FDA-RFP-2020-1229392 Impact of Anatomical Location on Device-Related Immune Responses.doc

Food and Drug Administration (FDA) file_0.png file_1.wmf

Notice Type: RFQ: Combined Synopsis/Solicitation

Subject: Request for Quotes: FDA-RFP-2020-1229392 Impact of Anatomical Location on Device-Related Immune Responses.

Section 1 - General This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation. Quotes are being requested and a written solicitation will not be issued.

Solicitation Number # FDA-RFP-2020-1229392: is being issued as a Request for Quotations (RFQ). The solicitation and incorporated provisions and clauses are those in effect through Federal Acquisition Circular FAC 2019-01. This requirement is being solicited under full and open competition using the Simplified Acquisition Procedures per FAR Subpart 13.5.

The associated NAICS Code is: 621111 Orthopedic physicians' offices (e.g., centers, clinics).

Section 2 - Contract Type The Government intends to award a Firm Fixed-Price (FFP) Contract, to procure the requested services for the Impact of Anatomical Location on Device-Related Immune Responses.

Section 3 - Description/Specifications and Work Statement.

3.1. Background

The mission of the Center for Devices and Radiological Health (CDRH) is to protect and promote the public health. CDRH ensures that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products. FDA provides consumers, patients, their caregivers, and providers with understandable and accessible science-based information about the products CDRH oversees. CDRH facilitates 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.

As part of its regulatory mission, CDRH conducts post-market surveillance to identify signals that indicate there may be a concern with a medical device. Based on this surveillance, safety concerns associated with metal-containing implants, particularly those used in the fields of orthopedics and gynecology were identified. 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 such knowledge gaps. One of the gaps identified was understanding of systemic and local immune responses to metal-containing implants. Specific local-tissue responses likely depend on the device or biomaterial and peri-implant tissue type, as well as patient-related characteristics. Systemic responses likely depend on device or biomaterial and patient-related characteristics as well.

The intent of this contract is to allow CDRH to have external Contractor support to more thoroughly investigate the role of device/implant location and the immune response experienced by an implant recipient, to gain enhanced understanding that can inform the regulatory approach CDRH employs regarding metal-containing devices. Also, this study will provide insight into device design/characteristics that may impact local and systemic immune responses. CDRH will work with the Contractor to identify up to three initial implant type/locations for study based on medical-device safety signals and animal-model logistics. These implant types will be drawn from common device areas, such as cardiovascular, gynecologic, and orthopedics.

3.2. Objective

The objective of this acquisition is to address how differences between metal-containing devices and contacting tissues (e.g., mucosal-contacting, endothelial-contacting, etc.) impact the innate and adaptive immune responses. This effort will utilize in vivo models to assess whether innate and adaptive immune responses vary across anatomical locations and with device type/characteristics. With respect to metal-containing implants, the results of this effort could:

enable better prediction of tissue-specific adverse reactions post implantation, and provide knowledge needed to potentially mitigate tissue-specific adverse reactions post implantation.

The Contractor will provide a final study report at project completion.

3.3. Scope.

The Contractor shall have a large-animal model (species to be determined) suitable for assessing the interaction between an implant’s location and its device type/characteristics. The Contractor shall include comprehensive study plans that include relevant in-life study periods that simulate chronic exposure to a metal-containing device and outline histopathological and immunological assessments. They should not include clinical assessment studies.

CDRH will review the data and the study report generated by the Contractor and provide feedback. The information gathered by the Contractor will be used to inform other CDRH efforts and policy positions regarding metal-containing devices.

3.4. Tasks

3.4.1. Task 1: Assess Immunological Response, Local and Systemic, to a Metal-Containing Device Implanted at Different Anatomical Locations.

The Contractor shall conduct a study of the immunological response, local and systemic, to a metal-containing device implanted at different anatomical locations. The immune system has been implicated as a contributor to adverse responses experienced following implantation of metal-containing devices. CDRH will select three approved implantable medical devices that contain metal, each with different mechanisms of action based on positive safety profiles, formulation, and route of delivery. The devices shall include a cardiovascular device, such as a stent; a gynecologic device, such as a Filshie clip; and an orthopedic device, such as a screw. Study designs, draft protocols, and draft reports for each subtask shall be provided for CDRH review and comment.

