Attachment_1-Pathology_PWS.doc

Attachment #1, NCTR On-Site Pathology Services Performance Work Statement (PWS)

1. Background. The National Center for Toxicological Research (NCTR) is located at the Jefferson Laboratories of the U.S. Food and Drug Administration (FDA) in Jefferson, Arkansas, approximately 35 miles south of Little Rock and 28 miles north of Pine Bluff. NCTR is an internationally recognized FDA research center that conducts toxicological research studies and other research activities designed to support the FDA’s mission to protect the public’s health. NCTR investigators partner with researchers elsewhere in the FDA as well as other government agencies, industry, and academia. FDA/NCTR and the National Institute of Environmental Health Sciences (NIEHS) have had an interagency agreement (IAG) since 1992, through which the FDA collaborates with the National Toxicology Program (NTP) to design and conduct toxicological studies involving compounds of regulatory interest to the FDA. NCTR is comprised of six research divisions and has facilities including: 132 general or special purpose research laboratories; AAALAC-accredited animal facilities, including rodent facilities accommodating conventional housing, a specific pathogen free rodent production colony, isolators for germ-free rodents, and quarantine; a non-human primate research center; a zebrafish production facility; a phototoxicology research center; an imaging center including microPET, MRI, and CT scanner; a nanotechnology core facility; and an inhalation toxicology facility. On-site pathology services for the animal studies performed at NCTR have been obtained through contracts since the Center’s inception in 1972.

2. DEFINITIONS. As used throughout this PWS, the following terms shall have the meaning set forth below and specified as applicable to this project.

2.1. AAALAC Accreditation. The Association for Assessment and Accreditation of Laboratory Animal Care International is a private, nonprofit organization that evaluates institutions that use animals in research, teaching, or testing and awards accreditation to those that meet or exceed the standards for humane treatment of animals outlined in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011), the Guide for the Care and Use of Agricultural Animals in Research and Teaching (Federation of Animal Science Societies, 2010), and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purpose (Council of Europe, ETS 123).

2.2. Center for Tobacco Products (CTP). CTP, a part of the FDA, oversees the implementation of the Family Smoking Prevention and Tobacco Control Act.

2.3. Contracting Officer (CO). A Government employee with the authority to enter into and administer contracts and make determinations and findings with respect thereto, or with part of such authority.

2.4. Contracting Officer’s Representative (COR). A Government employee who provides technical clarification and guidance with respect to the PWS and serves as the technical liaison between the Contractor and the CO.

2.5. Contractor. Refers to both the Prime Contractor and all Subcontractors. The Prime Contractor shall be responsible for ensuring that its Subcontractors comply with the requirements of this PWS.

2.6. Contractor Performance Assessment Reporting System (CPARS). The Government’s automated system for reporting Contractor performance in at least the following areas: Quality of Product or Service; Scheduling; Cost Control; Business Relations; Management of Key Personnel; and Utilization of Small Business (subcontracting). (CPARS training: https://www.cpars.csd.disa.mil/allapps/cpartrng/webtrain/webtrain_all.htm)

2.7. Cooperative Research and Development Agreement (CRADA). A CRADA is an agreement between one or more FDA laboratories and one or more non-Federal parties under which the FDA laboratory provides personnel, services, facilities, equipment, or other resources toward the conduct of specified research or development efforts. The CRADA partner contributes all of the above and funding to the project.

2.8. Document View+ (DocView). DocView is an Oracle-based customized tool in the Government’s Unified Financial Management System that allows the user to search for and view commitment and obligation records by various data elements and document information, but does not allow users to change data.

2.9. Good Laboratory Practice (GLP). A set of regulations that applies to animal and non-animal research and safety studies funded or reviewed by the FDA. The regulations are a quality system of management controls for research laboratories and organizations to try to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of non-clinical safety tests. (21CFR, Part 58; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=58&showFR=1).

2.10. Government Furnished Property (GFP). All Government facilities, property, and supplies provided to the Contractor to be used by the Contractor in carrying out responsibilities set forth in this PWS. Ownership of GFP remains that of the Government at all times (unless and until consumed or expended in the normal course of business) and all GFP shall be returned or accounted for upon completion of the contract.

2.11. Interagency Agreement (IAG). A document between government agencies and departments that defines cooperative work between the agencies. The IAG between FDA/NCTR and NIEHS/NTP has been in place since 1992. The IAG supports the design and execution of toxicological studies that are consistent with the goals and needs of both the FDA and NTP.

2.12. NCTR Experiment Activity Tracking (NEAT). A computerized system to track time spent on individual experiments and other activities. Each experiment or activity in the system is capable of being broken down into a number of milestones with individual tasks to accurately track how time was spent on the experiment or activity.

2.13. National Institute of Environmental Health Sciences (NIEHS). Located in Research Triangle Park, North Carolina, NIEHS is a part of the National Institutes of Health (NIH), and has a mission to discover how the environment affects people in order to promote healthier lives.

2.14. National Toxicology Program (NTP). The NTP is an interagency program whose mission is to evaluate agents of public health concern by developing and applying tools of modern toxicology and molecular biology.

