Respilon Production S.R.O.

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our May 2, 2025, request and subsequent correspondence, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Respilon Production S.R.O, FEI 3018892481, at Prikop 843/4, Brno, Jihomoravsky, Czech Republic.

This Warning Letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21, Code of Federal Regulations, parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)).

Following our review of records and other information you provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including but not limited to, the following:

1. 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), before manufacturing.

In addition, you failed to test each shipment of (b)(4) for (b)(4) contamination before use. Identity testing for (b)(4) and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of (b)(4). Because you did not perform adequate identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to ensure the acceptability of these components for use in the manufacturing of your drug product. See FDA’s guidance document (b)(4) for help in meeting the CGMP requirements when manufacturing drugs containing ingredients at high risk for (b)(4) contamination.

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.

3. 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.

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 demonstrate specificity, accuracy, precision, and robustness. Additionally, it appears that your firm is not performing microbiological testing for each batch of your drug products before release. In your response, you state that your drug product has low (b)(4) at less than (b)(4) and that microbial proliferation is not possible. However, you have not validated your overall manufacturing process or conducted stability studies to determine if microbial contamination proliferates throughout the shelf life of the product. You have not provided a comprehensive microbial risk assessment of your manufacturing steps, such as in-process hold times, storage conditions, and the microbial load of your (b)(4) ingredients. The statement in your response that you intend to conduct reduced microbial testing is insufficient, based on the limited information you provided and the lack of documentation to support your approach.

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.

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.

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA refusing admission of articles manufactured at Respilon Production S.R.O., Prikop 843/4, Brno, Jihomoravsky, Czech Republic into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3018892481 and ATTN: Erika V. Butler.