Task 1 shall consist of the following:

3.4.1.1. Task 1 (a) One CDRH-selected gynecologic device (e.g., Filshie clips), tested in three separate locations: intended use, subcutaneous, and control (sham surgery);

3.4.1.2. Task 1 (b) One CDRH-selected cardiovascular device (e.g., stent) tested in three separate locations: intended use, subcutaneous, and control (sham surgery);

3.4.1.3. Task 1 (c) One CDRH-selected orthopedic device (e.g., screw), tested in three separate locations: intended use, subcutaneous, and control (sham surgery).

The Contractor shall conduct studies that are well-controlled, blinded, and appropriately powered to enable discernment of statistically meaningful differences in immunological response, compared to control group(s). Studies shall assess innate and adaptive immunological response indicators across various anatomical locations and device types, relative to appropriate control groups. The anatomical location and device types shall be selected with direction from FDA staff, based on medical-device safety signals and animal-model logistics. Controls shall be surgeries where an implant is not placed but the same anatomical site is accessed and perturbed. The duration of the study’s in-life phase shall be based on chronic exposure in the selected animal model. The Contractor shall provide a plan to ensure appropriate blinding.

Also, the Contractor shall include plans to monitor potential indicators of adverse outcomes, including but not limited to: complete blood counts (CBCs), experimental observations, inflammation, osteolysis, and pseudotumor formation. Techniques used shall facilitate animal assessment during study period and tissue/device assessment at conclusion of study period, as well as examination of the involvement of both innate and adaptive immune responses. Post-experimental analysis of local tissue near the implant site shall be evaluated to determine the extent of tissue damage (fibrosis, necrosis, etc.) due to the placement of the metal-containing device. Contractors may propose additional assays relevant to immune response.

Additional tests shall be proposed to assess adverse tissue responses within each animal (i.e., osteolysis, necrosis, fibrosis, leukocyte infiltration, pseudotumor formation, etc.). Euthanasia at the agreed upon study endpoint shall be conducted to allow appropriate histopathological assessment near the implant location, as well as systemically. Data analysis shall assess the same outcome indicators for each of the anatomical location device-type pairings relative to their appropriate controls, also extract relevant findings that can be made across device types.

NOTE:

This project is focused on the task of gathering information on the anatomical and device characteristics that impact any immunologically-influenced adverse response to metal-containing implants.

Several approaches may be considered to accomplish the Task components in this document. The Contractor is encouraged to consider approaches based on their facility’s capabilities to simplify workflow, manage study size, and eliminate biases.

3.4.2. Task 2: Task/project management

3.4.2.1. Kickoff Meeting

The Contractor shall contact the COR and schedule a kickoff meeting within 5 workdays after the date of contract award. The Contractor shall include all Contractor Key Personnel considered critical to performance of the contract. During the meeting the Contractor shall provide a draft milestone schedule outlining planned actions for successful performance of the contract. The final milestone schedule shall be included in the project management plan. The Contractor shall take notes during the kickoff meeting and provide meeting minutes to the COR within 3 workdays following the kickoff meeting.

3.4.2.2. Periodic Teleconferences (biweekly, or as negotiated) The Contractor shall schedule and host a teleconference with CDRH/OSEL on a bi-weekly schedule, or as agreed to between the Contractor and the COR.

3.4.2.3. Project management plan

3.4.2.3.1. Project Management Plan (PMP)

The Project Management Plan shall address progress/status reporting, centralized functions, and integration with task-order activities. Additionally, the Contractor should describe throughput capabilities; the capability to ensure appropriate blinding of the veterinary care staff; and the management controls necessary to meet cost, schedule, and performance requirements. Also, appropriate controls for animal delivery/source consistency shall be detailed, especially if more than one animal order is anticipated within the performance of the task. The PMP shall be submitted to the COR within 1-month, from the date of contract award.

3.4.2.3.2. Communications Management Plan

The Contractor shall provide a communications management plan as part of the PMP. The plan shall outline the contract communications goals and strategies, using a template provided by CDRH.