2.15. Occupational Safety and Health Administration (OSHA). As part of the U.S. Department of Labor, OSHA sets and enforces standards to assure safe and healthful working conditions for working men and women. OSHA Standards, 29 CFR 1910 and 1925: http://www.osha.gov/pls/oshaweb/owasrch.search_form?p_doc_type=STANDARDS&p_toc_level=0

2.16. Office of Scientific Coordination (OSC). The office of the NCTR Liaison to the NTP. OSC coordinates all NTP studies at NCTR and manages the IAG with NIEHS/NTP. The COR is part of this organization.

2.17. Organisation for Economic Co-operation and Development (OECD) Test Guidelines. A collection of the most relevant internationally agreed test methods used by government, industry, and independent laboratories to determine the safety of chemicals and chemical preparations (http://www.oecd.org/env/ehs/testing/oecdguidelinesforthetestingofchemicals.htm).

2.18. Past Performance Information Retrieval System (PPIRS). A web-enabled, government-wide application that provides timely and pertinent contractor past performance information to the Federal acquisition community for use in making source selection decisions. Reports from CPARS are transmitted to PPIRS. Government access to PPIRS is restricted to those who are working on source selections and Contractor access is restricted to viewing only data regarding their contract. PPIRS registration: http://www.federalcontractorregistry.com/?gclid=COuDgOyOpLwCFcdQOgodPHMAqA.

2.19. Pathology Tracking System. An Oracle-based database used to track the various steps involved in the pathology processing of animal tissue, from receiving the animal to archiving wet tissues, blocks, and slides.

2.20. Pathology Working Group (PWG). A group of pathologists from the NCTR Contractor, NTP, and the NTP Pathology Contractor. The group meets to resolve any discrepancies between the findings of the study pathologist(s) and the reviewing pathologist(s) from the Quality Assessment (QAS). When the group reaches consensus, the PWG confirms the histopathology of treatment-related findings.

2.21. Principal Investigator (PI). The PI is the lead scientist with ultimate responsibility for a research protocol. The terms “PI” and “study director” are used interchangeably.

2.22. Protocol. Protocols are experimental designs written by Principal Investigators, approved through NCTR management, and performed at NCTR. The terms “protocol” and “study” are used interchangeably.

2.23. Quality Assessment (QAS). Independent pathology peer review of diagnoses on NTP studies, including a pathology data review, an audit of pathology specimens, and quality assurance of histopathology.

2.24. Quality Assurance Surveillance Plan (QASP). The plan developed specifically for the PWS, to assure compliance with the requirements. This should not be confused with the Contractor’s internal Quality Assurance (QA) required by GLP guidelines.

2.25. Quality Assurance Unit (QAU). The NCTR QAU in the Regulatory Compliance and Risk Management office conducts audits, inspections, and reviews to assess compliance with approved study protocols, established Standard Operating Procedures (SOPs), and the FDA’s GLP for Nonclinical Laboratory Studies (21 CFR Part 58). QAU observations are reported to the responsible laboratory personnel, study director, investigators, and management. Corrective action responses as a result of a QAU observation include: protocol amendments; protocol/data/report/SOP clarifications and/or revisions; and protocol/SOP deviation documentation.

2.26. Quality Control Plan (QCP). A document that includes all measures to be taken by the Contractor to ensure that the quality of an end item service meets the contract requirements regarding timeliness, accuracy, appearance, completeness, consistency, and conformity to appropriate standards and/or specifications. It includes, but is not limited to, a written set of self-inspection checklists developed by the Contractor that comprehensively detect variations from the contract requirements; recording of work data; trend analysis; feedback and control systems for correcting deficiencies; and the necessary documentation to record findings.

2.27. Regulatory Compliance and Risk Management (RCRM). RCRM is the office responsible for NCTR’s Safety, Security, Archives, and QAU. Federal employees in this office conduct laboratory safety training and inspections, as well as QA inspections.

2.28. Restricted Areas. Special clearance procedures are required for access to the Non-Human Primate (NHP) facility. Access to the NHP facility may be obtained when the following criteria are met: 1) legitimate need to enter the facility; 2) completion of NCTR NHP safety training; 3) negative tuberculosis test, positive measles titer, and respirator fit test; 4) NHP Facility Supervisor briefing; and 5) approval from the Director of Veterinary Services. In addition, access to the rodent breeding colony (a Specified Pathogen Free [SPF] area) is restricted so that no one may enter after previously having been in a conventional rodent facility on the same day. While in these areas, Contractor personnel are subject to applicable Jefferson Laboratories SOPs, which will be made available to those who are permitted access.

2.29. Standard Operating Procedures (SOPs). A formally documented specific set of procedures to be followed in carrying out a given operation or in a given situation.

2.30. Study. Studies are experimental designs written by PIs, approved through NCTR management and performed at NCTR. The terms “protocol” and “study” are used interchangeably.

2.31. Study Director. The study director is the lead scientist with ultimate responsibility for a research protocol. The terms “PI” and “study director” are used interchangeably.

2.32. Study Materials. Study materials include blocks, slides, wet tissues, and the associated paperwork for a given study.

