FDA Enforcement Trends: 2007-2008

Guest content from John Avellanet, managing director of Cerulean Associates:

The US Food and Drug Administration (FDA) intends to increase regulatory enforcement, extending the recent trend of laboratory and clinical site inspections to unapproved drugs and reformulations. How can you avoid compliance trouble?

At the Food and Drug Law Institute’s 5th Annual Enforcement and Litigation conference, several FDA compliance directors spoke out on FDA enforcement priorities and provided recommendations to improve compliance.

Laboratory & Clinical Inspections
The first two targets for enforcement are laboratories and clinical sites. Of the violations found, data integrity and policy/protocol adherence are the top two by a large margin, with data integrity involved in 95% of findings. Mitch Lazris, an industry defense attorney, noted that IT departments continue to be the weak link in the compliance chain.

Two main factors lead to inspections: problems with the integrity of the information submitted to the FDA and complaints by former employees, contractors, vendors, clinical trial participants and even the sponsors themselves.

Unapproved Drugs
The FDA estimates that approximately 2% of all prescriptions are for unapproved drugs or formulations. Priority will be given to those drugs that pose safety risks, with pediatric formulations at the top of the list. Drugs that lack evidence of efficacy are also considered to be “unapproved” now that all “generally recognized as safe” (GRAS) interpretations were revoked in 1968 (21 CFR 310.100).

Recommendations
Panel members made multiple concrete suggestions for executives:

1. Conduct benefit-risk analyses for every product-related decision (such as labeling, reformulation, etc.); ask yourself how you’ll defend the decision in front of jurors increasingly suspicious of the high profits of (big) “pharma.”
2. Train individuals to understand what they are committing to, not just the procedure or protocol steps.
3. Clarify to IT their accountabilities for electronic data integrity—there are no magic bullet technological solutions, so be wary of “another system” to solve the problem; push for a “quality” approach, not a technological one.
4. Use caution with universities that perform both the role of sponsor and investigator for clinical trials. Segregation of duties is critical.
5. Do not use reputation or brand to select sites, vendors or systems; inspectors look for information integrity and process adherence.
6. Rapidly respond to 483s as this shows you understand the gravity of the findings and have a positive attitude about the need for compliance.
7. Use design control to your advantage to minimize risks during clinical trials, labeling decisions and so forth.
8. Address all findings from audits, 483s and so on; remember to document the steps taken and the results. Expect the FDA to pursue court action if you insist on only fixing one or two items.

Following the panel’s recommendations will give you a stronger compliance program, minimize your costs, improve your bottom line and help you avoid enforcement action.
More recommendations and compliance strategies are on the Cerulean website.

About the Author
John Avellanet is a leading authority on simplifying and streamlining regulatory compliance and quality system programs so clients can achieve faster time-to-market. He can be reached through his independent consultancy, Cerulean Associates LLC (www.ceruleanllc.com) at: john[at]ceruleanllc.com.