3.4.2.3.3. Quality Assurance Project Plan

The Quality Assurance Project Plan shall be included with the PMP and shall cover each study conducted under this Task and demonstrate how risks to data quality and integrity, as identified by the Contractor, will be mitigated by the Contractor’s quality systems. *(Send compatible data files, if applicable)

3.4.2.4. Monthly Status Reporting

The Contractor shall conduct project management of all tasks to assure the completion of all tasks and the quality of performance and deliverable. The Contractor shall provide the COR status report to outline the progress of the project each month. The reports shall:

Describe progress in meeting the contract milestones, broken out by subtasks within each milestone, overall project assessment of data collected to date, and problems encountered (with recommended solutions);

Detail the planned progress and actual progress during the period covered, explaining occurrences of any differences and corrective steps/actions planned, if behind schedule;

Detail estimated and actual expenses, including a narrative of whether there are discrepancies between the percentage of work completed and the cumulative costs incurred to date. Also, this section of the report shall contain estimates for the subcontractors’ expenses from the previous month, if the subcontractor did not submit a bill in the previous month. If the subcontractor was not working or did not incur any costs in the previous month, then a statement to this effect shall be included.

Include an updated Gantt chart; and Include a three-month rolling forecast of key planned activities, referencing the project’s Work Breakdown Structure (WBS), as provided in the project management plan.

3.4.2.5 Summary Report of Study and Results

The reports shall summarize all the work conducted and provide all the results specified in the study protocol. Final protocols and study reports shall adequately address CDRH comments.

3.4.2.5.1. Draft Summary Report

A draft of the Final Study Report shall be provided to CDRH for review and comment. It shall summarize all work conducted during performance of the tasks and include tables with aggregated data and a narrative summary of the study results.

3.4.2.5.2. Final Summary Report

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

Deliverables 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. Final soft copies of deliverables shall be developed using the current FDA version of Microsoft Office products (Microsoft Offices 365 pro plus) 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.

Deliverables Submission Procedure

The Contractor shall submit all deliverables to the COR, unless otherwise stated. The COR will be responsible for the review of all draft and final deliverables to ensure accuracy, 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. Unless specified otherwise, the Government shall have ten (10) working days to complete the review and approve the deliverables. If deficiencies are found or areas require modification, the Contractor will be notified and shall have five (5) calendar days to correct the deficiencies. Upon re-submission by the Contractor, the Government will reapply the same acceptance criteria. If the deliverable does not meet the acceptance criteria a second time, the Government may consider the Contractor as having deficient performance with respect to the subject task.

Table of Deliverables

SOW Reference Description Media Due Date

4.1 *Study design and draft protocols Electronic/paper 1 month from date of contract award

4.1 *Surgical procedures and recovery pilot Electronic/lab notebook 3 months from date of contract award

4.1.1 Data collection and analysis for anatomical and immune response to gynecologic device

10 months from date of contract award

4.1.2 Data collection and analysis for anatomical and immune response to cardiovascular device

4.1.3 Data collection and analysis for anatomical and immune response to orthopedic device

4.1 *Data analysis across implant type/location Electronic 11 months from date of contract award

4.2.1 Draft milestone schedule

Submitted prior to start of the kickoff meeting

4.2.1 Kickoff meeting minutes

Within 3 workdays following the kickoff meeting

4.2.3 Project Management Plan Electronic/paper 1-month from date of contract award

4.2.4 Monthly Status Reports

The 15th workdays* of each month, beginning on the date of award

4.2.5.1 Draft Summary Report

No later than 40 workdays* prior to contract end date.

4.2.5.2 Final Summary Report Electronic No later than 20 workdays* prior to contract end date.

*Indicates an overarching component that is relevant to all subtasks NOTE: Workdays are Mondays – Fridays, excluding Government holidays or days the Government or FDA is shut down.

Special Material Requirements The Contractor shall be responsible for procuring the metal-containing implants to be used in the study, with input from CDRH staff on the appropriateness of the selected iteration of the device.

Place of Performance Performance will be at the Contractor’s and/or subcontractor’s facility. As required by the COR, the Contractor may need to make visits to Building 66, FDA White Oak Campus, Silver Spring, MD, for status updates.

PAYMENT SCHEDULE.

The Contractor shall submit monthly invoices, documenting the tasks/work accomplished during the period under consideration. For invoicing procedures, see the FDA Invoice Submission Instructions provided later.

