Attachment 1 Pathology PWS.pdf

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. NCTR is comprised of six research divisions and has facilities including: 132 general or special purpose research laboratories; an imaging center; a nanotechnology core facility; and an inhalation toxicology facility. NCTR has AAALAC-accredited animal facilities with animal housing accommodations including conventional housing for rodents, rabbits and large animal species (e.g. mini-swine), a rodent breeding colony, quarantine facilities for all species, and a zebrafish 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. Biosafety Level 2 (BSL2). BSL-2 labs are used to study moderate-risk agents that pose a danger if accidentally inhaled, swallowed, or exposed to the skin. Safety measures include the use of gloves and eyewear as well as handwashing sinks and waste decontamination facilities.

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

2.4. 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.

2.5. 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.

2.6. 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.

2.7. 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). Contractors may comment on the government’s evaluation and review their active performance and integrity information, which the government may use in making an award decision. To view this information, contractors must be registered in the CPARS system at https://www.cpars.gov/. CPARS training:

https://www.cpars.gov/webtrain.htm)

2.8. 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.

2.9. 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.

2.10. 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 (IAA). A document between government agencies and departments that defines cooperative work between the agencies. The IAA between FDA/NCTR and NIEHS/NTP has been in place since 1992. The IAA 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 Health Unit (OHU). The NCTR OHU provides physical exams, first aid, and assists in the treatment of occupational injuries or illnesses for all NCTR employees and residing contract employees.

2.16. 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 https://www.cpars.gov/ https://www.cpars.gov/webtrain.htm 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

2.17. Office of Scientific Coordination (OSC). The OSC mission is to “enable the research mission of NCTR and FDA by providing the support necessary for conducting in vivo toxicology studies”. The COR is part of this organization. The office of the NCTR Liaison to the CTP.

2.18. 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 (https://www.oecd.org/en/topics/sub-issues/testing-of-chemicals/test-guidelines.html).

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. 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.

2.21. Protocol. Protocols are experimental designs written by Principal Investigators, approved through NCTR management, and performed at NCTR

2.22. 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 (IQA).

2.23. Quality Management Team. Representatives from the Regulatory Compliance and Risk Management staff may conduct, for cause or voluntary audits, inspections and reviews to assess compliance with approved study protocols, established Standard Operating Procedures (SOPs) and demonstrated best data quality and integrity characteristics. Any observations are reported to the responsible laboratory personnel, study director, investigators, and management. Corrective action responses as a result of any observation include: protocol modifications; protocol/data/report/SOP clarifications and/or revisions; and protocol/SOP deviation documentation.

2.24. 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.

2.25. Regulatory Compliance and Risk Management (RCRM). RCRM is the office responsible for NCTR’s Safety, Security, Archives, OHU, and Quality Management.

Federal employees in this office conduct laboratory safety training and inspections, as well as QA inspections.

http://www.osha.gov/pls/oshaweb/owasrch.search_form?p_doc_type=STANDARDS&p_toc_level=0 http://www.osha.gov/pls/oshaweb/owasrch.search_form?p_doc_type=STANDARDS&p_toc_level=0

2.26. Restricted Areas. Special clearance procedures are required for access to the large animal facility. Access to the mini swine facility may be obtained when the following criteria are met: 1) legitimate need to enter the facility; 2) completion of NCTR safety and NCTR IACUC training; 3) annual flu vaccination and current enrollment in appropriate surveillance programs; and 4) approval from the Director of Veterinary Services. In addition, access to the rodent breeding colony and immunocompromised rodents is restricted so that no one may enter after previously having been in a conventional rodent facility on the same day. Personnel cannot enter the guinea pig area after entering/handling rabbit or mini swine areas. Personnel cannot enter rodent housing areas after handling rodents challenged with infectious agents. While in these areas, Contractor personnel are subject to applicable Jefferson Laboratories SOPs, which will be made available to those who are permitted access.

2.27. 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.

2.28. Study. A systematic investigation, including development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. All work is conducted according to an approved protocol and/or subsequent approved amendments (changes).

2.29. 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.

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

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) Appendix 6: AVMA Guidelines for the Euthanasia of Animals (PDF)

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 hundreds of 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. Some protocols may include requirements for histopathological processing, including immunohistochemistry, of human tissues or cells. Pathologists will not be expected to provide diagnoses for human tissues. 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 beyond 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.

Staff training should include cross training and other cost-saving efficiencies and value-added techniques.

