FDA Regulation Regarding Acceptance for Foreign Data for US Marketing Approval

A pharmaceutical sponsor who relies on foreign data from a clinical study to support an Investigational New Drug (IND) application and clinical submission for US marketing approval must adhere to requirements cited in 21 CFR 312(b). The pharmaceutical sponsor must submit the following information to FDA:

• Description of clinical investigator's qualifications
• Description of clinical research facilities
• Description of clinical trial site
• Detailed summary of the clinical study protocol
• Finished, complete, ICH compliant final clinical study report (CSR)
• Patient Case Report Forms (CRFs) maintained by the clinical investigator at the clinical trial site - FDA will request CRFs, often there is a question as to whether a request by FDA will be made - prepare ahead of time - the compilation, collation, collection and submission of CRFs is time and labor intensive - the submitted file must be properly formatted, quality-controlled and quality-assured by qualified documentation experts
• Description of drug product and drug substance including components, formulation, specifications and bioavailability, CMC for starters
• If the clinical study is intended to support effectiveness and safety, the data and documentation must be collected, maintained and managed in accordance with 21 CFR 314.26 GCP.

Regarding Good Clinical Practice and foreign data, GCP must be followed to protect clinical study participants and ensure data and documentation integrity and quality. Final clinical study reports must be prepared in accordance with ICH GCP, including review and approval by an Independent Ethics Committee (IEC). FDA directs the review, inspection efforts and acceptance of foreign clinical study data for marketing approval under the Proposed Rule for Human Subject Protection published June 2004. The rule may be viewed at www.fda.gov/OHRMS/DOCKETS.

Under special consideration, FDA may consider foreign clinical study data to support a marketing approval on its own merit. The criteria for such a marketing application and clinical submission are cited in 21 CFR 314.106(b). Under 21 CFR 314.106(b), foreign clinical study data used to support a marketing application and clinical submission on its own merit must comply with the following requirements:

• Data and documentation are applicable and consistent with US medical practice and population demographics and statistical considerations
• Clinical investigators are qualified
• Data and documentation are of high quality
• Data and documentation are valid without FDA inspection
• Data and documentation are ICH compliant
• Data and documentation are collected under GCP
• Data and documentation are complete, quality-controlled and quality-assured
• Data and documentation are quality managed
• Data and documentation are collected by qualified clinical research associates (CRAs)
• Data and documentation are adequately monitored in accordance with GCP
• FDA may and will inspect the clinical trial site (facility) to ensure validity of data and documentation.