Criteria for Acceptance/Surveillance

The FDA TPOC or designee 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 COR will monitor the Contractor’s performance by reviewing Monthly Status Reports and attending teleconference meetings.

Packing, Marking, Delivery and Shipping:

At a minimum, all deliverables shall be marked with the contract number and the Contractor’s name and delivered at the U. S. Food and Drug Administration (FDA) facility address listed below:

The U. S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) Research Materials Engineer Division of Biology, Chemistry, and Materials Science (DBCMS) Office of Science and Engineering Laboratories (OSEL) 10903 New Hampshire Ave, WO64 Rm 4076, Silver Spring, MD 20993

Period of Performance

Performance of this contract shall begin on 9/15/2020 THRU 9/14/2021 (One Year) 12 Months.

CLIN

Description Period of Performance Qty Impact of Anatomical Location on Device-Related Immune Responses

9/15/2020 THRU 9/14/2021

A. Baseline Security Requirements

1) Applicability. The requirements herein apply whether the entire contract or order (hereafter “contract”), or portion thereof, includes either or both of the following:

2) Safeguarding Information and Information Systems. In accordance with the Federal Information Processing Standards Publication (FIPS)199, Standards for Security Categorization of Federal Information and Information Systems, the Contractor (and/or any subcontractor) shall:

a. Protect government information and information systems in order to ensure:

b. Provide security for any Contractor systems, and information contained therein, connected to an FDA network or operated by the Contractor on behalf of FDA regardless of location. In addition, if new or unanticipated threats or hazards are discovered by either the agency or Contractor, or if existing safeguards have ceased to function, the discoverer shall immediately, within one (1) hour or less, bring the situation to the attention of the other party. This includes notifying the FDA Systems Management Center (SMC) within one (1) hour of discovery/detection in the event of an information security incident.

c. Adopt and implement the policies, procedures, controls, and standards required by the HHS/FDA Information Security Program to ensure the confidentiality, integrity, and availability of government information and government information systems for which the Contractor is responsible under this contract or to which the Contractor may otherwise have access under this contract. Obtain the FDA Information Security Program security requirements, outlined in the FDA Information Security and Privacy Policy (IS2P), by contacting the CO/COR or emailing your ISSO.

d. Comply with the Privacy Act requirements and tailor FAR clauses as needed.

3) Information Security Categorization. In accordance with FIPS 199 and National Institute of Standards and Technology (NIST) Special Publication (SP) 800-60, Volume II: Appendices to Guide for Mapping Types of Information and Information Systems to Security Categories, Appendix C, and based on information provided by the ISSO or other security representative, the risk level for each Security Objective and the Overall Risk Level, which is the highest watermark of the three factors (Confidentiality, Integrity, and Availability) of the information or information system are the following:

Based on information provided by the Privacy Office, system/data owner, or other privacy representative, it has been determined that this solicitation OR contract involves:

[X ] No PII [ ] Yes PII Personally-Identifiable Information (PII). Per the OMB Circular A-130, “PII is information that can be used to distinguish or trace an individual's identity, either alone or when combined with other information that is linked or linkable to a specific individual.” Examples of PII include, but are not limited to the following: Social Security number, date and place of birth, mother’s maiden name, biometric records, etc.

PII Confidentiality Impact Level has been determined to be: [X] Low [ ] Moderate [ ] High

4) Controlled Unclassified Information (CUI). CUI is defined as “information that laws, regulations, or Government-wide policies require to have safeguarding or dissemination controls, excluding classified information.” The Contractor (and/or any subcontractor) must comply with Executive Order 13556, Controlled Unclassified Information, (implemented at 3 CFR, part 2002) when handling CUI. 32 C.F.R. 2002.4(aa). As implemented the term “handling” refers to “…any use of CUI, including but not limited to marking, safeguarding, transporting, disseminating, re-using, and disposing of the information.” 81 Fed. Reg. 63323. All sensitive information that has been identified as CUI by a regulation or statute, handled by this solicitation/contract, shall be:

marked appropriately;

disclosed to authorized personnel on a Need-To-Know basis;

protected in accordance with NIST SP 800-53, Security and Privacy Controls for Federal Information Systems and Organizations applicable baseline if handled by a Contractor system operated on behalf of the agency, or NIST SP 800-171, Protecting Controlled Unclassified Information in Nonfederal Information Systems and Organizations if handled by internal Contractor system; and returned to FDA control, destroyed when no longer needed, or held until otherwise directed. Destruction of information and/or data shall be accomplished in accordance with NIST SP 800-88, Guidelines for Media Sanitization and the FDA IS2P Appendix T: Sanitization of Computer-Related Storage Media.

