Cohance Lifesciences Limited

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Cohance Lifesciences Limited, FEI 3008768274, at Plot No. A-19/C, A-23A, A-23B, Road No. 18, IDA Nacharam, Uppal Mandal, Medchal-Malkajgiri, from August 4 to August 12, 2025.

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

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding 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).

We reviewed your September 2, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigator observed specific violations including, but not limited to, the following:

1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm manufactures various (b)(4) dosage forms, including (b)(4) and medications for the treatment of (b)(4). Your investigations into drug-product quality issues were inadequate because they lacked thoroughness, adequate root-cause determination, and appropriate corrective action and preventive action (CAPA). For example, you received a customer complaint about (b)(4) tablets USP (b)(4) mg from two different batches that were reported to be crumbling, disintegrating, pitted, and with dust in the bottle. Your complaint investigation could not identify a root cause and concluded that the complaint was “Not Substantiated.” You noted in your investigation that “the appearance of pitted/crumbly tablets is due to the inherent nature of the raw material ‘(b)(4)’ in the formulation.” Furthermore, your investigation noted two additional complaint investigations for the same issue in three other batches of the same drug product.

In your response, you state that you re-opened this investigation and revised your attributable root cause to your raw material, (b)(4).

Your response is inadequate. Despite identifying a root cause, your response lacks information on chemical testing of reserve samples to confirm that affected tablets meet specifications, and your response does not contain a commitment to perform such testing. Your response lacks remediation for the root cause identified in your re-opened investigation and does not evaluate the quality of your raw materials or consider changes to your formulation to prevent the issue. Additionally, your response fails to consider whether other drug products containing (b)(4) could also be affected.

In response to this letter, provide:

A summary of analytical testing, including dissolution, of reserve samples exhibiting crumbling, disintegrating, pitted (b)(4) tablets USP (b)(4) mg, and an action plan to address this product-quality issue, such as reformulation studies or additional transportation studies.

A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include but not be limited to significant improvements in investigation competencies, scope determination, root-cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root-cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final quality unit decisions, and is fully supported by executive management.

2. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

You failed to adequately clean and maintain your nondedicated drug manufacturing equipment. For example, our investigator observed visible stains within the (b)(4) duct of a (b)(4) (PD/(b)(4)-01) and visible residues on a capsule filling machine (PD/CFM-03) that were documented as clean and had undergone drug product changeover cleaning. Your analytical testing of these stains and residues confirmed the presence of multiple active pharmaceutical ingredients (APIs) with values exceeding your allowable limit.

In your response, you provide investigations into these findings, including a retrospective review of analytical and stability data for all drug products previously manufactured on the pieces of equipment mentioned above. Your investigations attribute the root cause of the cleaning deficiencies to procedural gaps in the cleaning instructions for the (b)(4) and the capsule-filling machine. You state that you plan to revise your cleaning procedures and cleaning checklists.

Your response is inadequate because your review of analytical data and cleaning procedures fails to scientifically demonstrate that your drug products are free of contaminants from the visibly dirty equipment. Your response lacks information about reserve sample testing of drug products released to the U.S. market and within expiry, that were manufactured on these pieces of nondedicated equipment, for cross-contamination potential posed by all previously manufactured drug products.

In response to this letter, provide:

A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated drug products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one drug product.

A CAPA plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning execution for all drug products and equipment; and all other needed remediations.

In addition to this holistic remediation, provide specific CAPA activities that are being undertaken to effectively remediate the conditions that caused the specific cross-contamination incidents discussed above. Provide an independent review by your consultant that determines the effectiveness of your CAPA, including but not limited to:o A list of all enhancements to cleaning and maintenance procedures, including specific frequencies and locations to be cleaned in all relevant equipment (e.g., (b)(4))o Identification of any sources of cross-contamination other than (b)(4) equipment, (b)(4), and ductworko Determination of the adequacy of your analytical methodology to identify residual carryovero Your investigations into any unknown (unidentified) peaks detected in your reserve samples

You have not demonstrated that your cleaning practices are adequate to remove contaminants from the shared equipment used to manufacture multiple drug products. Your 2018 cleaning validation study failed to use the identified worst-case drug product, making it inadequate to ensure cleaning effectiveness. You also did not re-evaluate your cleaning validation program when introducing new drug products on shared manufacturing equipment, and you lack routine cleaning verification. Inadequate removal of drug residues during cleaning can cause cross-contamination in subsequently manufactured drugs on the same equipment.

In your response, you state that the results of your cleaning verification studies from 2019 to 2024 demonstrate that your cleaning processes are effective. You state that you have engaged an independent third-party consultant to review your cleaning validation program and cleaning practices.

Your response is inadequate because your cleaning validation and verification program does not adequately evaluate the effectiveness of your cleaning procedures. Your cleaning verification lacks the ability to detect cross-contamination from carryover.

In response to this letter, provide:

Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst-case in your drug manufacturing operation. This should include but not be limited to identification and evaluation of all worst-case:o Drugs with higher toxicitieso Drugs with higher drug potencieso Drugs of lower solubility in their cleaning solventso Drugs with characteristics that make them difficult to cleano Swabbing locations for areas that are most difficult to cleano Maximum hold times before cleaning

In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new drug product.

A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for drug products, processes, and equipment.

We acknowledge your commitment to temporarily suspend manufacturing and release of drug products from this facility as of August 16, 2025. In response to this letter, clarify when you intend to resume manufacturing of drugs for the U.S. market at this facility.

Before you resume any manufacturing operations regulated under the FD&C Act, notify this office. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.

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.

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

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 re-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 Cohance Lifesciences Limited, FEI 3008768274, at Plot No. A-19/C, A-23A, A-23B, Road No. 18, IDA Nacharam, Uppal Mandal, Medchal-Malkajgiri, 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.1 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 3008768274 and ATTN: Marisa Heayn.