2.33. Toxicology Study Selection and Review Committee (TSSRC). Committee responsible for monitoring the work performed under the IAG between NIEHS/NTP and NCTR. Members include the FDA/NCTR NTP Liaison, the NIEHS/NTP Project Officer, the NCTR Director, scientists from each of the FDA Centers, NIEHS scientists, and invited subject matter experts. The TSSRC meets semi-annually to review planned and ongoing NTP studies being performed at NCTR.

3. LIST OF APPENDICES.

Appendix 1:

Historical and Estimated Workload

Appendix 2:

User Guides for Electronic Systems Appendix 3:

Quality Assurance Surveillance Plan (QASP)

Appendix 4:

Floor Plans for Pathology Facility

Appendix 5:

Government Provided Equipment (GFP)

4. SCOPE OF WORK.

4.1. General Information. Research protocols written by the PIs determine pathology support requirements, which range from necropsy of a few animals and collection of a few tissues to complete necropsy of over a thousand animals requiring special handling of tissues, histopathology, special staining or other techniques (immunohistochemistry, digital imaging, etc.), hematology, urinalysis, and/or clinical chemistry. Other required techniques include, but are not limited to, teratology techniques, reproductive and developmental toxicology techniques, respiratory pathology techniques (inhalation toxicology studies), sperm morphology and motility analysis, vaginal cytology, vaginal smears for sperm evaluations, and mammary whole mounts. The Contractor shall ensure that all protocol pathology requirements are followed with particular attention to detail.

The services listed above are based on those performed on previous studies; however, each protocol dictates the methods/techniques to be used when performing the studies. Future protocols are likely to require services outside of those listed above and the routine repertoire of the industry. The Contractor shall be responsible for completing all required services, to include any necessary staff training (including On-The-Job and classroom), research and/or development of new methods, etc., associated with the procedures of each protocol.

The Contractor shall conduct the pathology services following all applicable rules, policies, regulations and guidelines set-forth herein and in each individual protocol. It is the responsibility of the Contractor to be knowledgeable and trained on the standards of operation of the studies to produce quality results.

See Appendix 1, Historical and Estimated Workload Data, for additional information on past, on-going, and anticipated future studies.

4.2. Major Services and Functional Support Areas. The Contractor shall provide all labor to include but not be limited to supervision, administrative, and technical support, to plan, schedule, coordinate, and assure effective completion of all services described herein. The major services and functional support areas are described below.

4.2.1. Administrative Services and Management. The Contractor shall provide complete on-site project management and supervision to carry out all of the terms and conditions of this PWS. All work within the areas outlined in this document shall be performed by qualified professional or technical staff (see Section 4.3 “Qualifications”).

4.2.1.1. Environment, Health, and Safety. The Contractor shall be responsible and qualified to handle all health and safety with a point of contact to be provided to the COR upon appointment. The appointed, qualified point of contact for the Contractor shall serve as the liaison to the Jefferson Laboratories Environment, Safety, and Health Committee.

4.2.1.2. Standard Operating Procedures (SOPs). SOPs for areas, operations, and procedures directly within the Contractor's responsibility shall be written and maintained by the Contractor to reflect the current procedures used by their firm. The Contractor shall enforce SOPs to ensure that procedures are conducted as specified. The Contractor shall be responsible for developing its own SOPs without direction from the Government. All SOPs shall be delivered to the COR and NCTR’s QAU for review.

Review of SOPs by the COR or NCTR’s QAU prior to finalizing and placing into service is not intended as, and shall not be construed as, approval or any assumption of responsibility or liability by the Government.

During periods of Contractor transition, the new Contractor shall perform services under guidelines of SOPs in place at the time duties are assumed and until such time that the new Contractor’s SOPs have been written and are in place.

4.2.1.3. Government Furnished Property (GFP). Government furnished property and services are discussed in Section 5. The Contractor shall manage GFP in accordance with Section 5 and the following additional details.

4.2.1.3.1. Purchasing. The Contractor shall maintain a working stock of supplies required for the performance of the work under this contract. In addition, as equipment becomes unreliable or breaks down or as new equipment is otherwise required to perform the work under this contract (e.g., a new technique requested by the Government requires equipment or more storage containers/cabinets/etc. are needed for archiving materials), the Contractor shall notify the COR to get confirmation that the equipment is necessary. For purchasing supplies and equipment, the Contractor shall follow the procedure below.

The Contractor shall enter all purchase requests into the Government’s procurement system, iProcurement. The Government will provide training for the use of iProcurement. The COR shall approve pathology Contractor orders in the iProcurement system. When orders for supplies have been completely approved through iProcurement, the Contractor shall provide the documentation for each purchase (e.g., quotes from vendors, required requisition forms), along with iProcurement approval documentation, to the COR for purchase.

The Contractor shall keep records of all documentation for all purchases, including iProcurement approvals, any quotes provided, order confirmations (if available), invoices, and packing slips, and shall provide the records to the COR upon completion of the contract or at any time upon the request of the COR or the CO. The Contractor shall reconcile the purchases for pathology on the monthly Government Purchase Card (Pcard) statement. The Contractor shall monitor the funding balance in the DocView system (training for this system will be provided by the Government) provided for pathology purchases and shall provide the COR at least one month’s notice if the balance will become insufficient to cover the remaining estimated costs for materials and supplies for the fiscal year.