5) Protection of Sensitive Information. For security purposes, information is or may be sensitive because it requires security to protect its confidentiality, integrity, and/or availability. The Contractor (and/or any subcontractor) shall protect all government information that is or may be sensitive in accordance with OMB Memorandum M-06-16, Protection of Sensitive Agency Information by securing it with a FIPS 140-2 validated solution.

Confidentiality and Nondisclosure of Information. Any information provided to the Contractor (and/or any subcontractor) by FDA or collected by the Contractor on behalf of FDA shall be used only for the purpose of carrying out the provisions of this contract and shall not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract. The Contractor assumes responsibility for protection of the confidentiality of Government records and shall ensure that all work performed by its employees and subcontractors shall be under the supervision of the Contractor. Each Contractor employee or any of its subcontractors to whom any FDA records may be made available or disclosed shall be notified in writing by the Contractor that information disclosed to such employee or subcontractor can be used only for that purpose and to the extent authorized herein.

The confidentiality, integrity, and availability of such information shall be protected in accordance with HHS and FDA policies. Unauthorized disclosure of information will be subject to the HHS/FDA sanction policies and/or governed by the following laws and regulations:

18 U.S.C. 641 (Criminal Code: Public Money, Property or Records);

18 U.S.C. 1905 (Criminal Code: Disclosure of Confidential Information); and 44 U.S.C. Chapter 35, Subchapter I (Paperwork Reduction Act).

6) Internet Protocol Version 6 (IPv6). All procurements using Internet Protocol shall comply with OMB Memorandum M-05-22, Transition Planning for Internet Protocol Version 6 (IPv6).

7) Government Websites. All new and existing public-facing Government websites must be securely configured with Hypertext Transfer Protocol Secure (HTTPS) using the most recent version of Transport Layer Security (TLS). In addition, HTTPS shall enable HTTP Strict Transport Security (HSTS) to instruct compliant browsers to assume HTTPS at all times to reduce the number of insecure redirects and protect against attacks that attempt to downgrade connections to plain HTTP. For internal-facing websites, the HTTPS is not required, but it is highly recommended.

8) Contract Documentation. The Contractor shall use FDA-provided templates, policies, forms and other agency documents to comply with contract deliverables as appropriate.

9) Standard for Encryption. The Contractor (and/or any subcontractor) shall:

Comply with the HHS Standard for Encryption of Computing Devices and Information to prevent unauthorized access to government information.

Encrypt all sensitive federal data and information (i.e., PII, protected health information [PHI], proprietary information, etc.) in transit (i.e., email, network connections, etc.) and at rest (i.e., servers, storage devices, mobile devices, backup media, etc.) with FIPS 140-2 validated encryption solution.

All devices (i.e.: desktops, laptops, mobile devices, etc.) that store, transmit, or process non-public FDA information should utilize FDA-provided or FDA information security authorized devices that meet HHS and FDA-specific encryption standard requirements. Maintain a complete and current inventory of all laptop computers, desktop computers, and other mobile devices and portable media that store or process sensitive government information (including PII).

10) Contractor Non-Disclosure Agreement (NDA). Each Contractor (and/or any subcontractor) employee having access to non-public Government information under this contract shall complete the FDA non-disclosure agreement (3398 Form), as applicable. A copy of each signed and witnessed NDA shall be submitted to the CO and/or COR prior to performing any work under this acquisition.

11) Privacy Threshold Analysis (PTA)/Privacy Impact Assessment (PIA) – The Contractor shall assist the procuring activity representative, program office and the FDA SOP or designee with conducting a PTA for the information system and/or information handled under this contract to determine whether or not a full PIA needs to be completed.

