ATTACHMENT_3_Statement_of_Work_CPQA_15_Amendment__1_FINAL.pdf

ATTACHMENT 3: STATEMENT OF WORK

CLINICAL PHARMACOLOGY QUALITY ASSURANCE (CPQA)

RFP NO. NIAID-DAIDS-NIHAI2014002

1) BACKGROUND AND INTRODUCTION

The mission of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) is to help ensure an end to the HIV/AIDS epidemic by increasing basic knowledge of the pathogenesis and transmission of HIV disease, supporting the discovery and development of therapies for HIV infection and its complications, and supporting the discovery and development of vaccines and other prevention strategies.

The purpose of the NIAID Clinical Pharmacology Quality Assurance (CPQA) program is to provide a comprehensive quality assessment program for clinical pharmacologic laboratories testing samples from subjects enrolled in NIAID-supported clinical studies. The CPQA program ensures the validity and inter-and intra-laboratory comparability of pharmacological study data by providing laboratories with materials for pharmacology proficiency testing and assay controls, and monitoring proficiency and assay data from each laboratory. The program also implements standards of performance for new pharmacology assays, develops and tests methods relating to the assays, and acquires, tests, stores and dispenses quality control materials and reagents. Thus, the CPQA program is critical to the scientific integrity of on-going and future studies concerning assessment of anti-HIV treatments and preventive measures.

The CPQA was established in 2008 under a contract with the Research Foundation of State University of New York, Contract No, HHSN272200800019C. The current contract provides services to 11 U.S. and non-U.S. clinical pharmacology laboratories (Labs) affiliated with NIAID-supported clinical trial networks and collaborating study groups (User Groups).

Current User Groups include: the Adult AIDS Clinical Trials Group (ACTG), the International Maternal Pediatric and Adolescent AIDS Clinical Trials Group (IMPAACT), the HIV Prevention Trials Network (HPTN), the HIV Vaccine Trials Network (HVTN), the HIV Microbicide Trials Network (MTN), the Women's Interagency HIV Study (WIHS), the Multicenter AIDS Cohort Study (MACS), as well as other U.S. and non-U.S. clinical laboratories performing pharmacology testing for NIAID-supported clinical trials. Labs are chosen by User Groups to participate in a clinical trial. It is critical to evaluate, both initially and on an on-going basis, the ability of Labs to perform protocol-specified pharmacology assays correctly and reliably.

2) SCOPE

The Contractor shall provide comprehensive quality assessment programs to clinical pharmacology laboratories (Labs) that test samples from subjects

Attachment 3: Statement of Work (September 25, 2013) Page 1 enrolled in NIAID-supported clinical studies. The Contractor shall (1) evaluate the ability of Labs to accurately and reliably perform study-specified pharmacology assays; (2) provide for the planning and execution of single and multi-Lab studies for the development, validation and implementation of bioanalytical methods for measuring drug concentrations in study specimens;

(3) acquire, characterize, store, and distribute to Labs quality control materials and reagents; (4) provide guidance and assistance to Lab and clinical site staff in proficiency testing, assay validation and in the conduct of clinical pharmacology studies; and (5) prepare Labs for FDA inspections and study audits. Options to provide increased effort for support for additional labs are also within the scope of the contract work.

3) TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment and facilities not otherwise provided by the Government as needed to perform the statement of work set forth below. The Contractor shall:

A. PROVIDE PHARMACOLOGY PROFICIENCY TESTING (PT)

1. Quality Assurance (QA) Standards for Executing Proficiency Testing

Develop and maintain Standard Operating Procedures (SOPs) and manuals for executing the Pharmacology PT Program, in compliance with CLIA regulations and other applicable federal, state, and local regulations.

2. Proficiency Testing (PT) Samples

As directed by the COR, provide panels of coded PT samples (unknown to Labs) corresponding to the assays conducted.

