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Pharmaceutical industry

FDA Scrutinizes Development Reports in Post-Approval GMP Inspections

Strategic Insights

— 2 min read

FDA officials and compliance consultants pointed out during the International Business Communications' (IBC) FDA Compliance Summit in Coronoado, CA, that development reports are being closely examined in post-approval Good Manufacturing Practice (GMP) inspections for both drugs and biologics. This trend was echoed by biotech executives, who reported that inspectors are scrutinizing these documents so much that some companies are drafting Standard Operating Procedures (SOPs) to write development reports on new drugs. The importance of development reports in ensuring a company's compliance with GMP regulations was emphasized by Dr. Laureen Little, a biotech industry consultant, who recalled a field investigator examining retention samples to determine that a company had changed some practices during lyophilization without updating their development reports.

Key Takeaways:

  • Development reports are a crucial component of GMP inspections, and companies are being forced to revisit their procedures to ensure compliance.
  • The reports should include data regarding the manufacturing process, formulations, equipment for scale-up, manufacturing procedures, and testing/acceptance criteria for in-process and finished product samples.
  • The FDA emphasizes that while a formal development document is not required, the reports should establish batch size requirements, assure equivalence of pilot scale or scale-up batches with commercial-sized batches, and evaluate failures.
  • Companies are finding it difficult to get their product development teams to write development reports, highlighting the need for better communication and integration between QA, RA, and product development teams.
  • The use of the ISO/Quality Systems (QS) approach to QA has helped companies like Protein Design Labs pass EU inspections, but the development report facet of the manual can be challenging to implement.
  • The FDA has been ramping up audits of APIs, with more than 80% of finished drugs sourced from overseas bulk, and the agency's inability to meet its ambitious 1995 goal of performing 60% of inspections in foreign lands.
  • The top GMP deficiencies cited in FDA statistics for 1999 include laboratory controls, equipment cleaning, records and reports, in-process controls, and component controls.

Statistics:

  • 16% of finished dosage manufacturers failed Process for NDA holders.
  • 81% of ANDA rejections were due to firms not being ready.
  • The most common current GMP deficiencies encountered in 1999 were laboratory controls (16%), equipment cleaning (13%), records and reports (13%), in-process controls (10%), and component controls (8%).
  • In fiscal 2000, only 6% of all FDA audits were conducted overseas.
  • The FDA is piloting "systems-based inspections," examining four key areas of company quality systems.

Sources:

  • IBC's FDA Compliance Summit, Coronoado, CA, Dec. 13
  • AAPS' pre-approval inspection conference in Arlington
  • Joseph Phillips, deputy director of FDA's Central Region in Philadelphia, at AAPS' meeting on Jan. 8
  • Nicholas Buhay, of the Center for Drugs Division of Manufacturing and Product Quality, at AAPS' meeting
  • Dr. Paul Wray, Ph.D., of International Pharmaceutical Services, at AAPS' meeting
  • FDA's data for 1999 on GMP deficiencies and API inspections
  • ISO/Quality Systems (QS) approach to QA

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