B. Training

1) Mandatory Training for All Contractor Staff. All Contractor (and/or any subcontractor) employees assigned to work on this contract shall complete the applicable FDA Contractor Information Security Awareness, Privacy, and Records Management training (provided upon contract award) before performing any work under this contract. Thereafter, the employees shall complete FDA Information Security Awareness, Privacy, and Records Management training at least annually, during the life of this contract. All provided training shall be compliant with HHS and FDA training policies.

2) Role-based Training. All Contractor (and/or any subcontractor) employees with significant security responsibilities (as determined by the program manager) must complete role-based training annually commensurate with their role and responsibilities in accordance with HHS and FDA policy and FDA Role-Based Training (RBT) of Personnel with Significant Security Responsibilities Standard Operating Procedures (SOP).

3) Training Records. The Contractor (and/or any subcontractor) shall maintain training records for all its employees working under this contract in accordance with HHS and FDA policy. A copy of the training records shall be provided to the CO and/or COR within 30 days after contract award and annually thereafter or upon request.

C. Rules of Behavior The Contractor (and/or any subcontractor) shall ensure that all employees performing on the contract comply with the HHS Information Technology General Rules of Behavior.

All Contractor employees performing on the contract must read and adhere to the Rules of Behavior (ROB) before accessing HHS and FDA data or other information, systems, and/or networks that store/process government information, initially at the beginning of the contract and at least annually thereafter, which may be done as part of annual FDA Information Security Awareness Training. If the training is provided by the Contractor, the signed ROB must be provided as a separate deliverable to the CO and/or COR per defined timelines.

C. Incident Response The Contractor (and/or any subcontractor) shall respond to all alerts/Indicators of Compromise (IOCs) provided by HHS Computer Security Incident Response Center (CSIRC)/FDA SMC /Incident Response Team (IRT) teams within 24 hours, whether the response is positive or negative.

FISMA defines an incident as “an occurrence that (1) actually or imminently jeopardizes, without lawful authority, the integrity, confidentiality, or availability of information or an information system; or (2) constitutes a violation or imminent threat of violation of law, security policies, security procedures, or acceptable use policies.” The HHS Policy for IT Security and Privacy Incident Reporting and Response further defines incidents as events involving cybersecurity and privacy threats, such as viruses, malicious user activity, loss of, unauthorized disclosure or destruction of data, and so on.

A privacy breach is a type of incident and is defined by FISMA as the loss of control, compromise, unauthorized disclosure, unauthorized acquisition, or any similar occurrence where (1) a person other than an authorized user accesses or potentially accesses personally identifiable information or (2) an authorized user accesses or potentially accesses personally identifiable information for another than authorized purpose. The HHS Policy for IT Security and Privacy Incident Reporting and Response further defines a breach as “a suspected or confirmed incident involving PII.”

In the event of a suspected or confirmed incident or breach, the Contractor (and/or any subcontractor) shall:

cooperate and exchange any information, as determined by the Agency, necessary to effectively manage or mitigate a suspected or confirmed breach;

not include any sensitive information in the subject or body of any reporting e-mail; and encrypt sensitive information in attachments to email, media, etc.

E. Position Sensitivity Designations All Contractor (and/or any subcontractor) employees must obtain a background investigation commensurate with their position sensitivity designation that complies with Parts 1400 and 731 of Title 5, Code of Federal Regulations (CFR). The following position sensitivity designation levels apply to this solicitation OR contract: [See the FDA Security Article, entitled Contractor Personnel Security Clearance Standards and Residency Requirements for the Position Risk Designation Tier(s) (i.e., 1, 2, and/or 4) that apply to this award.] F. Homeland Security Presidential Directive (HSPD)-12 The Contractor (and/or any subcontractor) and its employees shall comply with Homeland Security Presidential Directive (HSPD)-12, Policy for a Common Identification Standard for Federal Employees and Contractors; OMB M-05-24; FIPS 201, Personal Identity Verification (PIV) of Federal Employees and Contractors; HHS HSPD-12 policy; and Executive Order 13467, Part 1 §1.2.

Roster. The Contractor (and/or any subcontractor) shall submit a roster by name, position, e-mail address, phone number and responsibility, of all staff working under this acquisition where the Contractor will develop, have the ability to access, or host and/or maintain a government information system(s). The roster and any revisions to the roster as a result of staffing changes shall be submitted to the COR and/or CO per the COR or CO’s direction. Any revisions to the roster as a result of staffing changes shall be submitted within a timeline as directed by the COR and/or CO. The COR will notify the Contractor of the appropriate level of investigation required for each staff member.