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. The Government will not be responsible for any training required for job performance or to maintain required certification.

Occasionally the Government may require travel in support of NCTR specific comprehensive pathology services and technical procedures in accordance with the PWS.

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

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. Administrative Services and Management. The Contractor shall provide complete on-site project management and supervision to carry out all 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. Environment, Health, and Safety. The Contractor shall be responsible and qualified to handle all internal health and safety issues, including training staff, providing industrial hygiene services, and conducting safety inspections in the area occupied by the Contractor. The Contractor shall provide a point of contact to the COR upon appointment, and the qualified point of contact shall serve as the Contractor’s liaison to the Jefferson Laboratories Environment, Safety, and Health Committee.

4.2.2. 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 Quality Management Team for review.

Review of SOPs by the COR or NCTR’s Quality Management Team 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, up to a maximum of 90 days, at which time the new Contractor’s SOPs shall be in place.

4.2.3. Purchasing. The Contractor shall maintain a working stock of supplies and tools required for the performance of the work under this contract. As equipment becomes unreliable, breaks down, or is no longer supported by the manufacturer, 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 for confirmation that the equipment is necessary. For purchasing supplies and equipment, the Contractor shall follow the procedures below.

For credit card purchases, the Contractor shall gather pricing and vendor information and prepare an OSC purchase request form. The Contractor shall request purchase approval first by sending the form to the director of OSC, copying the COR and the OSC employee who will serve as the requestor for the purchase. After OSC approval, the Contractor shall enter a requisition in the Government’s procurement system, iProcurement. The Government will provide training for the use of iProcurement. When requisitions have been completely approved in 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. This process is expected to change during the period of performance for this contract. The government will provide training for any new processes that are required.

For purchases over $10,000 (or over the credit card limit at the time of purchase), the Contractor shall be responsible for the required documentation, which may include, but not be limited to, vendor quotes, a list of salient characteristics/requirements, and a justification of the need for the equipment or service. The COR will serve as the requestor for purchases over the credit card limit. The requisition approval process will remain the same as for credit card purchases, but the documentation and the purchase request will go to OAGS rather than to the COR/credit card holder.

The Contractor shall keep records of all documentation for all purchases, including all approvals, any quotes or pricing information, order confirmations (if available), invoices, packing slips, and any modifications to the requisition. The Contractor shall make these records available to the COR in a shared network folder. The Contractor shall reconcile the purchases for pathology on the monthly Government Purchase Card statement. The Contractor shall monitor the funding balance provided for pathology purchases in the DocView system (training for this system will be provided by the Government) 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 budget period.

4.2.4. Records/Audits. The Contractor shall maintain an accurate record of all

Government Furnished Property (GFP), including non-accountable property and accountable property. Accountable property shall be part of the annual Government inventory process. The Contractor shall provide the inventory record to the COR at least on an annual basis and shall provide a point of contact to participate in the Government inventory process. The Contractor is responsible for turn-in of obsolete and unused equipment.

During contract transition, the incumbent and incoming Contractors shall perform an inventory of GFP so that both parties agree on the inventory record upon transfer of responsibility.

4.2.5. Labor and cost estimates. 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 Planning and Resource Management (PRM). Prior to approval, concepts/protocols are distributed electronically to all support service areas for review, 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 concept/protocol from PRM 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 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 any portion of the approved protocol changes (including additions), resulting in a change (decrease/increase) in agreed upon cost or hours for pathology services. The Contractor is responsible for providing an amended cost estimate PRM, and copying the COR.

4.2.6. 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.

4.2.7. 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.

4.2.8. 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 6.3 below. The Government-supplied electronic tracking systems are described below. The Government will provide training for these systems. As the sole users of the Pathology Tracking system, pathology-related modules in the Pristima® system, and of some functions within the NCTR Experiment Activity Tracking system, the Contractor shall provide necessary user testing or feedback for any changes or upgrades to these systems, with approval from the COR.

4.2.9. 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.

4.2.10. 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. Path Track is an in-house system that will continue to be used by at least the molecular lab, even if a tracking system is provided in conjunction with Pristima® (see 4.2.9 Data Management).

4.2.11. Pristima®. NCTR has purchased Pristima to use as a pre-clinical data collection and management system to capture and report animal data from study setup to closure. NCTR has licensed Pristima with modules for Security, Animal Management, Clinical Pathology/Archive, Measurement Management, Tissue

Management, Lexicon Management, Study Management, Facility Management, System Utilities, Pharmacy, Reporting, Colony Management, Study Login, Animal Room, Necropsy, Pathology, Study Toolbox, Study Reporting, Non-Animal, and Savante. The Contractor shall use Pristima to set up the pathology portion of studies and to record pathology data for studies.