4.2.1.3.2. Records/Audits. The Contractor shall maintain an accurate record of all GFP, including accountable property, which shall be part of the annual Government inventory process, and non-accountable property. The Contractor shall provide the inventory to the COR at least on an annual basis. The Contractor is responsible for turn-in of obsolete and unused equipment.

4.2.1.4. Protocols. The pathology services required under this contract are dictated by NCTR management-approved research protocols written by NCTR PIs and processed through the NCTR Office of Management Planning and Resource Management (Planning).

4.2.1.4.1. Labor and cost estimates. Prior to approval, protocols are distributed electronically to all support service areas, including to the pathology Contractor, with a message describing the requested information and listing the responsible PI and the deadline for providing the information. After a protocol from Planning is received by the Contractor, the Contractor shall calculate the cost of materials and supplies and the hours of labor required to perform the pathology portion of the protocol and provide this information to the COR within the timeframe specified. When necessary, the Contractor shall contact the responsible PI to obtain clarification of protocol parameters to provide the most accurate estimate of costs and hours possible.

The Contractor shall notify the COR if/when the pathology portion of the final approved protocol differs from the original protocol for which estimates were derived resulting in an increase in cost or hours. Upon concurrence of the increase with the COR, the Contractor shall provide an updated estimate for the change.

4.2.1.4.2. Scheduling. The Contractor shall maintain a pathology schedule to ensure that work for all protocols is performed efficiently. After a protocol has been approved through NCTR management, the Contractor, when necessary, shall contact the PI to schedule the pathology portion of the protocol and to get clarification of the details of the pathology services requested. The Contractor shall maintain an electronic pathology schedule that is always accessible to NCTR PIs for planning purposes.

4.2.1.4.3. Professional Services. The Contractor shall collaborate with PIs on issues including, but not limited to, design of protocols; development of methods; and interpretation of results.

4.2.1.5. Tracking Expended Resources. The Contractor shall track all labor hours and all tasks performed using Government-supplied electronic systems. The Contractor shall use data from these systems to provide accurate monthly reports of labor and supplies spent on individual protocols and other support functions as described in Section 6.4 below. The Government-supplied electronic tracking systems are described below. The Government shall provide training for these systems.

4.2.1.5.1. NCTR Experiment Activity Tracking (NEAT). The Contractor shall enter all time spent working on this contract into NEAT. This system tracks time spent working on individual protocols. Time spent on activities that are not directly associated with an individual protocol is also tracked by assigning the activities to tracked support functions (e.g., methods development, time spent ordering supplies). The user guide for NEAT is in Appendix 2.

4.2.1.5.2. Pathology Tracking System (Path Track). The Contractor shall enter the number of specific tasks performed for each study, from receiving the animal through archiving the wet tissue, blocks, and slides, into Path Track. For example, each time an animal is necropsied counts as one (1) necropsy and each slide (containing one or more tissues) counts as one (1) slide. The user guide for Path Track is in Appendix 2.

4.2.2. Gross Pathology. Necropsy services will be protocol-dependent. The Contractor shall follow the requirements of the protocol.

The Contractor shall perform rodent and zebrafish necropsies in the Pathology facilities, unless the protocol requires that the necropsies be performed in a different location. The Contractor shall perform non-human primate necropsies in the restricted Non-human Primate facility (see Section 2.28 regarding access to restricted areas). The Contractor shall provide “colony maintenance” (described below) for rodent and non-human primate colonies and the zebrafish production facility.

4.2.2.1. Anesthesia/Euthanasia. The Contractor shall perform anesthesia and euthanasia methods in accordance with the most current issue of the American Veterinary Medical Association euthanasia guidelines (which may be found at: https://www.avma.org/KB/Policies/Pages/Euthanasia-Guidelines.aspx?utm_source=prettyurl&utm_medium=web&utm_campaign=redirect&utm_term=issues-animal_welfare-euthanasia-pdf) and with the approved protocol.

The Contractor shall perform euthanasia on study animals and any moribund animals that the attending veterinarian has declared must be euthanized. Each protocol will dictate the method of anesthesia and euthanasia. These methods may include, but are not limited to, carbon dioxide asphyxiation, administration of barbiturates, exsanguination, decapitation, and administration of isofluorane via inhalation. For zebrafish, anesthesia and euthanasia may involve, but not be limited to, the use of MS 222 solution. Some protocols shall require anesthesia for blood collection prior to euthanasia.

4.2.2.2. Necropsy. The Contractor shall perform necropsies on a diverse range of immature (i.e., embryo, fetus, infant, juvenile), adult, and pregnant laboratory animal species.

The Contractor shall follow the parameters of each approved protocol during necropsy. Animal receipt, necropsy, and body/organ weights are documented in the Gross Pathology System (GPS; user guide in Appendix 2). Necropsy may include, but not be limited to: the documentation of receipt of animals; the documentation of animal weight; the documentation of gross abnormalities or lesions; the collection of any or all tissue and fluid samples; the preparation of mammary gland whole mounts; the documentation of organ weight; the determination of uterine implantation and resorption sites; the photography of whole animals or lesions; the perfusion of specific organs or whole animals; the lavage of tissues; the preparation and freezing of tissues, and the fixation of tissues.

