ATTACHMENT 1 STATEMENT OF WORK.pdf

Statement of Work Center for Devices and Radiological Health

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

1 BACKGROUND

2 OBJECTIVE

3 SCOPE

4 TASKS

4.1 TASK ONE: TASK MANAGEMENT

4.1.1 SUBMIT A PROJECT MANAGEMENT PLAN

4.1.2 PARTICIPATE IN KICK-OFF MEETING

4.1.3 SUBMIT A QUALITY ASSURANCE PROJECT PLAN

4.1.4 PREPARE MEETING MINUTES AS ASSIGNED

4.1.5 SUBMIT WEEKLY STATUS REPORTS

4.1.6 SUBMIT MONTHLY PROGRESS REPORTS

4.1.7 DEVELOP A COMMUNICATION MANAGEMENT PLAN

4.1.8 BI-WEEKLY TELECONFERENCES

4.2 TASK TWO: MAINTAIN MONTHLY WORK PRODUCTS AND CUSTOMER INTERACTIONS LOGS

4.3 TASK THREE: SUBMIT A PATIENT SAMPLE ACQUISITION PLAN

4.4 TASK FOUR: PRESENT AND DISCUSS – ASSESSMENT OF PATIENT TISSUES SAMPLES

4.5 TASK FIVE: DRAFT FINAL STUDY REPORT

4.6 TASK SIX: SUBMIT FINAL STUDY REPORT

5 DELIVERABLES

5.1 FORMAT OF DELIVERABLES

5.2 DELIVERABLES SUBMISSION PROCEDURE

5.3 SUMMARY OF DELIVERABLES

6 KEY PERSONNEL

7 CONTRACT TYPE

8 PLACE OF PERFORMANCE

9 GOVERNMENT FURNISHED INFORMATION (GFI)

10 GOVERNMENT FURNISHED EQUIPMENT (GFE)

11 PERIOD OF PERFORMANCE

12 COMPETITION

13 NON-DISCLOSURE AGREEMENT REQUIRED

14 GOVERNMENT CONTACTS

15 HOLIDAYS AND GOVERNMENT CLOSURES

16 SECTION 508 STANDARD REQUIREMENTS

17 SECURITY REQUIREMENTS

18 ATTACHMENTS ........................................................................................................... ERROR! BOOKMARK NOT DEFINED.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

1 BACKGROUND

The Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable, and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

The mission of the Center for Devices and Radiological Health (CDRH) is to protect and promote the public health. CDRH assures that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products. We provide consumers, patients, their caregivers, and providers with understandable and accessible science-based information about the products we oversee. We facilitate medical device innovation by advancing regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the U.S.

The Office of Science and Engineering Laboratories (OSEL) supports the CDRH’s mission of protecting and promoting public health. The OSEL undertakes the highest quality science to provide their customers with the best methods, tools and expertise to:

• Ensure readiness for emerging and innovative medical technologies

• Develop appropriate evaluation strategies and testing standards

• Create accessible and understandable public health information and

• Deliver timely and accurate decisions for products across their life cycle.

Within OSEL, the Division of Biology, Chemistry, and Materials Science (DBCMS) participates in the Center's mission of protecting and promoting public health by identifying and investigating issues related to the interaction between medical devices and the human body. The division accomplishes this through activities supporting the OSEL mission.

DBCMS focuses on device issues that involve:

• Analytical chemistry and electrochemistry

• Biocompatibility, toxicology, and biological risk assessment

• Biosensors and biomarkers

• Extractables, leachables, and chemical contamination

• Genomic and genetic technologies

• Immune and cellular responses

• Infection control, sterility, and biofilms

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

• Materials characterization, processing, and materials degradation

• Modeling of physiological processes

• Multicomponent mass transfer and reaction kinetics, and

• Nanotechnology.

This procurement shall fulfill FDA/CDRH’s strategic priority to investigate adverse health outcomes resulting from metal alloy implants.

As part of CDRH’s regulatory mission, we conduct surveillance to identify post-market signals that indicate there may be a concern with a medical device. Based on this surveillance, safety concerns associated with metal-containing implants were identified. The biocompatibility of metal-containing implants is metal-dependent, with some having the potential to cause more adverse outcomes-based patient genetic/genomics/comorbidities, location of implant, and/or metal alloy composition. These specific local and systemic tissue responses to metal exposure are also patient-dependent, indicating that meaningful data could be generated by examining patient biopsies/explants and local tissues to better identify associated biological traits to then forecast adverse outcomes, including patient immune responses.

For example, nickel-titanium alloys (NiTi) are commonly used in a variety of medical device implants ranging from cardiovascular stents to bone screws, though the microenvironments for these medical devices differ significantly. NiTi implants will undergo different physical and biochemical stresses which influence corrosion and subsequent metal-ion release, particularly nickel (Ni), thus location and local biology can determine cellular response and effect on tissue.