If the employee is filling a new position, the Contractor shall provide a position description and the Government will determine the appropriate suitability level.

G. Contract Initiation and Expiration General Security Requirements. The Contractor (and/or any subcontractor) shall comply with information security and privacy requirements, Enterprise Performance Life Cycle (EPLC) processes, HHS Enterprise Architecture requirements to ensure information is appropriately protected from initiation to expiration of the contract. All information systems development or enhancement tasks supported by the Contractor shall follow the FDA EPLC framework and methodology in accordance with the FDA EPLC Project documentation, located at: here: http://sharepoint.fda.gov/orgs/DelMgmtSupport/IntakeProc/EPLCv2/SitePages/v2/EPLCHome.aspx HHS EA requirements may be located here: https://www.hhs.gov/about/agencies/asa/ocio/index.html.

System Documentation. Contractors (and/or any subcontractors) must follow and adhere to NIST SP 800-64, Security Considerations in the System Development Life Cycle, at a minimum, for system development and provide system documentation at designated intervals (specifically, at the expiration of the contract) within the EPLC that require artifact review and approval.

Sanitization of Government Files and Information. As part of contract closeout and at expiration of the contract, the Contractor (and/or any subcontractor) shall provide all required documentation in accordance with FDA OAGS SMGs to the CO and/or COR to certify that, at the government’s direction, all electronic and paper records are appropriately disposed of and all devices and media are sanitized in accordance with NIST SP 800-88, Guidelines for Media Sanitization and FDA IS2P Appendix T: Sanitization of Computer-Related Storage Media Notification. The Contractor (and/or any subcontractor) shall notify the CO and/or COR as soon as it is known that an employee will stop working under this contract.

Contractor Responsibilities Upon Physical Completion of the Contract. The Contractor (and/or any subcontractors) shall return all government information and IT resources (i.e., government information in non-government-owned systems, media, and backup systems) acquired during the term of this contract to the CO and/or COR. Additionally, the Contractor shall provide a certification that all government information has been properly sanitized and purged from Contractor-owned systems, including backup systems and media used during contract performance, in accordance with HHS and/or FDA policies.

The Contractor (and/or any subcontractor) shall coordinate with the COR via email, copying the Contract Specialist, to ensure that the appropriate person performs and documents the actions identified in the FDA eDepart system http://inside.fda.gov:9003/EmployeeResources/NewEmployee/eDepartDepartureSystem/default.htm as soon as it is known that an employee will terminate work under this contract within days of the employee’s exit from the contract. All documentation shall be made available to the CO and/or COR upon request.

H. Records Management and Retention The Contractor (and/or any subcontractor) shall maintain all information in accordance with Executive Order 13556 - Controlled Unclassified Information, National Archives and Records Administration (NARA) records retention policies and schedules and HHS/FDA policies and shall not dispose of any records unless authorized by HHS/FDA.

In the event that a Contractor (and/or any subcontractor) accidentally disposes of or destroys a record without proper authorization, it shall be documented and reported as an incident in accordance with HHS/FDA policies.

The Contractor shall have a documented record of conducting implant studies/evaluations, and the employees assigned to this project shall have prior large-animal surgical experience. Proposals shall include comprehensive study plans, with relevant in-life study periods, that simulate chronic exposure to a metal-containing device and outline histopathological and immunological assessments. They should not include clinical-assessment studies.

Contracting Officer’s Technical Point of Contact (TPOC)

The TPOC is responsible for the acceptance of the items or services requested.

Technical Direction

Technical direction shall be within the general scope of work stated in the contract. The TPOC does not have the authority to, and may not, issue any technical direction which (1) constitutes an assignment of additional work outside the general scope of the contract; (2) constitutes a change as defined in the contract clause entitled "Changes, FAR 52.212 – 4 (c)."

(3) in any manner causes an increase or decrease in the total contract price; or (4) changes any of the expressed terms, conditions, or specifications of the contract.

All technical directions shall be issued in writing by the TPOC or shall be confirmed by him/her in writing within five (5) working days.