Note: User Groups determine which Labs will provide testing and which pharmacology assays are required for each clinical trial conducted.

a) Prepare PT panel samples that include the following:

1) drug analytes (e.g., nucleoside reverse transcriptase inhibitors(NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), chemokine receptor type 5 (CCR5) antagonists, integrase inhibitors, anti-tubercular (TB), anti- hepatitis C virus (HCV) drugs, and biological drug products);

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2) varying concentrations of each drug in relevant biomatrices (e.g., plasma, lymphatic tissue, rectal tissue, PBMC, hair, RBC, vaginal fluids, spinal fluids, milk, saliva) that span the expected therapeutic range of the drug;

3) human biomatrices without drugs to support the specificity of the PT sample within each laboratory assay method.

b) Confirm quality (e.g. impurities) of all PT samples prior to distribution.

c) Provide PT samples to Labs under conditions that ensure sample integrity.

d) Instruct Labs to indicate to the CPQA: 1) date of sample receipt, 2) sample integrity, 3) selected drugs to be tested, 4) assays to be used, and 5) testing results.

e) Provide Labs with format and deadline for reporting results to the

CPQA.

f) Receive, verify and analyze Labs PT results.

g) Provide to each Lab with a Lab-specific initial PT report, followed by a performance report at least one month prior to shipment of the next round of PT samples.

h) Prepare and submit to the COR and User Groups after each round of PT a Cumulative Performance Report delineating performance status of all Labs over time.

i) Discuss PT results with Labs, review corrective action plans from the Labs and assist Labs with implementation of these plans. As needed, provide Labs with remediation samples for re-testing.

Analyze data from the remediation samples and report results to Labs, User Groups and COR.

B. SUPPORT ASSAY DEVELOPMENT, VALIDATION, AND

IMPLEMENTATION

1. Bioanalytical Assay Development

As needed, provide support to Labs conducting studies for the development, validation and implementation of pharmacology assays

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(e.g., assays for novel biomatrices, new drugs, and drug metabolites).

These studies, conducted by the Labs, must be in compliance with cGLP (21 CFR part 58), and applicable federal, state, and local regulations. Specifically:

a) Provide Labs with quality control (QC) materials similar to those described in section A.2 above for drug stability studies.

b) Develop procedures that refine and improve sampling process, sample processing and storage of non-plasma biological samples.

2. Bioanalytical Assays Validation

a) Assist Labs in determining the need for validation and partial validation experiments, including assays to be transferred to another Lab; Instruct Labs in the construction of Assay Validation Reports (AVR).

b) Review, evaluate and approve AVRs submitted by the Labs to ensure the accuracy, sensitivity, specificity, and precision or reproducibility of the methods. Notify the Labs whether AVRs are approved, approved with required minor revisions, or pending approval with further supporting data, within 10 business days of the completion of AVR review. Provide weekly an updated list of approved AVRs or AVRs under review to the COR.

c) Maintain and revise, as necessary, guidance documents for assay validation.

3. Assay Implementation

a) Develop and refine SOPs, QA documents, and guidance documents for assay implementation.

b) Develop policies needed by the Labs to improve the quality of pharmacology outcome measures.

c) Assist new Labs in initiating and implementing CPQA-approved methods.

d) Transfer validated assays to Labs upon the request of the COR.

The Contractor will be given three (3) months advance notice about the need to transfer such assays.

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C. ACQUIRE, CHARACTERIZE, STORE, DOCUMENT, AND DISTRIBUTE

QUALITY CONTROL MATERIALS (QCMS)

1. Acquisition of Analytical Grade Reference Standards

(AGRS)/Reference Drug Powder and Quality Control Reagents

a) Acquire, in compliance with FDA requirements, AGRS/reference drug powder from both commercial and non-commercial appropriate sources:

1) certified AGRS (e.g., USP reference standard),

2) reference drug powder source, and

3) reference drug powder.

b) Obtain AGRS/reference drug powder with relevant material safety data sheets (MSDS) and certificates of analysis (COAs).

c) Acquire unidentifiable human tissue samples (e.g., PBMC, hair) from commercial and non-commercial sources.

2. Characterization of AGRS/Reference Drug Powder and preparation of PT and QC Samples

Conduct initial and periodic purity checks on each lot of AGRS/reference drug powder.

3. Storage of AGRS/Reference Drug Powder, PT and QC Samples, and Reagents

Store characterized AGRS/reference drug powder, aliquots of PT and QC samples, and reagents under conditions that ensure continued activity and stability of materials.