Nickel can be genotoxic and cytotoxic to both humans and animals, and though less common, carcinogenic. In murine models, Ni exposure is shown to induce chronic inflammatory events, elevate B-lymphocytes, and suppress humoral immune responses. In human patients, chronic lung Ni exposure is shown to impact gene expression of ~2700 differentially expressed genes and elevate CD4+ and CD8+ T cell responses in skin allergy models. Aside from direct exposure, many documented events of animal and human NiTi implants have shown Ni-release which correlated an increase in pro-inflammatory cytokines, indicative of implant rejection. Taken together, the location of NiTi medical device implantation is immunologically relevant and understudied.

In 2019, a working group was created and asked to summarize what was known and unknown about biological responses to metal-containing implants. From those unknowns, the group identified regulatory science research areas and projects that could address those knowledge gaps. One of the gaps identified was understanding the systemic and local immune responses related to metal-containing implants, with respect to the anatomical location of the implant.

Complementing this effort and important to this Statement of Work (SOW), little is known

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 about how patient-specific traits play a role in the allergic response to metal-containing implants. Therefore, clinicians and scientists lack the ability to predict adverse outcomes following device implantation. Due to these gaps in the field, it remains challenging to:

• Select patient-centric implant materials

• Forecast acute and chronic metal allergies, and

• Understand the immunologic relationship between the implant location, metal-type, relative to patients.

For this acquisition, the Contractor should be able to sequester patient samples appropriate to identify cellular dynamics using methods described (i.e. (epi)genomic sequencing, RNASeq, NanoString, or other ‘omics’-based platforms, immunohistochemistry, immunopathology, and/or other assay methods to identify the types of immune and cellular responses described, from adverse response to metal-alloys.

Potential Contractors with an existing library of samples, with a significant population of samples readily accessible for examination, and with a preexisting portfolio of markers are highly encouraged.

Proposals shall include detailed study plans that include relevant study periods for tissue examination with methods/protocols/analyses required for patient sample examination to a metal-containing device and detailed description of relevant techniques (such as flow cytometry markers, next generation sequencing, RNA seq, methylation array analysis, NanoString analysis, immunohistochemistry, immunocytochemistry, histology/pathology analysis, etc.).

These data will be used to predict potential adverse outcomes following metal-containing device implantation. CDRH will work with the contractor and, other collaborative teams the contractor may work with, to analyze high-throughput data to assess medical device/implant associations to safety signals.

CDRH will review data as well as study reports generated by the contractor and provide feedback.

Note: This effort is a continuation to an existing requirement, Contract Number:

75F40122C00188. The government requires external services as we do not house or actively collect human patient samples or data associated to samples from patients who experienced adverse outcomes resulting from metal alloy implants.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

2 OBJECTIVE

The objective of this acquisition is to understand how medical device implantation alters local and/or systemic immune response relative to implanted metal-alloy devices. This effort will utilize human patient samples to assess whether tissue/cellular responses-resulted in pathological immune and or cell activation with respect to metal-containing implants.

CDRH will solicit an external contractor for CDRH/OSEL/DBCMS that will meet important objectives:

1. To characterize patient tissues for immunological and cellular/molecular responses to metal-alloy implants and

2. Identify specific immune markers (i.e., cytokines/chemokines/interleukins, cell-receptors, immune cell subsets, etc. uniquely expressed from metal-alloy exposure.

The external contractor will design experiments which use “omics” and immunohistochemistry / immunocytochemistry / molecular pathology tools and other necessary methods / assays to monitor immune markers (described above) between host immune cells and surrounding implant tissue (bone, muscle, lymphatic tissues, epithelial, endothelial etc.).

3 SCOPE

The Contractor shall specifically acquire de-identified patient tissue samples explicit to those metal, implanted medical devices described in our SOW. These data should be from hospital systems, where access to clinical data and other patient data that are otherwise limited outside of not-for-profit medical/health sciences center hospitals.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation

4 TASKS

The Contractor and/or Consortium shall have suitable patient samples and reasonably significant populations of samples (statistically significant population) to assess immune, cellular and molecular markers resulting from adverse reactions to implantation with metal-alloy medical devices. The Contractor shall document a record of conducting examination of appropriately acquired and preserved patient samples for studies/evaluations, and employees assigned to this project should have extensive expertise in device associated analysis of tissue and immune response from metal-alloy implants, including those methods described with the tasks outlined below.

4.1 TASK ONE: TASK MANAGEMENT

The goal of the tasks in this section is to ensure efficient coordination, management, oversight, and reporting of activities conducted by the Contractor in support of CDRH and DBCMS.

Throughout this Order, the Contractor shall work with the FDA’s Contracting Officer Representative (COR), CDRH and DBCMS leadership, and assigned Technical Points of Contact (TPOCs) to provide technical and/or administrative assistance, and review and support services to ensure that the tasks are performed efficiently, accurately, on time, and in compliance with the requirements of this SOW.