Non-routine necropsy techniques shall be required by some approved protocols, including, but not limited to, sterile technique, RNase-free technique, techniques to eliminate use of a particular metal or set of metals, and techniques to minimize cross-contamination.

4.2.2.3. Colony Maintenance. The Contractor shall provide euthanasia, necropsy, and any other techniques required to determine the cause of any deaths or morbidity discovered in the rodent and non-human primate colonies and in the zebrafish production facility maintained at NCTR. The FDA veterinarian on duty normally determines whether moribund animals require euthanasia, however, the PI, other study personnel, or the veterinarian of the NCTR Animal Care Contractor may make the determination. These necropsies are by nature unscheduled, but shall be performed as soon as possible to minimize pain/distress for moribund animals and tissue autolysis in dead animals.

4.2.3. Histology. The Contractor shall perform histology techniques including, but not limited to: trimming tissues into cassettes; processing tissues (dehydrating, clearing, and infiltrating); embedding tissues; sectioning blocks or frozen tissues; preparing slides; and staining slides. Each approved protocol shall dictate the parameters for tissue processing, embedding, and slide preparation. Some protocols shall require specialized techniques, including, but not limited to: non-immersion tissue fixation and special handling of tissues for Ribonucleic Acid (RNA) isolation.

4.2.4. Pathologist Services. The Contractor shall provide pathologists to monitor all necropsies, read slides and make diagnoses, and write pathology reports describing all pathological findings. Contractor pathologists shall be available to provide information on pathological findings during meetings (e.g. the TSSRC, QAS, PWG meetings).

4.2.5. Clinical Chemistry. The Contractor shall perform analyses (hematology and clinical chemistry) on blood samples and urinalysis as dictated by each approved protocol. Approved protocols shall require analyses of other samples including, but not limited to, spinal fluid, semen, vaginal smears, feces, amniotic fluid, synovial fluid, and bile. Hematology and clinical chemistry shall include, but not be limited to, blood cell counts, hemoglobin, hematocrit, platelets, cholesterol, triglycerides, blood urea nitrogen, creatinine, glucose, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, amylase, creatine kinase, calcium, inorganic phosphorus, sodium, potassium, and chloride. Urinalysis shall include, but not be limited to, urine volume, urine creatinine, protein, and urine glucose. Approved protocols shall require any number of additional analyses, which require enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA) or other assay methods.

4.2.6. Immunohistochemistry and Special Procedures. The Contractor shall perform immunohistochemistry (IHC) on slides as dictated by approved protocols. IHC targets shall include, but not be limited to, specific immune cell types (e.g., CD3, CD2, or CD21), cancer or other disease biomarkers (e.g., Ki-67or CK-7), and other specific proteins (e.g., glutathione or TdT).

Special Procedures may include, but not be limited to: embedding, sectioning, and staining tissues using plastics (resins); sectioning of frozen tissues; embedding, sectioning, and staining of whole zebrafish; preparation and staining of fetal cartilage and skeletons for teratologic examination; preparing and staining mammary whole mounts; and laser capture microdissection (LCMD).

The Contractor shall recycle waste ethanol, methanol, acetone, and xzylene to histological grade solvents suitable for routine pathology procedures, and shall recycle waste formalin to 10% Neutral Buffered Formalin suitable for routine fixation of tissues.

4.2.7. Molecular Pathology and Methods Development. The Contractor shall develop molecular pathology methods as required by approved protocols. The Contractor shall research techniques and reagents to best provide the analyses needed. Methods development shall involve, but not be limited to, IHC, LCMD, ELISA, and RIA.

4.2.8. Digital Imaging. The Contractor shall provide high quality digital images of gross specimens and high resolution digital images of glass slides as required by approved protocols. The Contractor shall provide analysis of these images as required by approved protocols. At the request of the PI, images shall be made available on a network server provided by the Government.

4.2.9. Data Management. The Contractor shall use the Government provided database systems (described below) to manage histopathology data associated with each animal on each protocol. Necropsy data, including, but not limited to, animal receipt, and body and organ weights, shall be entered into the GPS. GPS reports include Individual Animal Necropsy Reports (IANR), Protocol Definition reports, and IANR Lists. Pathologists’ readings of the slides shall be entered into either the Micropathology Data Collection System (MDCS or Micropath) or TDMSE (Toxicology Data Management System Enterprise; NTP protocols only). Micropath is the NCTR database system for collecting and maintaining histopathological data. Micropath shall be used primarily to collect histopathology observations and notes and to generate reports. TDMSE shall be used to collect, store, and report selected information produced from the in-life and histopathology portions of NTP studies. TDMSE is controlled by NTP.

GPS and Micropath are owned and maintained by NCTR and TDMSE is owned and maintained by NIEHS/NTP. The Contractor shall be responsible for ensuring proficiency in using GPS, Micropath, and TDMSE. User guides for GPS and Micropath are in Appendix 2. Contractors may obtain information about TDMSE from NTP.