4. Shipment of AGRS/Reference Drug Powder, PT and QC

Samples, and Reagents

As required, the Contractor shall ship AGRS/reference drug powder, PT and QC samples, and reagents to specified U.S. and non-U.S. Labs under appropriate shipping conditions (e.g., temperature monitoring) and in accordance with IATA/ICAO (http://www.iata.org/index.htm) and international Civil Aviation Organization(ICAO) (http://www.icao.int/) dangerous goods shipping regulations and other relevant shipping regulations. Additionally, the Contractor shall:

(September 25, 2013) Page 5 http://www.iata.org/index.htm http://www.icao.int/

a) Execute agreements with Labs regarding relevant standards for safe handling and authorized use and discard of AGRS/reference drug powder, PT and QC samples, and reagents.

b) Arrange overnight (or within 3 days if non-U.S. destination) delivery of shipments to the Labs.

c) Obtain the appropriate interstate and foreign shipping licenses and permits for transporting biohazard materials.

d) Coordinate the shipments of AGRS/reference drug powder, PT and QC samples, and reagents to the Labs, including notices of incoming shipments.

D. PROVIDE GUIDANCE AND ASSISTANCE

The Contractor shall use available methods such as telephone, email, and web conferencing to effectively communicate with the Labs to provide guidance and assistance to perform pharmacological assays reliably and validate assays correctly and to effectively communicate with clinical sites guidance for the appropriate acquisition and processing of subject samples for pharmacological testing. The Contractor shall:

1. Prepare and provide Labs with procedures/SOPs for performing pharmacological assays and for conducting assay validating studies.

2. Initiate an investigation of the root causes of performance failure and steps for corrective action.

3. Review corrective action plans from the Labs and assist with implementation of the plans.

4. As needed, after implementation of corrective measures, provide Labs with QCMs for retesting by the Labs, and report results to Labs, User Groups and COR.

5. Recommend to the COR the planning and conduct of visits to Labs to provide further guidance and assistance based on Lab-specific needs/performance. Submit to the COR a written plan providing relevant information including visit purpose/goals, duration, existing materials to be provided and/or new materials requiring preparation, names of visiting contract staff, and budget estimate. Within 10 business days of visit completion, prepare a report delineating observations, activities conducted, resolution of needs/problems and any recommended future plans for additional site-specific

(September 25, 2013) Page 6 guidance/assistance. Distribute the report to the visited Lab, User Groups and the COR.

6. At the request of the COR, make arrangements for visits to the

Contractor by Lab personnel for the purpose of providing guidance and assistance to the Lab personnel. The Contractor shall not be responsible for travel costs of participants.

7. Provide guidance, via an existing on-line tutorial, to clinical site staff

(e.g., nurses, study coordinators) on concepts of pharmacokinetics and pharmacodynamics, and guidance for the appropriate collection and processing of samples obtained from subjects participating in clinical trials.

8. Provide a certification to individuals that successfully complete the on-line tutorial.

9. Provide assistance and guidance to clinical investigators and technicians at NIAID-funded investigator meetings, in order to improve testing proficiency, optimize assay development, and achieve appropriate patient sample handling.

E. PREPARE LABS FOR FDA LABORATORY INSPECTIONS AND STUDY

AUDITS

As required and in preparation for FDA laboratory inspections and audits of clinical pharmacology studies, the Contractor shall visit Labs and determine the degree of compliance with CLIA, cGCP, cGLP, and other applicable federal, state, and local regulations. The level of cGCP shall be limited to specimen specific operations. The Contractor shall:

1. Assess overall quality of Lab operations, including organization, qualification and competency of Lab personnel; Lab quality management systems; instruments and test validation/performance verification; specimen management; laboratory data management;

equipment and equipment maintenance; and specific tests, including quality control and quality assurance.

2. Assess Lab compliance with clinical pharmacology study-specific requirements, including:

a) Examination of the inventory, traceability, and integrity of study samples (i.e., history and integrity; collection, receipt, storage, handling, stability).

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b) Examination of the quality of assay validation reports and associated SOPs.

c) Assessment of study-specific pharmacokinetic (PK) parameters and their relevance to the objectives of the study.

3. Assess event-driven causes for concern (e.g., determine if Lab results are traceable to quality operations).

4. Prepare and submit a final Lab Inspection Report to the Lab Principal Investigator/Site Director, the COR, and other relevant User Group(s) as specified by the COR.