Several approaches may be considered towards accomplishing the Task components in this document. Offerors are encouraged to consider approaches based on their facility/consortium capabilities to simplify workflow, manage study size, and eliminate biases.

To accomplish this, the Contractor shall complete the following tasks:

4.1.1 SUBMIT A PROJECT MANAGEMENT PLAN

Create a comprehensive Project Management Plan (PMP) regarding activities / deliverables to accomplish the tasks assigned by CDRH/DBCMS.

The PMP will include an implementation plan, task schedule, key milestones, and all deliverables with proposed due dates. The draft version of the Project Management Plan shall be submitted to the government for review within five (5) business days of the Kickoff Meeting.

CDRH/DBCMS shall review and request revisions, if needed, within ten (10) business days.

The PMP shall allow the Contractor to coordinate all activities and tasks with the CDRH COR, DBCMS leadership, and TPOCs to ensure that assigned tasks are prioritized and executed consistently in accordance with overall contract requirements.

Additionally, the Contractor should describe throughput capabilities, capability to ensure availability of patient tissue samples with appropriate quality to conduct described analyses, Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 management controls necessary to meet cost, schedule, and performance requirements.

Appropriate controls for delivery/source consistency should be detailed particularly if multiple institutions will work collaboratively to provide tissue samples and associated data, within performance of the task.

The PMP should also include Study Designs and Draft Protocols.

The Final Draft of the Project Management Plan is due within five (5) business days of receiving CDRH/DBCMS feedback.

4.1.2 PARTICIPATE IN KICK-OFF MEETING

Within ten (10) business days after contract award, participate in a Kick-Off Meeting with the CDRH COR, and DBCMS leadership, TPOC, and other staff as required. The Contractor shall prepare summary meeting minutes, detailing the discussion held, and provide a copy of the minutes to the COR within five (5) business days after the meeting.

4.1.3 SUBMIT A QUALITY ASSURANCE PROJECT PLAN

The Quality Assurance Project Plan should describe each study to be conducted under this Task Order and demonstrate how risks to data quality and integrity as identified by the Contractor will be mitigated by the Contractor’s quality systems. The draft version of the Quality Assurance Project Plan shall be submitted to the government for review within five (5) business days of the Kickoff Meeting. CDRH/DBCMS shall review and request revisions, if needed, within ten (10) business days.

4.1.4 PREPARE MEETING MINUTES AS ASSIGNED

The Contractor shall work with the COR, CDRH/DCBMS leadership TPOCs, and subject matter experts (SMEs) to ensure that tasks stay on track and important milestones are met. As tasked, participate in meetings for program and project planning, coordination, status, etc., and other Government meetings; prepare minutes for various initiatives that the Contractor shall support.

Upon request, meeting minutes will be submitted for FDA review and approval within five (5) business days of meeting completion.

4.1.5 SUBMIT MONTHLY STATUS REPORTS

The Contractor shall provide a brief Monthly Status Report as agreed upon with the COR to track the status of assigned tasks. This report shall include review of progress against all tasks, Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 identify resolve challenges and outstanding questions, identify accomplishments/issues for leadership attention/action. A Monthly Status Report will be submitted for FDA review and approval on dates agreed upon by FDA representatives and Contractor in the PMP.

4.1.6 SUBMIT MONTHLY PROGRESS REPORTS

The Contractor shall provide a Monthly Progress Report (MPR) that clearly outlines tasks/activities assigned and the personnel assigned to support each, to ensure that the expenditure of resources is in a manner that is consistent with, and will lead toward successful completion of, all tasks within projected cost and schedule limitations. MPR(s) shall detail progress made during the prior month, to contain at a minimum:

• Synopsis of assigned taskings

• Status of tasks

• Status of deliverables which will include activities and accomplishments, date due/delivered

• Milestones to ensure progression is measured

• Issues (to include any resource related issues) and expected resolution dates

• Risks and Mitigation approaches

• Planned activities for the next reporting period

• Open technical questions

• Requests for information and requests for documentation; and financial data to include current cost and level of efforts (e.g., hours worked for each personnel).

Invoices

The Contractor/Vendor shall ensure timely and accurate submission of monthly invoices that will track, at a minimum, the hours utilized each invoice period, total hours (dollars) used to date on the call order and remaining hours and funding under the call order. Monthly invoices will be attached to the MSR.

The Contractor/Vendor shall work with the COR, management, Executive Sponsor, and SMEs to ensure that tasks stay on track and important milestones are met.

Each MSR will be due no later than the fifth (5th) business day of each month.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

4.1.7 DEVELOP A COMMUNICATION MANAGEMENT PLAN

The Communication Management Plan shall outline’s communications goals and strategies for the task order. The Plan shall communicate the following with FDA-- experimental design, materials and methods, discuss patient specific samples to be sequestered for study (i.e., cardiac stents, orthopedic devices, or other clinically relevant implanted devices/ device types).

