FDA Warning Letters in Early 2017 Highlight Need for GMP Audits at Foreign Sites

As of March 23, 2017, FDA’s Office of Manufacturing Quality in the Center for Drug Evaluation and Research (CDER) has released 17 Warning Letters, almost all of which targeting manufacturing sites abroad.

Although it’s too soon to tell if this trend reflects a shift toward increased foreign FDA inspections, it should be a stark warning to all pharmaceutical companies with manufacturing sites and/or contract manufacturers outside of the U.S. that foreign compliance should be a serious area of concern.

Of the Warning Letters issued so far this year, most of the issues cited in them occurred in 2016. More importantly, nearly all of them cite violations of current Good Manufacturing Practices and adulteration of drug products.

We’ve compiled links to each of these Warning Letters according to the general issue(s) cited, as well as important advice all manufacturers should take away from them.

FDA CDER Warning Letters So Far in 2017

1. (U.S.) Sponsor–Investigator
2. (China) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
3. (Japan) CGMP/Finished Pharmaceuticals/Adulterated
4. (China) CGMP/Finished Pharmaceuticals/Adulterated
5. (Italy) CGMP/Finished Pharmaceuticals/Adulterated
6. (India) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
7. (U.K.) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
8. (China) CGMP/Finished Pharmaceuticals/Adulterated
9. (China) CGMP/Finished Pharmaceuticals/Adulterated
10. (Japan) CGMP/Finished Pharmaceuticals/Adulterated
11. (India) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
12. (China) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
13. (India) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
14. (China) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated
15. (China) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated/Misbranded
16. (India) CGMP/Active Pharmaceutical Ingredient (API)/Adulterated/Misbranded
17. (India) CGMP/Finished Pharmaceuticals/Adulterated

    
    

Important Takeaways for Pharmaceutical Manufacturers 

• This enforcement trend proves just how important it is for companies to audit ALL facilities used for compliance with FDA requirements. All sites––whether an API or finished drug facility, domestic or foreign––must be audited by the manufacturer. [Free white paper: The Complete Guide to FDA-Regulated Supplier Qualification & Quality Management]
  
  
• GMP compliance issues at foreign firms can lead to greater FDA scrutiny at sites in the U.S.
  
  
• Routine GMP audits of foreign sites and contractors and thorough quality agreements offer the best protection against compliance issues.
  
  
• While regulatory agencies are working toward globalizing regulatory and quality standards, many countries still have different rules than FDA. Companies should never rely on their foreign firms’ compliance with local standards as a globally-applicable assurance.
  
  
• Warning Letters are not the only possible consequence of noncompliance at an overseas firm. Others can be far more serious. These include Import Alerts, which prevent products from entering the country until FDA is satisfied, and delaying approval of marketing applications if quality issues are found.
  
  
• The number of recent Warning Letters at foreign sites coupled with the fact that FDA’s Office of International Programs is not only well-staffed, but actively inspecting facilities abroad underscores the Agency’s focus on global compliance.

Taking the First Step Toward Better Supplier/GMP Auditing

A closer examination of these recent Warning Letters reveals a line that shows up over and over again: “Consultant Recommended”.

While FDA makes it clear that simply hiring an experienced compliance consultant doesn’t automatically solve the problem, this commonly-repeated advice should be a clear indication that regulators not only see third party consultants as a viable means of remediating compliance issues, but as a solution that has proven itself effective.

When planned and conducted by experienced consultants, GMP audits provide, among other things, extremely thorough assessments of GMP practices––verifying that required systems and controls are in place and in compliance with regulations. This facilitates the early detection of problems and discrepancies before they develop into larger, costlier compliance problems. 

At The FDA Group, we offer a large staff of over 355 consultants––60 of whom are former FDA investigators––to ensure we have the appropriate resource for any auditing project. Our quality professionals perform detailed assessments of your existing quality system, identify current and potential problems, recommend corrective and preventive actions, and work closely with your staff to implement these improvements to your quality system.