Brian Folian, Deputy Office Director, Office of Study Integrity and Surveillance (OSIS), CDER described the functions of his Office during the recent Association of Accessible Medicines GRx + Biosims conference. He noted that his Office is responsible for the oversight of study of the conduct of bioavailability, bioequivalence, pharmacokinetic, pharmacodynamic, good laboratory practice and animal rule studies supporting new and generic drug applications and biologics license applications. In addition, OSIS

  • Conducts and assigns inspections/remote regulatory assessments (RRA) to OII
  • Investigates allegations and complaints of regulatory non-compliance
  • Leads/supports CDER compliance-related actions
  • Collaborates with foreign regulatory authorities
  • Engages with industry

He noted that Remote Regulatory Assessments (RRAs), while relatively new and emerging from the COVID era, are neither inspections nor intended to serve as inspections. However, they represent a significant opportunity for modernization, particularly given FDA’s inspectional workload. Their reviews include analysis of analytical method validation, study sample analysis along with facility and equipment evaluation, workflow, staff training assessment and data security. From the data reviewer they can develop appropriate documentation and evaluate study re-construction.

He noted that “in the BA/BE space [OSIS has] seen concerning trend of unreliable/fraudulent data which undermines the safety, efficacy, and quality of medical product decisions”.

To help assure that the OSIS RRA is successful he provides the following recommendations:

  • Communication is an exchange like an inspection, so get clarity as necessary to ensure response address RRA requests and expect we will walk you through your site, records, etc.
  • Provide documentation to show that study records can be verified to allow study reconstruction? Provide complete, clear, and accurate records within the requested timeframe. Do not create records – if records do not exist, confirm that, delays in providing records should be rare if study records organized and controlled.
  • When explaining E-system data security, be clear on access privileges and data controls.
  • Respond to RRA Observations and implement CAPAs.

Mr. Folian also suggests that applicants select and verify the selected CROs to ensure they have the appropriate quality management system and that they demonstrate a good compliance history. He also reminds applicants that ultimately, the applicant is responsible for the quality and integrity of the study data contained in the application. Another point that may elude some applicants is that they should communicate with FDA early whenever concerns arise with full disclosure of the known and unknown.

This is good, sage advice from the Agency, especially given recent data integrity issues that have come to light in several well-publicized cases involving bioequivalence testing facilities. When you think about it, much of this advice also applies to drug manufacturers, CDMOs, and API manufacturers.