The Plan Template shall be provided by CDRH.

The draft version of the Communication Management Plan shall be submitted to the government for review on a date agreed to by both parties in the PMP. CDRH/DBCMS shall review and request revisions, if needed, within ten (10) business days.

4.1.8 BI-WEEKLY TELECONFERENCES

Periodic teleconferences (biweekly or as negotiated), draft agenda and supporting documents/data to be provided by Contractor at least 48 hours prior to teleconference.

Meeting minutes provided within 3 days after teleconference. Bi-Weekly Teleconferences will be held on a date agreed to by both parties in the PMP.

Note: All decisions regarding the implementation of any Contractor advice, guidance, and recommendations, shall be made by the FDA staff. In no case, will Contractor employees be empowered to make such decisions. The parties understand that Contractor services that would constitute inherently Government functions as described in FAR 7.5 are expressly prohibited.

4.2 TASK TWO: MAINTAIN MONTHLY WORK PRODUCTS AND CUSTOMER INTERACTIONS LOGS

The Contractor shall maintain logs of all work and customer interactions to be produced to the CDRH COR or designated Project Officer/Manager monthly. These logs shall be maintained on an CDRH shared drive. The Contractor shall demonstrate proficiency using Microsoft Office products, specifically, Excel, Word and PowerPoint. Monthly Logs will be submitted on a date agreed to by both parties in the PMP.

4.3 TASK THREE: SUBMIT A PATIENT SAMPLE ACQUISITION PLAN

Proposals should include a detailed plan for patient sample acquisition (methods to determine patient sample quality—including but not limited to sample preservation methods), corresponding assays for analysis, and approaches. Techniques used should facilitate patient sample assessment during study period and tissue/device assessment, as well as enable

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 examination of the involvement of both innate and adaptive immune responses. Contractors may propose additional assays relevant to the proposal. Data analysis should assess the same outcome indicators for each of the patient sample- device type pairings relative to their appropriate controls and extract any relevant findings that can be made across device types.

The Contractor shall expertly acquire and analyze data from these systems/platforms: we are expecting to obtain specific sets of exome sequencing data from targeted platforms unique to immune cell analysis, gene expression data from RNASeq platforms, histopathology data, immunohistochemistry and immunocytochemistry analysis, flow cytometry analysis of intracellular and extracellular surface receptors/marker expression, cytokine/chemokine analysis.

Draft Patient Sample Acquisition Plan is due no later than five (5) calendar days after Kickoff Meeting. CDRH/DBCMS shall review and request revisions, if needed, within ten (10) business days.

4.4 TASK FOUR: PRESENT AND DISCUSS – ASSESSMENT OF PATIENT TISSUES SAMPLES

Immune response related outcomes can be either beneficial or detrimental to the host. The immune system has been implicated as a contributor to adverse responses experienced following implantation of metal-containing devices. CDRH along with lead principal investigator/consortium will discuss the appropriate device(s) and surgical/anatomical location of explanted devices and/or biopsy tissues from patients (including number of available samples per a given device type/material) prior to study initiation.

Subtasks shall consist of the following:

FDA suggests assays pertinent to evaluation, including:

1. Exome sequencing of proximal and distal tissues from implant sight

2. Gene expression assays (or other ‘omics’-based assays to examine genomic/genetic modifications, other high throughput assays for examining immune/cellular/molecular responses

3. Histopathological examination, immunohistology/immunocytochemistry staining for immune cell subsets, cell receptor or immune expression factors and surface markers.

4. Additional assays that may address pertinent questions relative to implant are welcome by the solicitor/consortium for further review and evaluation by FDA.

5. Solicitors able to secure a cohort of patient samples that would be statistically significant based on study design with appropriate controls and experimental groups, from metal alloy devices that result in chronic immune response, especially orthopedic devices (i.e., knee arthroplasty), or some cardiac devices (i.e., Occluders etc.) and/or institutions with an

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 existing library of samples with candidate markers previously identified, are highly encouraged to apply for the solicitation.

6. ICPMS (Inductively Coupled Plasma Mass Spectrometry) analysis of patient tissue and rodent tissue samples taken from animal models selected to test anatomical location of metal alloy implants: Rodent samples could include tissues from multiple implant sites, with approximately 150 samples for testing. These samples are available to the vendor via previous research performed by Johns Hopkins University (JHU). Agreements for rodent tissue sample transfer may be required by the vendor and JHU. Data generated from the testing of the human samples will be provided to FDA. Data generated from the testing of the rodent samples will be provided to FDA and JHU. In all cases, data will be provided with the understanding that they may be used in manuscripts submitted for scientific peer review and publication in scientific journals, with mutually agreed-upon co-authorship.

Additional Considerations

The immunocompatibility of medical devices is dependent on their interaction with immune cells.

Relevant methods should be used to measure the composition of innate and adaptive immune cells (including B cell, T cell, macrophage, and their subsets) in relevant tissue compartments.

