The Department of Health and Human Services, Food and Drug Administration has a requirement for Post-Market Bioequivalence Studies

FDA has identified topics for which post-market Bioequivalence (BE) studies would be necessary to address scientific questions or quality concerns of specific generic drug products. For instance, FDA is interested in whether formulation complexity or post-marketing reports of therapeutic inequivalence warrant additional BE evaluation of generic modified release drug products. In vivo BE studies with fully replicated design may be desirable to evaluate the effect of formulation differences on the pharmacokinetic (PK) behavior of these products. Multiple studies may be necessary to cover a range of products including those containing controlled drug substances. Studies may not be limited to pos-market BE evaluation and may include pharmacodynamic endpoint assessments. To this end, this contract is to conduct BE studies of generic drug products to proactively address controversial scientific questions in developing generic approval standards and to help address public concerns regarding the quality of specific generic drug products.

• The objective of this project is to conduct appropriate Human Subject Research (HSR) studies of generic drug products in healthy subjects or patients as determined by the question of interest. The outcome of this project will help address scientific questions in developing generic approval standards and help address public concerns regarding the quality of specific generic drug. Additionally, this project will help improve the review practice of generic drug products and develop -associated guidance when applicable.

The contractor shall:

1. In discussion with FDA, perform quality characterization on drug productsincluding but not limited to dissolution and assay of drug substance and related substances in accordance with the United States Pharmacopeia standards if needed
2. Design the study and develop protocol in discussion with FDA for the planned studies. It may not be limited to BE/PK studies. The Contractor shall perform statistical analysis to modify the number of subjects in order to achieve sufficient study power if appropriate
3. Submit protocol, informed consent form and any related documents needed for in vivo BE/PK studies to a local Institutional/Independent Review Board (IRB) for review and obtain approval before conducting any clinical studies
4. Draft, revise and finalize all study documents and/or template including protocol, informed consent, plans, reports, essential documents, and source documents in English. Report and complete all study documents effectively in English
5. Develop an appropriate bioanalytical method, submit a validation report, and perform sample analysis including Incurred Sample Reanalysis. Depending on a study, multiple analytes including, but not limited to a metabolite may be needed. FDA’s 11 guidance on “Bioanalytical Method Validation: Guidance for Industry” (May 2018) should be followed for reporting on bioanalytical method parameters
6.  Procure study drugs as needed. Most BE/PK studies require the procurement of multiple bottles of the same lot
7. Conduct clinical studies and monitor and record adverse events through the study in accordance with all applicable regulations/guidance/policies including, but not limited to 45 CFR 46, 21 CFR, and Good Clinical Practice
8. Consult OGD Project Officer (PO) for any proposed changes to the study documents or the procedures prior to implement any changes
9. Establish and maintain all essential documents. It may include a regulatory submission including, but not limited to Investigational New Drug and Investigational Device Exemption. Ensure all records that are generated during the project are maintained and retained in accordance with all applicable regulations, policies, and guidelines
10. In discussion with FDA, act as an IND and/or IDE holder and assume responsibilities as needed
11. Generate preliminary data in a timely manner and subsequently submit clinical study report on the BE/PK evaluation of study product and on safety outcome of the BE/PK study
12. Be responsible for subject recruitment, supplies, equipment, and computational software. May need to recruit a patient population
13. Recruit diverse racial and/or ethnic populations representative of the general population in the United States as needed. A large database including active participants with various demographics is preferred
14. Deliver the required data as outlined in each task order. The primary, secondary and exploratory (if applicable) endpoint data shall be available for completed subjects
15. In discussion with FDA, work to resolve any foreseeable and/or unforeseeable issues. This may include a delay in planning and/or an implementation of preventive measures
16. Acquire clinical trial liability insurance against all liabilities, damages, losses, injuries, complaints and/or claims arising from the trial including, but not limited to, claims that arise from malpractice and/or negligence. Account for the costs of this insurance in the budget and will be responsible for maintaining an insurance certificate that satisfies any relevant regulations/guidance/policies including local requirements
17. Provide the project management oversight for each task order
18. Be responsible for replacement or corrections to the deliverables to meet the requirements identified in the task order
19. Work with the OGD COR, PO and/or Quality Assurance (QA) team, accommodate visit requests, and always make all study documents available for monitoring/inspection
20. Manage subcontractor(s) and assume all responsibilities if subcontract(s) becomes necessary
21. Remote site access, direct data entry/capture and/or remote monitoring platform/capability are preferred
22. Assume the responsibility and manage all Clinical Data Management (CDM) activities