The following specific deviations were observed during the inspection:

1. Failure to have appropriate procedures (or practices) in place to prevent cross contamination.

2. Failure of your quality unit to exercise its responsibility to ensure the APIs manufactured are in compliance with CGMP, and meet established specifications for quality and purity.

3. Failure to thoroughly investigate all Out-of-Specification (OOS) results.

4. Failure to monitor cleaning procedures, after validation, to ensure effectiveness.

The warning letter is quoting the the Federal Food, Drug, and Cosmetic Act (Section 501 (a)(2)(B); 21 U.S.C. §351(a)(2)(B))

SEC. 501. [21 USC §351] Adulterated Drugs and Devices

"A drug or device shall be deemed to be adulterated [...]
(a)(2)(B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess;"

OUTCOME

If you are a producer of APIs review your self inspection reports to be sure that they cover the above listed observations. If you notice gaps in your procedures start a project to improve your quality system.

If you are a pharmaceutical manufacturer be sure to inspect all your API suppliers. Prepare checklists to cover all relevant and critical aspects.

You find a lot of material that help to prevent such a warning letter in the GMP MANUAL including a comprehensive audit checklist.

Link to API Warning Letter

Source: FDA Warning Letters Website

Editor: Thomas Peither, Maas & Peither AG / Halfmann Goetsch Peither AG