Babikian Healthcare Products CJSC — FDA Warning Letter Findings

Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) & 211.84(d)(2)). Your firm manufactures OTC drug products, including (b)(4) , intended for the U.S. market. Your response to our request for records and information under section 704(a)(4) indicated that you do not test the identity of each incoming component, (b)(4) , used in the manufacture of your drug products prior to manufacturing. Your response also indicated that you accept your suppliers’ certificates of analyses without verifying the test results at appropriate intervals. You also did not provide evidence that (b)(4) , the active ingredients in your drug products, meet USP limits for (b)(4) . See FDA’s guidance document (b)(4) . Without adequate testing and verification of supplier results, you do not have scientific evidence that your incoming components conform to appropriate specifications prior to use in the manufacture of your drugs. As a manufacturer, you have a responsibility to sample, test, and examine incoming materials before use in production to assure adequate quality.

Your firm failed to have, for each batch of drug product, 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. Your firm also failed to conduct appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)). Based on the records and information you provided, you did not demonstrate that you adequately test your finished OTC drug products prior to release and distribution to the United States. For example, the finished product testing reports you provided did not include appropriate assay testing for the identity and strength of each active ingredient or for impurities prior to release. Additionally, the records you provided failed to demonstrate adequate microbiological testing for each batch of your drug product prior to release. Testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all predetermined quality attributes appropriate for their intended use. Drug products must be tested for identity and strength of the active ingredient, prior to release and distribution. Without adequate testing, you do not have scientific evidence to assure that your drug products conform to appropriate specifications before release.

Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22). Based on the records and information you provided, you did not demonstrate that your quality unit (QU) adequately exercised its authority and responsibilities for the manufacture of your OTC drug products. For example, your QU failed to ensure the following: Establishing appropriate written procedures for production and process controls to qualify process performance and for qualification of your (b)(4) system, which produces (b)(4) used as a component in your drug products (21 CFR 211.100(a)). Maintaining complete manufacturing information relating to the production and control in batch records (21 CFR 211.188). Providing appropriate stability data to support the labeled drug product expiration date (21 CFR 211.137(a)). Establishing adequate QU authority and procedures (21 CFR 211.22(a) & 211.22(d)). Your firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA guidance documents Quality Systems Approach to Pharmaceuticals CGMP Regulations at https://www.fda.gov/media/71023/download. Drug Registration and Listing We note that two separate establishments are referenced in this warning letter. Under section 510(i) of the FD&C Act and 21 CFR 207.17(a) any establishment within any foreign country engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is imported or offered for import into the United States must be registered with FDA. Under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), it is a prohibited act to fail to register an establishment as required by section 510 of the FD&C Act. Additionally, a drug may be considered misbranded within the meaning of section 502(o) of the FD&C Act, 21 U.S.C. 352(o) if it was manufactured in an establishment not duly registered under section 510 of the FD&C Act. It is your responsibility to ensure that all drugs manufactured at your establishment(s) comply with all establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations. CGMP Consultant Based upon the nature of the violations we identified in your response, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.