To monitor fibrotic tissue formation, fibroblast biomarkers (examples include: α-SMA, Collagen 1a1, Collagen 1a2 etc.), adhesion and inflammatory biomarkers should be analyzed in respect to tissue histopathology.

It is important to note that the bone marrow is essential for hematopoiesis and the origin of all immune cells. Metal particles released from orthopedic implant such as orthopedic screws will be considered as a key characteristic affecting proliferation and differentiation of hematopoietic stem cells (HSCs) and involved in lineage differentiations of HSCs in to lymphoid (T, B and NK cells) or myeloid (monocytes, macrophages neutrophils and other myeloblast cells) progenitor cells.

If tissue samples are of appropriate quality and allows for single-cell RNA expression analysis--cytokine profiling such as effector cytokine Granzyme B, IFN-γ, MIP-1α, TNF-α, TNF-β, stimulatory cytokine IL-5, chemoattractive cytokine MIP-1 β and regulatory cytokines IL-10, sCD137, sCD40L in T cell subsets or other immune cells, are valued. Comparable assays which would allow for these markers to be examined are welcome by the solicitor.

Studies must be well-controlled, with appropriate power tests conducted to enable discernment of statistically meaningful differences between experimental groups and

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 control(s). The contractor should emphasize identifying markers involved in adverse immune response following implantation with metal alloys. Studies should include the expression of genes encoding cytokines, chemokines, co-stimulatory molecules, major histocompatibility complex, immunosuppressors, immune regulators, pro-inflammatory mediators, those associated with innate and adaptive immune response.

The device types will be selected with direction from FDA staff based on medical device safety signals. Controls shall be blood or tissue samples from the same patient (matched) or patients with no adverse outcomes-- tissue samples deemed ‘non-disease’ or with normal histology compared with pathological tissue. Profiles in local tissue near the implant site will be evaluated to determine extent of tissue alteration by metal-containing device.

Contractor shall discuss and present preliminary results on a date agreed to in the PMP.

4.5 TASK FIVE: DRAFT FINAL STUDY REPORT

The Contractor shall submit a draft final study report for CDRH review and comment. The report shall summarize all work conducted during the period of performance of the TO and include tables with aggregated data and a narrative summary of the study results. For ‘omics’ data raw data files (SAM/BAM) files associated with genomic analyses (i.e., exome sequencing data and/or RNASeq analysis) should be provided along with analyzed data results and bioinformatic methods/tools used for (epi)genomic data analyses, including any version controls for sequencing platforms, software, or computational tools.

The Draft Final Study Report will be due on a date agreed to in the PMP.

4.6 TASK SIX: SUBMIT FINAL STUDY REPORT

The Report shall summarize all work conducted and provide all results specified in the study protocols. The Report shall summarize all study designs, draft protocols and draft reports for each subtask. Final protocols and study reports shall adequately address CDRH comments.

The Final Study Report shall address CDRH comments regarding the draft report.

The Final Study Report will be due on a date agreed to in the PMPs

SEND compatible data file (if applicable)

Note: This is a firm-fixed price effort for delivery of a complete research report. The contractor must deliver the completed report (which meets all requirements of the SOW) to satisfactorily complete the contract and receive payment.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

5 DELIVERABLES

Unless specified otherwise, CDRH will have ten (10) working days to complete the review and approve the deliverables. If deficiencies are found or areas require modification, the Contractor/Vendor will be notified and shall have five (5) calendar days to correct the deficiencies. Upon re-submission by the Contractor/Vendor, CDRH will reapply the same acceptance criteria. If the deliverable does not meet the acceptance criteria a second time, the CDRH may consider the Contractor/Vendor as having deficient performance with respect to the subject task.

Criteria for Acceptance:

The CDRH COR / designated Technical Point of Contact has the authority to accept or reject deliverables. The acceptance of deliverables and satisfactory work performance required herein shall be based upon the timeliness, accuracy and suitability of the deliverable. The specific deliverables and schedule for delivery shall be as agreed upon and documented.

Materials and resources shall be supplied by FDA, the Office of Science and Engineering Laboratories will supply the laboratory facilities, instruments, test items, and expendables necessary to perform the requirements under the terms of the contract. In addition, office space, computers, printing capability, telephone, and office supplies will be provided.

Summary of Consortium Responsibilities

The vendor shall manage the consortium: manage contact information of members, organize meetings, monitor tasks, share information and documents, keep a formal record, and act as the intermediary between members.

5.1 FORMAT OF DELIVERABLES

Deliverables (both in draft and final versions) shall be provided in hard and soft copy using MS Office products as specified below. Weekly, interim, informal, and working-copy products may be provided by e-mail to the COR or Technical POC. Final soft copies of deliverables shall be developed using the current FDA version of Microsoft Office products and/or other standard application software. Final hard copies of deliverables shall be typewritten on 8-1/2"x11" white paper. The Contractor shall not use spiral binding or other binding that interferes with photocopying.

