GMP Violations Continue to be Cited in Warning Letters
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FDA continues to issue more warning letters to companies that do not adequately respond to 483 violations.
The violations and 483 responses provide excellent learning opportunities. Here are some key takeaways.
● Documentation. This is a rather embarrassing reminder that FDA can look at any controlled document. “If it’s not written down, it didn’t happen” is a vital part of GMPs.
→ From warning letter. “The tablet run sheet for … includes out of specification fill weights… The tablet run sheet has weights throughout in the range and notes “tablet won’t hit the weight so running.” A corrective action approved by the firm’s quality unit was not documented.”
● Common (major) allergen disclosure. When disclosing the major allergens fish, crustaceans, or tree nuts (most cases), the specific type should be disclosed, such as “Contains fish (tuna).” I remember when the FALCPA was enacted in 2004, my third year as a supplement manufacturer.
→ From warning letter. “the finished product labels fail to declare the major food allergen, shrimp and crab, as required by section 403(w)(1) of the Act. Specifically, as you have chosen to use a “Contains” statement, you must declare the specific type of Crustacean shellfish.”
● Herb common names. The American Herbal Products Association (AHPA) Herbs of Commerce book is the FDA-recognized way to list the common names of herbs. This book is essential for supplement companies and consultants.
→ From warning letter. “Your … Facts label declares the … but fails to state the standardized common name “(b)(4)” as listed in the reference Herbs of Commerce, as incorporated by 21 CFR 101.4(h).”
● Finished product composition. This has been showing up in more warning letters and 483s and is a rigid interpretation of the finished product composition requirements. Let’s say there is a blend of herbal ingredients that have been tested for identity and purity. If they are blended with a validated procedure and encapsulated, FDA requires a company to prove composition in the finished product even if there are no specific constituents, such as curcuminoid content, to test. It is my understanding FDA has been encouraging companies to develop expensive finished product composition tests to verify this. This is a new and burdensome enforcement trend to watch.
→ From warning letter. “The input of the various dietary ingredients during production and subsequent analysis of a single dietary ingredient alone in the finished product is not sufficient to verify specifications for identity, purity, strength, and composition in a finished product because inputting specific amounts of various ingredients during manufacturing does not ensure that specifications are met in the finished product, nor does later testing for a single dietary ingredient assess any other components within the finished product.”
Adverse event reporting address on labels. A domestic street address or phone number is required on labels which is an essential aspect of dietary supplement safety. An email, website, or QR code is not sufficient.
→ From warning letter. “Your product label is misbranded within the meaning of section 403(y) of the Act [21 USC § 343(y)] in that the label fails to bear a domestic address or domestic phone number through which the responsible person (as described in section 761 of the Act) may receive a report of a serious adverse event with such dietary supplement.”
Read the full warning letter here. The 483 responses are humorous.
Disclaimer: The educational information provided here is for informational purposes only. Contact an attorney for specific legal advice. Rule #1 in compliance is to ensure marketing is truthful and not misleading.