The Contractor shall ensure that all information in the databases is up to date and maintain all study data relative to each animal on each protocol.

4.2.10. Archive Management (Wet Tissue and Block/Slide). The Contractor shall perform archiving services for all study (protocol) materials. The Contractor shall control access to archived study materials, provide a system to catalog materials, and track custody of materials that are “checked out” of the archive area by authorized personnel (authorized personnel would include Contractor staff with a need to use or examine the study materials and the PI or his/her designee).

4.2.11. Internal Quality Assurance. The Contractor shall provide Quality Assurance (QA) for the portion of each GLP protocol performed by the Contractor. This QA shall ensure that the processes followed by the Contractor for GLP studies are performed correctly and documented properly. In addition to internal QA auditing performed by the Contractor, the NCTR QAU shall periodically perform QA audits/inspections of the Contractor’s procedures and records pertaining to GLP studies. Pathology reports for GLP studies are subject to audit by NCTR’s QAU as a part of the review of the study reports.

4.2.11.1. As required by 21 CFR Part 58 (GLPs), 40 CFR Parts 160 and 792 (http://www.ecfr.gov/cgi-bin/text-idx?SID=c896b5fc9237c2649f2c84d5222c8d6a&node=40:33.0.1.1.3&rgn=div5), and the OECD Principles of Good Laboratory Practice, the Contractor’s QA shall:

4.2.11.1.1. Be independent of the personnel engaged in the conduct of the regulated study.

4.2.11.1.2. Monitor each regulated study to assure that the facilities, equipment, personnel, methods, practices, records, and controls used in completing their responsible functions for a regulated study are in conformance with the applicable regulations.

4.2.11.1.3. Maintain a copy of a master schedule sheet of all non-clinical laboratory studies conducted at the testing facility that require pathology support indexed by test article and containing the test system, nature of study, date study was initiated, current status of each study, identity of the sponsor, and name of the study director.

4.2.11.1.4. Maintain copies of all protocols (including applicable amendments/changes) pertaining to all regulated non-clinical laboratory studies for which the Contractor is responsible.

4.2.11.1.5. Inspect each regulated non-clinical laboratory study at intervals adequate to assure the integrity of the study, including periodic area assessments, phase inspections, data and report audits, and maintain written and properly signed records of each periodic audit/inspection showing the date of the audit/inspection, the study inspected, the phase or segment of the study inspected, the person performing the inspection, findings and problems, action recommended and taken to resolve existing problems, and any scheduled date for re-inspection. Audits/inspections shall include but not be limited to, periodic phase inspections, raw data (including support group worksheets), and report audits.

4.2.11.1.6. Provide results of QA audits/inspections conducted in support of regulated studies to the study director, Contractor management, NCTR management, the COR, and the NCTR QAU. Any problems which are likely to affect study integrity shall be documented and brought to the attention of the study director and Contractor management immediately.

4.2.11.1.7. Ensure that no deviations from approved protocols or standard operating procedures are made without proper authorization and documentation.

4.2.11.1.8. Review the contributing study report to assure that such report accurately describes the methods and standard operating procedures, and that the reported results accurately reflect the raw data of the non-clinical laboratory study.

4.2.11.1.9. Prepare and sign a Quality Assurance Statement for all GLP studies to be included with the contributing study report that shall specify the date(s) inspections were made and findings reported to NCTR management and to the study director.

4.2.11.1.10. Maintain the applicable responsibilities, procedures, records, and indexing method of the Contractor’s QA in writing. These items, including, but not limited to, inspection dates, study and phase or segment thereof, and the name of the individual performing the inspection, shall be made available for inspection to any designated representative of the FDA (for regulatory purposes), the NCTR QAU, the COR, and the study director.

4.2.11.1.11. Provide access as requested by a designated representative of the FDA (for regulatory purposes), the study director, the COR, or the NCTR QAU to the written procedures established for the inspection and certification from the Contractor’s General Manager that inspections are being implemented, performed, documented, and followed-up.

4.2.11.2. The Contractor shall provide a response to each non-compliance within two (2) weeks of the date of issue of the inspection findings from either the Contractor’s QA or NCTR QAU. This response shall indicate the corrective action taken and be distributed to the study director, Contractor management, NCTR management, the COR, and the NCTR QAU.

4.2.11.3. Chronic studies funded through the IAG with NIEHS/NTP require additional pathology analysis through a QAS and PWG. After the Contractor has prepared the draft Pathology Report, the QAS and the subsequent PWG will be performed.

For the QAS, the Contractor shall make available (check out/in from the respective archives and set up for review) blocks, wet tissues, and slides with all of the accompanying paperwork as requested by the reviewing pathologist(s) prior to each review date. The number of blocks, wet tissues, and slides examined will be dependent upon study parameters and will vary from study to study.

For the subsequent PWG, the Contractor shall make available (check out from the archive and set up for review) slides and/or digital images of slides as requested based on the QAS.