5. Assist Labs in preparing remedial action plans to be completed by the

Lab prior to an audit by a regulatory entity.

6. Review Lab’s remedial action plans within 4 weeks after receipt from the Lab and indicate needed follow-up Contractor support.

F. HOST AND MAINTAIN COMPUTERIZED SOFTWARE SYSTEMS

The Contractor shall host and support an electronic data management system to track and make available documents in support of activities performed under the contract. The Contractor shall utilize the existing CPQA computerized data management system and update the system as necessary. The Contractor shall:

1. Host and Maintain software to store, organize, track, retrieve documents and reports on Lab-specific information and activities. The web-based application and other applicable internet and intranet information services provided at the web sites and web pages shall comply with Section 508, and meet the Section 508 accessibility standards.

2. Maintain and update Lab-specific documents/information such as Lab contact information, status of CLIA certification, proficiency testing performance records, assay development and validation reports, and reports of CPQA visits to Labs.

3. Provide software-specific security measures for Lab-specific proficiency testing data accessible only to Lab staff and to individuals identified by the COR.

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4. Maintain and update information related to AGRS, QC samples, and reagents, such as source, type, amounts, characteristics and lot numbers, shipping dates to Labs, stability data, and storage.

5. Track the certification status of clinical staff who have completed the on-line tutorial.

6. Maintain and update a public, searchable website with a document library for Labs and User Groups, which contains Contractor’s presentations, policies, news releases, and guidance materials/resources organized by categories. The searchable website shall comply with Section 508, and meet the Section 508 accessibility standards.

7. Provide tracking information for stored documents that includes name/type of document, description, author/origin, date received and date stored by the Contractor.

8. Maintain the computerized system security documentation as required by OMB Circular A-130, Appendix III and the Federal Information Security Management Act (FISMA). This shall include a comprehensive assessment of the management, operational, and technical security controls in the system to determine the extent to which the controls are implemented correctly, operating as intended, and producing the desired outcome with respect to meeting a specified set of security requirements for the system. These actions are referred to as System Assessment and Authorization (SA&A). The NIAID Information System Security Officer (ISSO) performs the Assessment to support the NIAID CIO decision to authorize operation of an information system and to explicitly accept the risk to NIAID data based on the implementation of an agreed-upon set of security controls. Authority To Operate is issued by NIAID.

G. ADMINISTRATIVE AND TECHNICAL SUPPORT

The Contractor shall be responsible for the following:

1. Meetings and Teleconferences

a) Annual Site Visits with the Contractor

Participate in an Annual Site Visit, with the first serving as a Contract Initiation Meeting at the Contractor’s site for the COR and government staff. The first meeting will be scheduled by the COR and take place within 30 days following the effective date of the

(September 25, 2013) Page 9 base contract. The meeting shall be attended by the Principal Investigator/Program Manager and other relevant key Contractor technical and business staff. The purpose of the first meeting shall be to inspect the Contractor’s facility, introduce Contractor and NIAID staff, review the terms and conditions of the contract, and discuss transition plans. All subsequent meetings will be held yearly, scheduled by the COR and the purpose will be to inspect the Contractor’s facility, discuss project progress and costs; problems, obstacles and approaches to overcoming them; recommendations for modifications in project timelines, objectives, and research approaches/methodologies based on outcomes to date; and future plans. If requested, provide meeting minutes to the COR within three business days of the conclusion of the meeting.

b) Plan and conduct periodic teleconferences with key Contractor staff, the COR, and other NIAID staff designated by the COR to review overall progress. Provide the COR with teleconference agendas and relevant materials.

c) As needed, plan and conduct teleconferences with key Contractor personnel and specific Lab investigators (identified by meeting content and agenda topic) to review Lab-specific problems, resolutions and progress towards achieving reliable performance.