5.2 DELIVERABLES SUBMISSION PROCEDURE

The Contractor shall submit all deliverables to the CDRH COR, unless otherwise stated. CDRH will be responsible for the review of all draft and final deliverables to ensure accuracy, Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 functionality, completeness, professional quality, and overall compliance with the guideline requirements of the task. The Contractor shall ensure the accuracy and completeness of all deliverables in accordance with referenced policy, regulations, laws, and directives.

Reports and presentations shall be concise and clearly written; errors, misleading or unclear statements, incomplete or irrelevant information, and/or excessive rhetoric, repetition, and "padding,” or excessive length if a page limit is imposed, shall be considered deficiencies and will be subject to correction by the Contractor at no additional cost to the government.

5.3 SUMMARY OF DELIVERABLES

Deliverables Table

Task(s) Deliverable (Recipients) Frequency/Due Date

4.1.1

Project Management Plan The PMP will include an implementation plan, task schedule, key milestones, and all deliverables with proposed due dates.

The PMP should also include:

• Throughput capabilities

• Capability to ensure availability of patient tissue samples with appropriate quality to conduct described analyses

• Appropriate controls for delivery/source consistency should be detailed particularly if multiple institutions will work collaboratively to provide tissue samples and associated data, Submit draft within 5 business days of Kickoff Meeting Final draft with 5 business days of receiving CDRH/OST feedback

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 within performance of the task.

The PMP should also include Study Designs and Draft Protocols.

4.1.2

Kickoff Meeting, including discussion of implementation plan, schedule, key milestones, and deliverables

Kickoff Meeting held within 10 calendar days of contract award

Meeting Minutes due 5 business days after meeting

4.1.3 Quality Assurance Project

Plan

NLT 5 calendar days after Kickoff Meeting

4.1.4 Various Meeting Minutes (As Assigned)

NLT 5 calendar days after assigned Meeting

4.1.5 Weekly Status Reports

Due on dates agreed upon in the PMP

4.1.6 Monthly Progress Reports Monthly Invoices shall be attached

NLT the fifth (5th) business day of each month

4.1.7

Communication Management Plan

Due date as agreed to in the

PMP

4.1.8 Bi-Weekly Teleconferences

Agenda and Minutes

Draft Agenda due NLT 2 days prior to meeting Meeting minutes due within 3 days after teleconference

4.2 Task Two—Monthly Work Products and Customer Interactions Logs

Due date as agreed to in the

PMP

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

4.3

Task Three –Patient Sample Acquisition Plan Patient Sample Acquisition- Location of Samples and Sample Types Plan should include:

Number of patient samples to be sequestered, surgical procedures, and device type from which biopsy and tissue samples will be acquired Data collection techniques:

histology, pathology, ‘omic’s based profiling experiments

Identifying Molecular Markers: Identify the genomic, genetic, or molecular markers involved in generating adverse outcomes in given patient samples

NLT 5 calendar days after Kickoff Meeting

First update / report to plan within 90 days after start of contract

Second update / report to plan within six (6) months after start of contract

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

4.4

Task Four – Discuss and Present Results on Data Analysis from Patient Samples Presentation shall include Data analysis and comparison of results from histology, pathology, immuno assays, and ‘omics’ platforms

4.5 Draft Final Study Report

4.6 Final Study Report

6 KEY PERSONNEL

The key personnel specified in this contract are considered to be essential to work performance.

Notification Before Diversion / Replacement

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to the Contractor/Vendor voluntarily diverting any of the specified individuals to other programs or contracts the Contractor/Vendor shall notify the Contracting Officer and shall submit a justification for the diversion or replacement and a request to replace the individual.

The request must identify the proposed replacement and provide an explanation of how the replacement's skills, experience, and credentials meet or exceed the requirements of the contract (including, when applicable, Human Subjects Testing requirements). If the employee of the Contractor/Vendor is terminated for cause or separates from the Contractor/Vendor

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 voluntarily with less than thirty days’ notice, the Contractor/Vendor shall provide the maximum notice practicable under the circumstances.

Written Consent Required

The Contractor/Vendor shall not divert, replace, or announce any such change to key personnel without the written consent of the Contracting Officer. The contract will be modified to add or delete key personnel as necessary to reflect the agreement of the parties.

Key Personnel and Skillsets

All work performed on this order will be performed with overview by the CDRH COR and Management and following FDA office guidelines. In addition to the description/experiences for scientists and researchers as outlined the following additional minimum skill sets required of the labor categories:

As previously described, investigators or consortiums with existing portfolio of markers that may require further development or additive biological insight from additionally patient samples are encouraged to participate as solicitors.

Investigators/consortiums with a statistically significant, developed library with patient samples preserved or with readily accessible content (and able to use high-throughput platforms for sample analysis) are highly encouraged as contributors to this solicitation.

