbiology laboratory Plant Incorporated Protectant QAPP (PIP-QAPP-2007-01) 3. OPP MLB Homeland Security QAPP (HS-QAPP-2010) 4. OPP Microbiology Laboratory Biofilm QAPP (BF-QAPP- 2008) 5. OPP Microbiology laboratory Virology Testing Program QAPP (VTP-QAPP-2008) 6. OPP Microbiology Laboratory Fiscal Year 2011 Work plan 7. OPP Microbiology Laboratory Response to the EPA Laboratory Competency Policy Directive, Implementation Plan 8. Office of Pesticide Programs, Quality Management Plan, 2006 9. Microbiology Laboratory Branch Standard Operating Procedures (see Appendix A-4). ------- BEAD/MLB July 2011 Page 32 of 38 M. LIST OF APPENDICES Appendix A-l: Organizational Chart - Office of Pesticide Programs Appendix A-2: Organizational Chart - Biological and Economic Analysis Division Appendix A-3: OPP Microbiology Laboratory- Quality Assurance Organization Appendix A-4: Index of Antimicrobial Testing Program (ATP) Standard Operating Procedures Appendix A-5: Index of Plant Incorporated Protectant (PIP) Standard Operating Procedures ------- BEAD/MLB July 2011 Page 33 of 38 APPENDIX A-l ORGANIZATION OF OPP OFFICE OF PESTICIDE PROGRAMS IMMEDIATE OFFICE OF THE DIRECTOR RESOURCES MANAGEMENT STAFF FIELD & EXTERNAL AFFAIRS DIVISION BIOPESTICIDES & POLLUTION PREVENTION DIVISION REGISTRATION DIVISION ENVIRONMENTAL FATE & EFFECTS DIVISION SCIENCE INFORMATION & ANALYSIS DIVISION ANTIMICROBIALS DIVISION PESTICIDE RE- EVALUATION DIVISION HEALTH EFFECTS DIVISION BIOLOGICAL & ECONOMIC ANALYSIS DIVISION ------- BEAD/MLB July 2011 Page 34 of 38 APPENDIX A-2 ORGANIZATION OF BIOLOGICAL AND ECONOMIC ANALYSIS DIVISION Environmental Chemistry Lab (Bay St. Louis) Analytical Chemistry Lab Director Associate Director Economic Analysis Branch Herbicide Microt & Laboi Insecticide Bra Branch jiology Science "atory Information nch & Analysis Branch ------- Appendix 3 OPP-Microbiology Laboratory Quality Assurance Organization BEAD/MLB July 2011 Page 35 of 38 Jack Housenger Director OPP/BEAD 703-305-8163 Interagency agreement ECBC Lisa Smith ASPH (Association of Schools of Public Health) Erick Christensen Susan Lawrence Branch Chief OPP Microbiology Laboratory 410-305-2954 OPP-Microbiology Laboratory Quality Assurance Kiran Verma Quality Assurance Officer 410-305-2957 OPP- Microbiology Laboratory Scientists: -M.Jason Duncan -Jafrul Hasan -Knoxley Japal -Rebecca Pines -Marc Rindal -Luisa Samalot-Freire -Stephen Tomasino -Ella Witherspoon -Ann Broderick -Charles Odeyale -Denis Franks -Michele Cottrill OPP-Quality Assurance Denise Rice Director 703- 347-0282 Michele Cottrill Alternate Quality Assurance Officer and Laboratory Scientist Legend: Solid One-Way Arrow = Supervisory Dashed One-Way Arrow =Advisory/Team Leader ^^ Dashed Two-Way Arrow = Advisory and Collaboration ------- BEAD/MLB July 2011 Page 36 of 38 APPENDIX A-4 Index of ATP Standard Operating Procedures OPP Microbiology Laboratory Antimicrobial Testing Program SOPs SOP EQ-01-05 EQ-02-05 EQ-03-04 EQ-04-04 EQ-05-04 EQ-06-04 EQ-08-05 EQ-09-01 EQ-10-00 MB-01-05 MB-02-04 MB-03-04 MB-05-08 MB-06-05 MB-07-05 MB-09-04 MB-10-03 MB- 11 -03 MB- 13 -03 MB-15-02 MB- 16-01 MB- 17-01 MB-18-00 MB- 19-01 MB-21-00 Title Calibration and Maintenance of pH Meters Maintenance and Calibration of Thermometers and Thermometers/hygrometers Calibration and Maintenance of Weigh Balances Systems Check for the Beckman (DU Series 500) Spectrophotometer Calibration and Maintenance of Timers Calibration of Kimble Class A Burets Verification of Volume Dispensed and Maintenance of Oxford Automatic Dispenser and Hamilton Microlab 500 Use of Petrifilm and Petriscan for Research Applications Use and Maintenance of Orbital Shakers Biosafety in the Laboratory Tracking of Test Microorganisms Screening Carriers Used in Disinfectant Efficacy Testing AOAC Use Dilution Method for Testing Disinfectants Germicidal Spray Products as Disinfectants Against Staphylococcus aureus, Pseudomonas aeruginosa, and Mycobacterium bovis (BCG) Tuberculocidal Activity of Disinfectants: II Confirmative in vitro test for Determining Tuberculocidal Activity. Disinfectant Towel ette Test against