H. EXECUTE INITIAL AND FINAL TRANISTION

1. Initial Transition

In the event of transition to a new contractor, the Contractor shall ensure an orderly, secure, and efficient transition of contract activities and contract-related data, documents, and other materials from the previous contractor, as follows:

a) Within 3 business days of the effective date of the contract, the

COR will provide the Contractor with a copy of the incumbent contractor’s Final Transition Plan specifying transition requirements and processes. The Initial Transition shall require the transfer of contract-related materials and data from the incumbent Contractor to the successor Contractor, which includes the following:

1) stored AGRS, PT samples, QC samples, and reagents;

2) all data files in computer readable format and software systems (with documentation and specifications) including systems for tracking PT and real-time assay validation data, AVRs, assay development research data, training records, records of Lab inspection and audits, inventory data, and

(September 25, 2013) Page 10 statistical analysis data (information shall be provided in electronic format and transferred in a secure manner as determined by the COR with input from the Contractor);

3) laboratory/manufacturer correspondence files, SOPs, and archived activity files for incoming and outgoing shipments;

and

4) Government Furnished Property (GFP), if applicable.

b) Within 10 business days of the effective date of the contract, the Contractor shall submit to the COR and Contracting Officer for approval, an Initial Transition Plan and timeline for the transition of activities and contract-related materials from the incumbent contractor, and the activities required for having the Contractor’s facility ready for providing support to Labs. The Plan shall include coordination with the Labs to ensure an orderly transition.

c) Upon COR and Contracting Officer approval of the Initial Transition

Plan, implement and complete the transition within 20 business days following the effective date of the contract.

2. Final Transition

a) Provide a Final Transition Plan for the orderly, secure and efficient transition of contract-related materials, data, and activities to a successor contractor or the Government, if a Contractor other than the incumbent is awarded a follow-up contract for this requirement.

This plan shall be subject to written approval by the COR and Contracting Officer.

b) The Draft Final Transition Plan shall be submitted to the COR and

Contracting Officer not later than 6 months prior to the completion date of the contract for review and comment. Upon receipt of comments, the Contractor shall revise the Draft Final Transition Plan as necessary.

c) The Final Transition Plan shall be submitted for written approval to the COR and Contracting Officer not later than 2 months prior to the completion date of the contract. The Contractor shall implement and complete the Transition Plan by the completion date of the contract. The Contractor shall maintain full operational capacity during the final transition period.

d) The transition process shall require the transfer of contract-related material to include:

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1) stored AGRS/drug powder, PT samples, QC samples, and reagents. The Contractor shall perform calibration and lot-to-lot comparisons between AGRS/drug powder, PT, QC samples, and reagents to be transferred to the successor Contractor;

2) all data files in computer readable format and software systems (with documentation and specifications) including systems for tracking PT and real-time assay validation data, AVRs, assay development research data, training records, records of Lab inspection and audits, inventory data, and statistical analysis data (information shall be provided in electronic format and transferred in a secure manner as determined by the COR with input from the Contractor);

3) laboratory/manufacturer correspondence files, SOPs, and archived activity files for incoming and outgoing shipments; and

4) Government Furnished Property (GFP), if applicable.

e) Notify all Labs as early as possible of the transition and provide schedules to the Labs for the transition, and instructions concerning any changes in testing schedules anticipated during the transition.

[END OF STATEMENT OF WORK FOR BASE PERIOD]

l. OPTIONS

In addition to the above functions and services to be provided for the Base period, the Government may exercise, at its discretion, Options for additional level of effort as follows: 1) Options to extend the term of the contract; and 2) Options to accommodate significant increases in work.

These Options are defined as follows:

1. Options 1 through 6 to extend the Term of the Contract: The

Government may exercise options to extend the period of the contract beyond the base period (Year 1), annually, for a total contract period of up to 7 years. Assume that the scope and types of activities as outlined herein (i.e., for Year 1 of the contract) would be continued for each succeeding annual contract period up to 7 total years.

2. Options 7 through 18 to Increase Services: The Government may exercise Options for an increased level of effort that may result from unanticipated increases in demand for the activities supported by the base requirements of this contract. Options for increased services may include the following:

a. Increased Level of Effort for Additional Labs (Options 7-18):

During the course of the contract, it may be necessary to

(September 25, 2013) Page 12 incorporate additional pharmacology laboratories. Such an increase would require an increase in the Contractor's activities to be activated, at the discretion of the Government, as an Option. Each Option of this type will implement work commensurate with the addition of one (1) domestic or international Lab. Up to two Options per year may be exercised during years 2 through 7 of contract performance. If the Government elects to exercise this Option, the Contractor shall provide an additional 0.9 FTE. The period of performance of an Option for Increased Services will not exceed the term of the base year or Option year in which the Option is exercised.

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