Respilon Production S.R.O. — 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) and 211.84(d)(2)). Your response to our request for records under section 704(a)(4) indicated that you do not test the identity of each incoming component used in the manufacture of your drug products, such as (b)(4)…

Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (211.194(a)). Your response to our request for records under section 704(a)(4) indicated that your finished drug product’s Certificate of Analysis did not provide an individual test result for (b)(4) content. The “Batch Production” record that you provided as your Certificate of Analysis states “PASSED” in the “Conformity” section but does not provide an assay result. CGMP Consultant Recommended Based upon the nature of the violations we identified at your firm, 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 audit1 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 firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)). Your response to our request for records under section 704(a)(4) indicated that you have not performed stability studies for the OTC drug products you manufacture, despite your drug product’s displaying an expiration date on the label. Without the appropriate stability studies, you do not have scientific evidence to support whether your drug product’s active ingredient maintains its strength, purity, and quality throughout the shelf life of the product.

Your firm failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)). Your response to our request for records under section 704(a)(4) indicated that you failed to adequately validate the test method used to analyze raw materials and finished drug products. Method validation or verification has not been completed for the active ingredient assay testing for (b)(4) . Your analytical method does not…

Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)). Your response to our request for records under section 704(a)(4) indicated that you failed to adequately validate your drug manufacturing processes to demonstrate that they are reproducible and controlled. Process validation evaluates the soundness of design and the state of control of a process throughout its life cycle. Each significant stage of a manufacturing process must be designed appropriately and must ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and to evaluate batches to determine whether an initial state of control has been established.