All work performed on this effort will be conducted with overview by the CDRH COR and DBCMS. In addition to the description/experiences for clinical researchers as outlined in the base BPA the following additional minimum skill sets required of the labor categories are included below.

1. Principal Investigator/ Consortium Experts

Lead person on the research project and is responsible for the ethical and professional conduct of all aspects of the project

Minimum Qualifications

Requires a PhD (or equivalent) in a life sciences or engineering-related discipline, a minimum of 5 years related experience, and demonstrable technical expertise in projects related to this

SOW.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

2. Laboratory Technician

Prepares patient tissue samples, processing samples for genetic/genomic analysis, immunohisto or immunocyto chemistry methods, sample preparation for histology, microscopy, or other ‘omics’ based methods and sample preparation for ‘omics’ platforms.

Candidate would also maintain daily logs/basic records of methodologies and test results.

Minimum Qualifications:

Bachelor’s degree in the life sciences, biochemistry, bioengineering, chemical engineering or a related scientific field.

3. Graduate Student/Research Associate

Assist or contribute to methods, experimental design, or other laboratory work essential in securing patient samples and processing patient samples for analysis using efforts described for ‘laboratory technician’.

Candidate would also maintain daily logs/basic records of methodologies and test results

Minimum Qualifications:

Bachelor’s degree or recognized equivalent from an accredited institution; a satisfactory scholastic average, and satisfactory research training to do the proposed work.

All Personnel Required Skillsets

All personnel offered under this agreement shall have the following knowledge, skills and abilities:

The hires for the two positions (graduate student/research associate and laboratory technician) should have the ability to communicate orally and in writing. These two positions require the ability to understand and communicate scientific technical information. In addition to understanding the scientific aspects, these hires need to present the scientific data in a clear manner and at a level of understanding appropriate to the targeted audiences.

The principal investigator/consortium collaborators should have a contextual knowledge of immune responses in patients resulting from metal-alloy implants in the areas described regarding the study requirements and knowledge to conduct research using a variety of means (as described in the ‘background’ section of the SOW) for project ideas, development of collaborations to establish a consortium for appropriate patient sample acquisition, attainment and explanation of data to be transmitted in a logical understandable way or other types of documents for various audiences. The principal investigator will need that ability to review and

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 interpret patient samples/resulting examination of patient tissue samples, research data or ideas, presentation of those data in text, verbally, tables, and graphs, etc.…and develop logical discussion and conclusions as to what the data or information means. The principal investigator is responsible for providing monthly progress reports to FDA

Consortium Management

The Contractor shall manage the consortium including the contact information of members, organizing meetings, monitoring tasks, sharing information and documents. The Contractor shall keep a formal record of Consortium activities and act as the intermediary between members. The Contractor/Vendor shall ensure the accuracy and completeness of all deliverables in accordance with referenced policy, regulations, laws, and directives.

7 CONTRACT TYPE

The anticipated contract type is firm-fixed-price (FFP).

8 PLACE OF PERFORMANCE

Work may be accomplished at FDA White Oak Campus, contractor worksite, consortium/collaborator facilities, CORE facilities or a combination as approved by the CDRH

COR.

9 GOVERNMENT FURNISHED INFORMATION (GFI)

The FDA will provide the Contractor/Vendor with existing policy documentation via the COR.

The Government will retain all rights and privileges, including those of patent and copy, to all Government-furnished data and materials. (Covered by FAR/HHSAR, FDA Clauses) The Contractor/Vendor shall neither retain nor reproduce for private or commercial use any data or other materials furnished under this order. (Covered by clause) The Contractor/Vendor agrees not to assert any rights at common law or in equity or establish any claim to statutory copyright in such data. These rights are not exclusive and are beyond any other rights and remedies to which the Government is otherwise entitled elsewhere in this order. Moreover, at the conclusion of the contract (or as Acquisition projects are completed), the Contractor/Vendor shall ensure all data and information is appropriately returned to the COR.

All Contractor/Vendor staff working under this task order will be required to complete a Non-

Disclosure Agreement.

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023

10 GOVERNMENT FURNISHED EQUIPMENT (GFE)

There will be no government-furnished property.

11 PERIOD OF PERFORMANCE

For this continuation--the performance period will be 1 year (12 months), beginning on the date of contract award.

12 COMPETITION

X Full and Open/Fair Opportunity

☐ Justification for Other than Full and Open Competition/Limited Source Justification

☐ Brand Name or Equal (specific brand of product or equal to the listed brand)

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Patient Samples Impact of Medical Device Implantation

13 NON-DISCLOSURE AGREEMENT REQUIRED

The FDA will provide the Contractor/Vendor with existing policy documentation via the COR.

