FDA Issues Warning Letter to Vietnamese Drug Manufacturer for CGMP Violations

The U.S. Food and Drug Administration (FDA) issued a Warning Letter to a drug manufacturing facility in Vietnam following an inspection conducted in December 2023, that uncovered significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. The document dated 05 June 2024 was published on the FDA's website on 23 July 2024.

Testing and Release for Distribution

21 CFR 211.165(a) states:

• "For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. [...]"

In this regard, the FDA found the following violations:

• The company released drug products without adequate quality control testing. For example, identity and potency testing was not performed for the active ingredient.
• Testing does not establish comparability to United States Pharmacopeia (USP) standards.

Testing and Approval or Rejection of Components

As per 21 CFR 211.84(d)(2),

• "each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

In this context, the FDA criticises:

• The company failed to perform adequate identity testing on each lot.
• By doing so, the firm especially failed to assure the acceptability of ethyl alcohol and benzylkonium chloride for use in the manufacture of the drug products.

Expiration Dating

21 CFR 211.137(a) requires the following:

• To assure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use, it shall bear an expiration date determined by appropriate stability testing described in § 211.166.

The FDA writes the following:

• The company assigned a three-year expiry period to the product without scientific rationale to support the labeled expiry.
• Data to demonstrate that chemical and microbiological properties of the drug products will remain within specification throughout their labeled expiry period could not be provided.

Responsibilities of Quality Control Unit

The fourth main point refers to 21 CFR 211.22, which says:

• "(a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.
• (b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.
• (c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.
• (d) The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed."

The FDA now subsumes a whole series of deficiencies under this paragraph, namely the following QU failures:

• "Adequate validation of manufacturing processes for ethyl alcohol antiseptic wipes (21 CFR 211.100(a)).
• Adequate cleaning validation for equipment used in the manufacture of ethyl alcohol antiseptic wipes (21 CFR 211.67(b)).
• Adequate storage and retention of CGMP records (21 CFR 211.180(a)).
• Adequate collection and storage of reserve samples (21 CFR 211.170(a))."

Conclusion

The FDA has demanded comprehensive corrective actions and warned of potential consequences, such as withholding approval of new applications or detaining products at U.S. borders if compliance is not achieved. The company has 15 working days to respond with a detailed plan addressing these violations and preventing future occurrences.

For more details, please read the Warning Letter to Yahon Enterprise Co., Ltd. on the FDA's website.