S. aureus and P. aeruginosa and S. enterica Media and Reagents Used in Microbiological assays Including Performance Assessment and Sterility Verification Neutralization Confirmation Assay for Disinfectant Products Tested Against Mycobacterium bovis (BCG) Handling Spills of Biohazardous Material AOAC Sporicidal Activity of disinfectants Test (Bacillus x porcelain comp.) Quantitative Suspension Test Method for Determining Tuberculocidal Efficacy of Disinfectants Against Mycobacterium bovis (BCG) Neutralization Conf. Procedure for Products Evaluated with the AOAC UDM and AOAC GSPT (S. aureus, P. aeruginosa and S. enterica) Bio-safety Practices for Handling Select Agent in room (D-122) SOP for Growing a P. aeruginosa Biofilm Using the CDC Biofilm Reactor Quantitative TSM for efficacy of Liquid sporicides against spores ofB.subtilis on a Hard Non-porous Surface ------- BEAD/MLB July 2011 Page 37 of 38 Antimicrobial Testing Program SOPs SOP MB-22-00 MB-23-00 MB-24-01 MB-25-00 QC-01-04 QC-02-04 QC-03-06 QC-05-05 QC-06-04 QC-08-04 QC-09-04 QC-13-04 QC-18-04 QC-19-05 QC-21-01 QC-22-02 QC-23-01 QA-01-04 QA-04-04 ADM-01-04 ADM-02-03 ADM-03-03 ADM-04-02 ADM-05-02 ADM-06-01 ADM-07-00 ADM-08-00 COC-01-04 VTP-01-01 VTP-02-01 VTP-03-01 Title Disinfectant Sample Preparation Disinfectant Towel ette test against M. bovis (BCG) Testing of M bovis using the Germicidal Spray Products as Disinfectants Test OECD Quantitative method for evaluating bactericidal activity of microbicides used on hard, non-porous surfaces Quality Assurance of Purified Water Monitoring of Laboratories for airborne contaminants Glass Washing and Detergent Residues Test Monitoring Environmental parameters of Incubators, Refrigerators, and Freezers, Labs and Sample Storage Rooms Use and Maintenance of Biological Safety Cabinets Monitoring Temperature/Humidity of the Sample Storage Room Establishment of Control Numbers and Tracking Laboratory Supplies Performance Verification of Autoclaves Sterility Assessment of Disinfectant Product Samples Verification of Digital Pipettes Using the PCS 2 Pipette Calibration System Determining the Presence of Microbial Contamination in Disinfectant Products VITEK 2 Compact: Use, Maintenance and Quality Control Procedures Performance Verification of the Yamato Drying Oven Quality Assurance Unit and its Functions Preparation and Maintenance of Master Schedule Preparation and Review of Performance Reports for Efficacy Testing Preparation and Review of Standard Operating Procedures (SOPs) Records and Archives OPP Microbiology Laboratory Training Guidelines for Use and Maint. of Laboratory Notebooks and Project Binders Customer feedback/complaints Non-conformance reports Corrective and Preventive Actions Disinfectant Sample Login and Tracking Initiation Propagation & Preservation of Crandell Rees Feline Kidney cell line Initiation Propagation Enumeration & preservation of feline calicivirus Virucidal effectiveness test using feline calicivirus as surrogate for Norovirus ------- BEAD/MLB July 2011 Page 38 of 38 APPENDIX A-5 Index of PIP Standard Operating Procedures OPP Microbiology Laboratory Plant Incorporated Protectant Method Validation Program SOPs 01 02 03 04 05 06 07 08 09 10 11 PIP-ADM-01-01 PIP-COC-01-01 PIP-EQ-01-01 PIP-EQ-02-01 PIP-EQ-03-01 PIP-EQ-04-01 PIP-EQ-05-01 PIP-EQ-06-01 PIP-EQ-07-01 PIP-MB-01-01 PIP-MB-02-01 Use of Lab oratory Notebooks Plant Incorporated Protectant Method Validation Program Login and Tracking of Technical Materials Performance Verification of the GeneAmp PCR System 9700 Performance Verification of PCR Amplification in the PE Biosystems GeneAmp PCR System 9700 Performance Verification and Maintenance of the Microplate Photometer Operation and Maintenance of the Eppendorf Centrifuge Model 5804R Operation and Maintenance of the Labsystems Wellwash 4 Mk 2 Automatic Microplate Washer Use and Maintenance of the Rainin Single Channel Pipettes, Multi-channel Pipettes, and Repeater Pipette Use and Maintenance of the Polytron PT 3 100 Laboratory Homogenizer Workflow Through the Laboratory Conducting a Method Validation Pre-Review ------- |