4.2.12. Quality Control. The Contractor shall provide all quality control for services performed under this contract, ensuring that the results produced are complete and accurate. The Quality Control program shall be designed to ensure that the Contractor is providing pathology services in compliance with established SOPs, approved protocols, and applicable GLP requirements. The Contractor shall write, implement, and enforce a Quality Control Plan (QCP), which shall be reviewed and approved by the CO. The Contractor’s final QCP shall be submitted within 30 calendar days of contract award. The QCP shall be designed to monitor all functions in pathology services to confirm that results are complete, accurate, and in compliance with established SOPs, approved protocols, and applicable GLP requirements.

4.2.13. Instructional Services. The Contractor shall participate in instructional activities upon request from the COR to include, but not be limited to direct instruction of graduate or undergraduate students on pathology topics and techniques, and leadership of workshop sections or informational meetings on pathology or related topics.

4.3. Qualifications. The Contractor shall provide qualified professional, technical, and administrative personnel to fulfill complete pathology services as outlined above. The Contractor shall provide a staff with all required certifications, education, and experience to complete the services.

4.4. Quality Assurance Surveillance Plan (QASP). The QASP (Appendix 3) will be used to measure, monitor and evaluate performance under this contract.

5. Government Furnished Property (GFP) and Services.

5.1. Facilities. The Government will provide utilities (electricity, gas, water, telephone, and internet access for Government supplied computers only) as required for successful performance of the contract. The Government will provide the following support services on-site as required for successful performance of the contract: library services, personal computer training, bulk document reproduction, mail services (delivery of incoming mail and pick-up of outgoing mail), shipping (UPS or FedEx) and receiving, recycling receptacles and pick-up, and equipment/instrument repair. All pathology services will be performed at Jefferson Laboratories, 3900 NCTR Road, Jefferson, Arkansas 72079. On-site facilities are located in building 5B and include approximately 23,740 square feet of office, laboratory, and storage space. Floor plans for the space are in Appendix 4. The space is roughly distributed as follows:

5.1.1. Offices – 19 offices with a total of 3,270 square feet of space.

5.1.2. Conference room – 513 square feet of space.

5.1.3. Copier/Supply/Mailroom – 106 square feet of space.

5.1.4. Multi-use space – 1,569 square feet of space.

5.1.5. Necropsy lab – 2,639 square feet of space.

5.1.6. Histology lab – 2,336 square feet of space.

5.1.7. Clinical Pathology lab – 654 square feet of space.

5.1.8. Immunology/Special Procedures labs – 2 rooms with a total of 558 square feet of space.

5.1.9. Special equipment rooms – 2 rooms with a total of 155 square feet of space.

5.1.10. Molecular and Special Techniques lab – 301 square feet of space.

5.1.11. Animal Holding rooms – 2 rooms with a total of 543 square feet of space.

5.1.12. Chemical room – 385 square feet of space.

5.1.13. Working Wet Tissue Archive (open studies) – 617 square feet of space.

5.1.14. Working Block/Slide Archive (open studies) – 549 square feet of space.

5.1.15. Long-term Wet Tissue Archive (completed studies) – 2 rooms with a total of approximately 1,352 square feet of space.

5.1.16. Long-term Block/Slide Archive (completed studies) – 3 rooms with a total of approximately 720 square feet of space.

5.1.17. Storage space – 11 rooms with a total of approximately 7,473 square feet of space.

The Contractor shall be responsible for the logistics involved in moving packages or supplies to various areas on the Jefferson Laboratories campus (e.g., packages to be shipped shall be taken to a shipping area, supplies shall occasionally be needed to perform pathology services in areas adjacent to or within animal facilities, etc.) using the transportation provided (i.e., a golf cart).

5.2. Equipment and Supplies.

5.2.1. The Government will provide all office equipment (e.g. desks, chairs, filing cabinets, phones, etc.) and office supplies (e.g. pens, paper, toner, etc.) directly required to provide the pathology services described herein. The Contractor shall recycle non-confidential documents whenever they are no longer needed.

5.2.2. The Government will provide computers (1) that are associated with laboratory equipment, (2) for use in laboratory areas (e.g., in the necropsy lab for entering data in GPS; in the histology lab for making labels for slides; etc.), (3) in the Data Management area, (3) in the archive areas, and (4) in the offices of Contractor administration, laboratory managers, and supervisors. Only Government-supplied computers may be connected to the FDA network. All Contractors with access to FDA computers shall complete annual computer security training to maintain computer access. The Government will provide all IT support for Government furnished computers. The Contractor shall turn off all computers that are not attached to laboratory equipment, or otherwise required to continue running, at the end of each week to conserve power.

5.2.3. The Government will provide all laboratory supplies (e.g. scalpels, scissors, pipettors, etc.) directly required to provide the services described herein.

5.2.4. Pursuant to the “Government Property” clause in, Section I of the solicitation, the equipment to be provided for use/operation by the Contractor is listed in Appendix 5.

5.2.5. The Contractor shall be fully responsible for loss, destruction, or damage resulting from willful negligence or lack of good faith of any of the Contractor’s personnel to maintain and administer the program for maintenance, repair, protection, and preservation of the property in accordance with the clause in Section I of the solicitation, entitled “Government Property”.

