FDA's Computer Validation Concerns: A Call for Improved Inspector Training and Quality Systems Approach

Strategic Insights -

Regulatory inspections at the FDA have raised concerns about computer validation, with the agency's Small Business Representative, Marie Falcone, pointing to a low rate of citations for this issue in fiscal 1998. Despite the FDA's educational efforts and industry's good job, Falcone believes that deficiencies in the agency's inspection procedures and training of inspectors are more likely to blame. Manufacturers may face future problems due to unaddressed computer validation issues, highlighting the need for a quality systems approach to ensure accurate inspections and improved productivity.

Key Takeaways:

  • In fiscal 1998, computer validation ranked 18th among reasons for withhold recommendations on NDAs and ANDAs, equaling six other categories, with 6 drug applications withheld due to computer and software validation issues.
  • FDA had anticipated getting more 483 citations and is now "looking into" why computer validation was not cited more often, with Falcone attributing this to deficiencies in the agency's inspection procedures.
  • Manufacturers may have computer validation problems that may be problematic in future inspections even if they were not previously cited, suggesting the need for improved training of inspectors on computer validation.
  • A quality systems approach, such as the one utilized by Alcon Labs, can help manufacturers pass FDA inspections and improve their bottom line, with a return on investment of 500% due to a 35% increase in productivity and a 39% decrease in defects.
  • The FDA's device Quality System regulation (21 CFR 820) and the Center for Devices draft guidance "General Principles of Software Validation" can provide guidance for manufacturers in implementing a quality systems approach to computer validation.
  • The GMP/Design Controls Handbook ($149) and the draft software validation guidance ($12, Doc. 111603) are available resources for manufacturers.

Statistics:

  • 18th among reasons for withhold recommendations on NDAs and ANDAs in fiscal 1998, with six other categories equal in ranking.
  • 6 drug applications withheld due to computer and software validation issues in fiscal 1998.
  • 500% return on investment due to a 35% increase in productivity and a 39% decrease in defects as reported by the Software Engineering Institute at Carnegie-Mellon University (Publication CMU/ SEI-94-TR-013).
  • 35% increase in productivity due to a quality systems approach, as reported by the Software Engineering Institute.

Sources:

  • Marie Falcone, Small Business Representative for the Mid-Atlantic Region, FDA
  • Dr. Richard Chamberlain, Ph.D., President of Executive Consultant Services
  • Carla Welch, BASF
  • Grant Hodgkins, Manager of Corporate Validation-Information Systems for Alcon Labs
  • Software Engineering Institute at Carnegie-Mellon University (Publication CMU/ SEI-94-TR-013)
  • FDA's device Quality System regulation (21 CFR 820)
  • Center for Devices draft guidance "General Principles of Software Validation" (Doc. 111603)