The Contractor shall proceed promptly with the performance of technical directions duly issued by the TPOC in the manner prescribed by this clause and within his/her authority under the provisions of this clause.

If, in the opinion of the Contractor, any instruction or direction issued by the TPOC is within one of the categories as defined in B. (1) through B. (4) above, the Contractor shall not proceed but shall notify the Contracting Officer, in writing, within five (5) working days after the receipt of any such instruction or direction and shall request the Contracting Officer to modify the Contract accordingly. Upon receiving such notification from the Contractor, the Contracting Officer shall issue an appropriate contract modification or advise the Contractor, in writing, that, in his/her opinion, the technical directions are within the scope of this clause and do not constitute a change under the "Changes" clause of the contract. The Contractor shall thereupon proceed immediately with the direction given. Any failure of the parties to agree upon the nature of the instruction or direction, or upon the contract action to be taken with respect thereto, shall be subject to the provisions of the contract clause entitled "Disputes."

Contracting Officer’s Authority

The Contracting Officer (CO) is the only person authorized to approve changes in any of the requirements of the statement of work. In the event the Contractor effects any changes at the direction of any person other than the CO or the TPOC the changes shall be considered to have been made without authority and no adjustment shall be made in the contract price to cover any increase in costs incurred as a result thereof. The CO shall be the only individual authorized to accept nonconforming work, waive any requirement of the contract and modify any term or condition of the contract. The Contracting Officer is the only individual who can legally obligate Government funds.

The Contracting Officer is the only person with authority to act as agent of the Government under the Contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor for any costs incurred during the performance of the Contract; or (5) otherwise change any terms and conditions of the Contract.

Section 4 - Contract Clauses FAR 52.212-4 - Contract Terms and Conditions – Commercial – Items (Oct 2018).

FAR 52.252-2 - Clauses Incorporated by Reference (Feb 1998)

This contract incorporates one or more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at these addresses: www.acquisition.gov/far/index.html and http://www.hhs.gov/policies/hhsar/subpart301- 1.html.

FAR Clause Title Date Reference 52.203-3 Gratuities Apr 1984 3.202 52.203-17 Contractor Employee Whistleblower Rights and Requirement to Inform Employees of Whistleblower Rights.

Jun 2020 3.908-9 52.204-7 System for Award Management.

Oct 2018 4.1105(a)(1) 52.204-14 Service Contract Reporting Oct 2016 4.1705(a) 52.245-1 Government Property Jan 2017 52.245-1

HHSAR

Title Date Date 352.211-3 Paperwork Reduction Act.

Dec, 2015 311.7301 352.222-70 Contractor Cooperation in Equal Employment Opportunity Investigations Dec, 2015 322.810(h) 352.227-14 Rights in Data—Exceptional Circumstances.

Sept 2014 327.409 352.239-74 Electronic Information and Technology Accessibility Notice.

Dec 2015 339.203-70(b) Health and Human Services Acquisition Regulation (HHSAR) Clauses can be viewed in full text at: http://www.hhs.gov/policies/hhsar/subpart352.html#Subpart352.1- InstructionsforUsingProvisionsandClauses

FAR 52.217-8 - Option to Extend Services. (Nov 1999)

The Government may require continued performance of any services within the limits and at the rates specified in the contract. These rates may be adjusted only as a result of revisions to prevailing labor rates provided by the Secretary of Labor. The option provision may be exercised more than once, but the total extension of performance hereunder shall not exceed 6 months. The Contracting Officer may exercise the option by written notice to the Contractor any time before the contract expires.

Federal and HHS Information Security Program Policies

This contract requires the Contractor, pursuant to Federal and HHS Information Security Program Policies, and any subcontractor performing under this contract, to comply with the following requirements:

Contractor-Employee Non-Disclosure Agreements: Each Contractor/subcontractor employee who may have access to non-public Department information under this contract shall complete the Commitment to Protect Non-Public Information – Contractor Agreement (http://nitaac.nih.gov/downloads/ciosp2/Contractor Employee Non-Disclosure.doc).

A copy of each signed and witnessed Non-Disclosure agreement shall be submitted to the COR prior to performing any work under the contract.

Confidential Treatment of Sensitive Information: The Contractor shall guarantee strict confidentiality of the information/data that it is provided by the Government during the performance of any task order issued under this contract.