5.2.6. In addition to the applicable “Government Property” clause in Part II, Section I, the Contractor shall comply with the provisions of DHHS publication “HHS Contracting Guide for Contract of Government Property”, which is hereby incorporated by reference (http://ncioa.cancer.gov/oa-internet/reference/Appendix_Q_HHS_Contracting_Guide-508.pdf ).

Exceptions to information in the Guide:

5.2.6.1. The Sensitive Item List referred to in the Guide is replaced by the following list:

a. Central Processing Unit (CPU) Assemblies

b. Wireless equipment

c. Voice Recorder/Transcriber

d. Pagers

e. Facsimile Machines

f. Freezers

g. Gamma Counters

h. Geiger Counters

i. Incubators

j. Laser Disc Players

k. DVD Players

l. Laboratory Balances

m. Liquid Scintillation Counters

n. Microwave Ovens

o. Photographic Cameras and Lenses

p. Portable Gas Generators

q. Refrigerators

r. Scanners

s. Spectrophotometers

t. Televisions

u. Video Recorders

v. VCRs

w. Power Tools >$100

x. Microscopes

y. 2-Way Radios

z. Monitors

aa. Printers

ab. Copiers

ac. Weapons (including tranquilizer guns)

5.2.6.2. The Government shall provide all maintenance on GFP. The Contractor shall notify the COR immediately when any GFP requires unscheduled maintenance or repair.

5.2.7. The Government will provide all consumable materials and supplies required to directly perform the pathology services required for each protocol. The Contractor is responsible for maintaining, through purchase requests to the COR, a level of inventory of commonly used supplies (e.g. paraffin, gloves, slides, etc.) to meet workload demands.

6. REPORTING REQUIREMENTS/DELIVERABLES

6.1. Monthly Productivity Report. By the fifteenth (15th) of each month, the Contractor shall submit a productivity report describing all work performed during the previous month to the CO and COR. The report shall indicate the protocol numbers associated with the work. The report shall include all areas of work described in the PWS and include quantitative data for each area along with any applicable supporting data to completely explain the progress. This report shall include any tables, graphs, diagrams, sketches, photographs, or other descriptive figures necessary to completely explain the progress for the reporting period. The report shall contain descriptions of any new techniques or technology used; any problems that impeded performance and corrective action proposed or taken; work to be performed during the next reporting period; and personnel actions, including any meeting attendance or other notable information, including authorship on presentations and publications.

6.2. Annual Report. Within thirty (30) calendar days of completion of each period of performance, the Contractor shall submit a report (including a summary of the results of the contract work and all tables, graphs, diagrams, sketches, photographs, or other descriptive figures necessary to completely explain the results) for the contract year to the CO and COR. This report shall be complete and contain no reference, directly or indirectly, to other reports required under the contract. This report may also include descriptions of major accomplishments during the contract year.

6.3. Monthly Protocol Cost Tracking Reports. Protocol Labor and Materials/Supplies Report. Within fifteen (15) calendar days of the end of each month, the Contractor shall submit a report to include hours expended against each protocol during that month to the CO and the COR. This report shall also include the cost of Government-provided supplies used during that month for each protocol. IAG/CRADA Protocol Supply Cost Report. Within fifteen (15) calendar days of the end of each month, the Contractor shall submit a report to include the cost of all Government-provided materials and supplies expended against each IAG or CRADA project during that month to the NCTR Finance Office, the NTP IAG Program Manager, and the COR. This report shall include the Experiment number, agreement financial identification number, PI name, and total charge (monthly and cumulative within each fiscal year) for each protocol.

6.4. Quarterly Safety/Accident Report. The Contractor shall submit a Safety/Accident Report within fifteen (15) days of the end of each quarter to the CO and COR. The report shall include all accidents and incidents resulting in death, traumatic injury, occupational disease, and/or damage to all property incidental to work performed under the contract.

6.5. Pathology Reports. Pathology reports shall be written by Pathologists, explaining in detail the histopathological findings of each experiment (or portion thereof). Each experiment requiring pathology work will have an established time period following completion of the experiment (or a portion thereof) during which the draft summary of the pathological assessment of the experiment shall be submitted to the PI in charge of the study. In general, pathology reports for NTP studies shall be submitted to the PI within three (3) months of the final necropsy for 90-day studies and within six (6) months of the final necropsy for standard chronic studies. During periods of high-volume, these timeframes shall be negotiated with the PI and, for NTP studies, the Office of Scientific Coordination.

6.6. Biweekly Time Report. The Contractor shall enter time spent working on each protocol or support activity by Friday of the Government pay week (two week pay period) into NEAT, the Government’s system to track time spent on each approved protocol or other activity.

6.7. Safety Plan. Prior to commencement of work under the contract, the Contractor shall provide a Safety and Health Plan that is consistent with the OSHA Safety and Health Program Management Guidelines (which may be found at https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=FEDERAL_REGISTER&p_id=12909) and that is appropriate to the work to be performed under this contract. OSHA provides sample program plans at https://www.osha.gov/dcsp/compliance_assistance/sampleprograms.html, which may be used as guidelines in generating an appropriate Plan.