Tianjin Kilo Pharmaceutical Sci-tech Co., Ltd. — FDA Warning Letter Findings

Failure to design a documented, ongoing stability testing program to monitor the stability characteristics of APIs and to use the results to confirm the appropriate storage conditions and the retest or expiry dates. Based on the records and information you provided, your firm failed to perform routine stability testing to demonstrate that the quality attributes of your APIs remain acceptable throughout the labeled expiry period. For example, your firm did not provide stability test data for (b)(4) manufactured at your facility. Without an appropriate stability program, you lack adequate scientific evidence to support that your APIs meet established specifications and retain their quality attributes through their labeled expiry period. In response to this letter, provide: A retrospective risk assessment showing how you will ensure that your marketed APIs meet stability specifications throughout their shelf life. A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include but should not be limited to: o Stability indicating methods o Stability studies for each API in its marketed container/closure system before distribution is permitted o An ongoing program in which representative lots of each product are added to the program each year to determine if their shelf-life claim remains valid o A detailed definition of the specific attributes to be tested at each station (time point) o All procedures that describe these and other elements of your remediated stability program Drug Listing Violations Section 510(j) of the FD&C Act and 21 CFR Part 207 set forth the requirements for the listing of drugs. Section 510(j) of the FD&C Act and 21 CFR 207.41 require registrants to list each drug they manufacture for commercial distribution. You did not provide drug listing information for demecarium bromide and chlorambucil under your own labeler code, yet you manufactured and shipped these drugs into the United States. Although these drugs are listed in FDA’s drug listing database, they are listed under a different company’s labeler code, not your own. As the manufacturer distributing these drugs into U.S. commerce, you are required to list them under your own labeler code in accordance with 21 CFR 207.41. Failure to list drugs in accordance with 510(j) of the FD&C Act, 21 U.S.C. 360(j), is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p). Furthermore, under section 502(o) a drug is misbranded if it is not included in a list required by section 510(j). Under section 301(a), the introduction or delivery for introduction into interstate commerce of any drug that is misbranded is prohibited. Complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance. Establishment registration and drug listing information is also widely used outside FDA for purposes such as electronic prescribing and electronic health records, insurance reimbursement, and patient education. It is your responsibility to ensure that all drugs manufactured at your establishment 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. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions.

Failure to prepare and use master production and control records. Your batch record for (b)(4) lacked some of the critical processing information necessary to ensure consistent manufacturing and product quality. For example, you did not list (b)(4) and major equipment used in the manufacturing process. You did not provide a batch record for (b)(4) , despite being asked to provide this documentation multiple times. Without suitable batch records, you cannot adequately monitor and analyze both intra-batch and inter-batch variations to ensure that manufacturing processes remain in a state of control. In response to this letter, provide: A comprehensive, independent global review of the adequacy of the design, control, monitoring, and documentation of the production processes used for all your APIs. Appropriately detailed master batch records that capture all the significant manufacturing steps for each of your APIs.

Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes. Your response to our request for records or other information pursuant to section 704(a)(4) indicates that you manufactured and distributed (b)(4) APIs to the United States (U.S.) without adequate process validation, which is critical to ensure the quality and purity of the API. For example, in response to our request on July 7, 2025, that you provide the process validation summary report for all U.S.-marketed APIs, you indicated that these APIs were still in development and were not commercial products. Therefore, formal documents such as standard operating procedures had not been finalized. However, FDA data shows that your (b)(4) APIs were distributed to 503A compounding pharmacies. Process validation evaluates the soundness of design and 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 determine whether an initial state of control has been established. Without adequate process validation, your firm lacks the basic assurance that you can reproducibly deliver products that meet specifications. See FDA’s guidance document Process Validation: General Principles and Practices at https://www.fda.gov/media/71021/download for general principles and approaches that FDA considers appropriate elements of process validation. In response to this letter, provide the following: A detailed summary of your validation program for ensuring a state of control throughout the product life cycle, along with associated procedures. Describe your program for process performance qualification (PPQ) and the ongoing monitoring of both intra-batch and inter-batch variations to ensure a continuing state of control. A timeline for performing PPQ for each of your marketed drug products. Process performance protocol(s) and written procedures for the qualification of equipment and facilities. A risk assessment and any follow-up actions to be taken for the APIs your firm produced and distributed without first performing any process-validation studies.

Failure to validate and verify the suitability of analytical methods. Based on the records and information you provided, your firm failed to perform test method validation (or verification if compendial testing is used) for each test method used for drugs distributed to the United States. Test methods must be validated to show that they are suitable for their intended use or verified to show, at a minimum, equivalence with United States Pharmacopeia (USP) compendial methods. Method validation and verification are necessary to support reliable determinations of identity, strength, quality, purity, and potency of drugs. Without evaluating the validity of methods, you lack the basic assurance that the data provided to customers were an accurate reflection of pharmaceutical product quality and safety. In response to this letter, provide: A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system. A list of chemical and microbial test methods and specifications used to analyze each lot of your APIs before making decisions about the disposition of a lot, and the associated written procedures.