4.3. Gross Pathology. Necropsy activities will be in compliance with the approved protocol and any subsequently approved protocol changes..

The Contractor shall perform rodent, rabbit, and zebrafish necropsies in the Pathology facilities, unless otherwise directed in the protocol. BSL2 rodent necropsies will occur in building 62, room 175, unless otherwise directed in the protocol. The Contractor shall perform mini swine necropsies in the restricted large animal facility (see Section 2.27 regarding access to restricted areas). The Contractor shall provide “colony maintenance” (described below) for rodent, rabbit, and large animal facilities and the zebrafish facility.

4.3.1. 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: Guidelines for the euthanasia of animals | American Veterinary Medical Association (avma.org); Appendix 6) and with the approved protocol.

The Contractor shall perform euthanasia on study animals and any moribund animals that the attending veterinarian or PI 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 while under anesthesia, 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 will require anesthesia for blood collection prior to euthanasia.

4.3.2. 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: documentation of receipt of animals; documentation of animal weight; documentation of gross abnormalities or lesions; collection of any or all tissue and fluid samples (e.g. cerebrospinal, amniotic and synovial fluid); preparation of mammary gland whole mounts; vaginal cytology examinations for staging of estrus and confirmation of mating; bronchioalveolar lavage (BAL) for inhalation studies; preparation of specimens for conducting sperm morphometric analysis, motility assessment and sperm quantification; teratologic evaluation for https://www.avma.org/resources-tools/avma-policies/avma-guidelines-euthanasia-animals https://www.avma.org/resources-tools/avma-policies/avma-guidelines-euthanasia-animals developmental endpoints; corpora luteal counts; determination of uterine implantation and resorption sites; documentation of organ weight; photography of whole animals or lesions; perfusion of specific organs or whole animals; preparation and freezing of tissues; and 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.

4.3.3. 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, rabbit, large animal and zebrafish facilities 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.

4.4. 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 will require specialized techniques, including, but not limited to: non-immersion tissue fixation and special handling of tissues for ribonucleic acid (RNA) isolation.

4.5. 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.

4.6. Clinical Chemistry. The Contractor shall perform analyses (hematology, clinical chemistry and coagulation) 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 shall include, but not be limited to a complete blood cell count, with differential, packed cell volume (PCV), reticulocyte count, and staining for manual differential counts. Clinical chemistry shall include, but not be limited to, cholesterol, triglycerides, blood urea nitrogen, creatinine, glucose, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, amylase, creatine kinase, calcium, inorganic phosphorus, sodium, potassium, chloride, sorbitol dehydrogenase (SDH), total bile acids, quantitative urine creatinine, protein and glucose. Urinalysis shall include, but not be limited to, urine volume, specific gravity, pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin blood and microscopic analysis of the sediment.

Coagulation shall include, but not be limited to, protime, activated partial thromboplastin time (aPTT) and thrombin. Approved protocols will require any number of additional analyses, requiring enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA) or other assay methods.

4.7. Immunohistochemistry and Special Procedures. The Contractor shall perform immunohistochemistry (IHC) on slides as dictated by approved protocols. IHC targets may 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; post fixation osmification of tissues for demonstration of lipids in paraffin embedded tissue sections; EDTA decalcification of bone allowing for immunohistochemical staining; fixation, embedding and sectioning of human airway air-liquid interface (ALI) tissue cultures and rat testicular organoid from PND fetus.

The Contractor shall recycle waste ethanol, methanol, acetone, and xylene 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.

4.8. 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, ELISA, and RIA.

4.9. 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 digital images shall be archived and maintained in an accessible database system. 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.

4.10. Data Management. The Contractor shall use the Government-provided database systems (described below) to manage histopathology data associated with each animal on each protocol. During the performance of this contract, the government will transition from systems developed in-house for gross pathology and histopathological data management to Pristima® from Xybion. During this transition, both systems will be in use. Each study must be completed using the system in which it began.

Necropsy data, including, but not limited to, animal receipt, and body and organ weights, shall be entered into GPS. Pathologists’ readings of the slides shall be entered into the Micropathology Data Collection System (Micropath). 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. When the Government has completed the validation of Pristima®, pathology data for studies using it will be entered into the appropriate modules in that system.