The Government will retain all rights and privileges, including those of patent and copy, to all Government-furnished data and materials. (Covered by FAR/HHSAR, FDA Clauses) The Contractor/Vendor shall neither retain nor reproduce for private or commercial use any data or other materials furnished under this order. (Covered by clause) The Contractor/Vendor agrees not to assert any rights at common law or in equity or establish any claim to statutory copyright in such data. These rights are not exclusive and are beyond any other rights and remedies to which the Government is otherwise entitled elsewhere in this order. Moreover, at the conclusion of the contract (or as Acquisition projects are completed), the Contractor/Vendor shall ensure all data and information is appropriately returned to the COR.

All Contractor/Vendor staff working under this task order will be required to complete a Non- Disclosure Agreement

The Government will provide FDA laptops to Contractor personnel performing work directly required by this contract. The Contractor shall maintain an inventory of all FDA accountable property and ensure the return of the property upon completion of all work required under this contract. Further, Contractor assigned to this order shall provide verification of completion of all mandatory FDA training, including Annual Security Awareness Training if assigned an FDA laptop that allows for FDA network access.

The Contractor is required to use government furnished property for all matters related to this contract, as required in Security Awareness training.

All property, data and information provided by the Government in the performance of this contract remains the property of the Government and shall be surrendered to the Government upon completion or termination of this requirement. Likewise, all deliverables generated under this requirement remain the property of the Government.

When the Government provides equipment, the Contractor shall maintain a detailed inventory accounting system for Government Furnished Property (GFP) following contract award. The inventory accounting system must specify, at a minimum:

• Product description (make, model)

• Government tag number

• Date of receipt

• Name of receipt

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Patient Samples Impact of Medical Device Implantation January 5, 2023

• Location of receipt

• Current location

• Contract/order number under which the equipment is being used

The Contractor shall attach an update inventory report to each MPR unless otherwise specified by the COR. In either case, the Contractor’s inventory listing must be available for Government review within one (1) business day of COR request. The Contractor shall remain responsible and accountable for all GFP for the duration of the contract and ensure the return of the property upon completion of all work required under this contract.

CDRH Property Custodian:

Name: Cedric Amey U.S. Food and Drug Administration White Oak Campus, Building 66 10903 New Hampshire Ave Silver Spring, MD 20993 Phone: 301-796-2306 Email: Cedric.Amey@fda.hhs.gov mailto:Cedric.Amey@fda.hhs.gov

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation

14 GOVERNMENT CONTACTS

Contracting Officer Representative (COR)

Susana Rosales Acquisition Program Specialist

FDA/CDRH/OM/DAS

WO66 RM5120

10903 New Hampshire Ave Silver Spring, MD 20993-0002 Tel: 301-796-2794 Email: Susana.Rosales@fda.hhs.gov

Technical Point of Contact (TPOC)

Program Manager Dr. Enusha Karunasena Microbiologist

FDA/CDRH/OSEL/DBCMS

WO64 RM4014

10903 New Hampshire Ave Silver Spring, MD 20993-0002 Tel: 240-402-5075 Email: Enusha.Karunasena@fda.hhs.gov mailto:Susana.Rosales@fda.hhs.gov mailto:Enusha.Karunasena@fda.hhs.gov

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Patient Samples Impact of Medical Device Implantation

15 HOLIDAYS AND GOVERNMENT CLOSURES

The Contractor is not required to provide on-site services on the following days that are Federal Holidays or on any other day designated as a Federal holiday, Government closure, or shut-down for the Washington, D.C. area:

New Year's Day

Martin Luther King Day

President 's Day

Memorial Day

Juneteenth

Independence Day

Labor Day

Columbus Day

Veteran 's Day

Thanksgiving Day

Christmas Day

Note: January 20, 2025 will be an additional Federal Holiday for the Inauguration. The Contractor shall not schedule training during federal holidays or Government closure. As necessary, training scheduled during unexpected Government closures may be rescheduled following coordination with the COR. The contractor shall not bill the Government for any training that the Contractor did not perform due to any Government closures.

16 SECTION 508 STANDARD REQUIREMENTS

Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d) requires Federal agencies to purchase information and communication technologies (ICT) that meet specific accessibility standards. This law helps to ensure that federal employees with disabilities have access to, and use of, the information and data they need to do their jobs. Furthermore, this law ensures that members of the public with disabilities have the ability to access government information and services.

There are three regulations addressing the requirements detailed in Section 508. The Section 508 technical and functional standards are codified at 36 CFR Part 1194 and may be accessed

Office of Science and Engineering Laboratories Division of Biology, Chemistry, and Materials Science

Patient Samples Impact of Medical Device Implantation January 5, 2023 through the Access Board’s Web site at http://www.access-board.gov. The second regulation issued to implement Section 508 is the Federal Acquisition Regulation (FAR). FAR Part 39.2 requires that agency acquisitions of Electronic and Information Technology (EIT) comply with the Access Board’s standards. The entire FAR is found at Chapter 1 of the Code of Federal Register (CFR) Title 48, located at http://www.acquisition.gov.