GPS and Micropath are owned and maintained by NCTR. The Contractor shall be responsible for ensuring proficiency in using GPS and Micropath. User guides for GPS and Micropath are in Appendix 2. As the sole users of GPS and Micropath, the Contractor shall provide necessary user testing or feedback for any changes or upgrades to these systems, with approval from the COR.

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.

4.11. Archive Management (Wet Tissue and Block/Slide). The Contractor shall perform archiving services for all pathology-related study (protocol) materials. The Contractor shall control access to archived study materials, use the archive function in the Clinical Pathology module of Pristima® 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 their designee).

4.12. Internal Quality Assurance. The Contractor shall provide Internal Quality Assurance (IQA) for the portion of each protocol performed by the Contractor. The IQA Manager shall ensure that the processes followed by the Contractor for studies are performed according to approved protocols, amendments, applicable SOPs and best data quality and integrity practices. In addition to IQA auditing performed by the Contractor, the NCTR Quality Management Team may periodically perform audits/inspections of the Contractor’s procedures and records to assess the performance and integrity of the IQA activities. Pathology work is subject to audit by NCTR’s Quality Management Team as a part of the review of the study final reports.

The Contractor’s IQA Manager shall:

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

b. Monitor each study to assure that the facilities, equipment, personnel, methods, practices, records, and controls used in completing their responsible functions for a study are performed according to approved protocols, amendments, applicable SOPs, and best data quality and integrity practices.

c. Maintain access to an organizational/status tracking system of all studies conducted at the testing facility that require pathology support indexed by a system to include test article, test system, nature of study, date study was initiated, current status of each study, and name of the study director/principal investigator.

d. Maintain copies of all protocols (including applicable amendments/changes) pertaining to all studies for which the Contractor is responsible.

e. Inspect each study for which the Contractor is responsible at intervals adequate to assure the integrity of the study, including periodic area assessments, phase/process 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/process 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. Where appropriate, process inspections of shared study processes may be conducted periodically for each study.

f. Provide results of IQA audits/inspections to the study director, Contractor management, NCTR management, the COR, and the NCTR Quality Management Team. 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.

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

h. If requested, prepare, and sign a Quality Assurance Statement or equivalent for all 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.

i. Maintain the applicable responsibilities, procedures, records, and indexing method of the Contractor’s IQA 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, the NCTR Quality Management Team, the COR, and the study director.

j. Provide access as requested by a designated representative of the FDA, the study director, the COR, or the NCTR Quality Management Team 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.

k. 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 IQA or NCTR Quality Management Team. This response shall indicate the corrective action taken and be distributed to the study director, Contractor management, NCTR management, the COR, and the NCTR Quality Management Team.

4.13. 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, and approved protocols. 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 best data quality and integrity practices.

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

4.15. 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.

4.16. 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 as required for successful performance of the contract: personal computer training, 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 maintenance and 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:

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

• Conference room – 513 square feet of space.

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

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

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

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

• Clinical Pathology lab – 654 square feet of space.

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

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

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

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

• Chemical room – 385 square feet of space.

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

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

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

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

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

The Government plans to renovate building 5D for new onsite pathology facilities. The new facilities are expected to be available for occupation sometime in the last two years of this contract. The new facilities will occupy approximately 32,000 square feet. The floor plan for the new facilities is included in Appendix 4.

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, (4) in the archive areas, and (5) 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.

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 (google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGA xVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdef ault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2 520of%2520Government%2520Property- Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449).

The Sensitive Item List includes:

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 https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGAxVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdefault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2520of%2520Government%2520Property-Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449 https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGAxVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdefault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2520of%2520Government%2520Property-Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449 https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGAxVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdefault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2520of%2520Government%2520Property-Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449 https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGAxVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdefault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2520of%2520Government%2520Property-Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449 https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjdjLbumqSGAxVqNlkFHai9BdYQFnoECAYQAQ&url=https%3A%2F%2Foamp.od.nih.gov%2Fsites%2Fdefault%2Ffiles%2FDGS%2FHHS%2520Contracting%2520Guide%2520for%2520Contract%2520of%2520Government%2520Property-Appendix%2520Q.pdf&usg=AOvVaw1BrzPzjMdhkrCTIdMgNNrK&opi=89978449

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

bb. Copiers

cc. Weapons (including tranquilizer guns)

The Government will 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 any meeting attendance or other notable information, such as 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,…