Somerset Therapeutics Private Limited

Warning Letter 320-25-106

September 4, 2025Dear Mr. Subramanian:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Somerset Therapeutics Private Limited, FEI 3003821988, located at 54/1 Budihal (Boodihal) Village, Nelamangala, Bengaluru, Karnataka, India, from February 10 to 21, 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).

The inspection also revealed that Somerset Therapeutics Private Limited failed to submit (b)(4) Field Alert Report (FAR) to FDA as required by section 505(k) of the FD&C Act 21 U.S.C. 355(k), 21 CFR 314.81(b)(1) (NDA), (b)(4).

We reviewed your March 14, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigators 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).

You failed to conduct adequate investigations. Investigations lacked data supporting the assigned root cause(s), were not adequately expanded to include all potentially affected drug products, or were not formally documented in your deviation system. Specifically:

A. Your firm did not adequately investigate extensive contamination in a September 2024 media fill failure on the (b)(4) filling line. Notably, the contamination was visible to the human eye coming off the line before incubation.

Your investigation identified the cause of the media fill failure as a breach in the (b)(4) tank (b)(4) tubing and indicated that the contamination may have occurred due to operator activities.

Your investigation also identified your ampoule filling line as having a similar equipment configuration to the (b)(4) filling line and indicated that the ampoule filling line is susceptible to the same failure mode. The investigation noted, “Over the past 2 years, no tubing damage was ever observed in the product pathway which can be readily detected in the form of leakage. Hence, a very low risk is anticipated for previously filled and completed product batches.” You did not sufficiently address the detectability of this defect or the possibility of a similar event going undetected on the ampoule filling line. You also did not adequately address contamination risks posed by vessel changeovers, nor ensure timely elimination of the use of unnecessary tubing to connect (b)(4) to (b)(4) vessels.

We also note that your (b)(4) filling line was used to fill (b)(4) sterilized drug products. Regarding the (b)(4) batches of (b)(4) sterilized drug products produced since the previous successful media fill on May 29, 2024, your investigation stated that there was “… [no] impact and no action required” and that the (b)(4) sterilization cycles were “… validated using an overkill approach.” However, you failed to adequately consider the potential for high levels of contamination and the susceptibility of the isolated spore-forming organism (Bacillus cereus) to the sterilization process.

B. You failed to adequately investigate out-of-specification (OOS) results for “any individual unspecified impurity” during related compound analysis of (b)(4) injection validation batches and an (b)(4) solution commercial batch. You identified the unspecified impurity in these drug products to be associated with an individual active pharmaceutical ingredient (API) lot used to manufacture the drug products, which exhibited a different impurity profile during the drug product shelf life when compared to exhibit batches. The investigation lacked adequate information on the root cause of the API impurity, and you did not ensure a timely response to assess the risks to other finished product batches potentially affected by the API from this supplier.

C. You failed to review electronic data from (b)(4) air samplers used for environmental monitoring and ensure a timely and appropriate investigation of numerous aborted air sampler events. During the inspection, we identified at least 16 aborted air samples collected over (b)(4) in February 2025, within the (b)(4) areas and corridors. The review of aborted air sampler data was limited by its unacceptable data retention capability of only 115 entries.

Your response is inadequate. You state that the “(b)(4)” of the (b)(4) organisms used to validate your (b)(4) sterilization cycle is greater than the “(b)(4)” of the B. cereus organisms identified in the contaminated media. Although B. cereus is typically known to exhibit less (b)(4) than (b)(4), B. cereus is also known to have a relatively wide range of (b)(4), with some strains exhibiting significant (b)(4).1 Your response did not indicate plans to evaluate the susceptibility of specific contaminating organisms found in media used to simulate drug products and drug products prior to sterilization against your (b)(4) sterilization process in the future.

You note in your response, “… (b)(4) of the (b)(4) vessels, their tubing, the manifold, and (b)(4) tubing had already been decontaminated and (b)(4). The (b)(4) vessel (ID# PDN/(b)(4)/1264) and the (b)(4) tank (ID# PDN/(b)(4)/574) which had been used to fill the (b)(4) of vials had not yet been decontaminated and (b)(4).” You failed to adequately maintain the equipment, thereby limiting your ability to ensure investigation and determination of the true root cause of the failure.

Your response acknowledges a significant adverse trend of B. cereus contamination in your facility at the time of the media fill failure and that the route of contamination may involve employee changing rooms. Notably, you also indicate that (b)(4) airborne microbial monitoring is conducted in change rooms “For Information” only. Your response does not propose a systemic review and CAPA to address your environmental monitoring program.

Your response provides an extended investigation into the impurities in the (b)(4) drug products. While you collaborated with your API supplier to identify the impurities and establish new specifications, adequate CAPA activities were completed only after the inspection identified the deficiency. Your response fails to include provisions for improving ongoing lifecycle oversight of suppliers.

We acknowledge your statement that your (b)(4) air samplers are now compliant with applicable data control requirements and that you evaluated the available electronic data. However, the investigation into the aborted air samples was severely limited because of irretrievable data, resulting in an uncertain assessment of the acceptability of the environment for many marketed batches.

In response to this letter, provide:

A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, 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.

A further investigation into the (b)(4) media fill failure that examines all potential contributing causes and includes CAPA to address them.

An independent, comprehensive assessment of microbiological contamination risk for all distributed drug products and batches remaining within expiry that were manufactured on the (b)(4) and ampoule lines using (b)(4) tubing for (b)(4) assemblies on (b)(4) tanks.

Your program to assess (b)(4) of spore-forming microorganisms identified in product bioburden and the manufacturing environment for (b)(4) sterilized drug products.

A comprehensive, independent review of your personnel and environmental monitoring programs, including but not limited to a plan to fully remediate these programs. For example, describe changes to procedures, practices, and testing equipment that will ensure meaningful ongoing data is collected to promptly detect and respond to emerging risks in your classified areas. Provide a timeline for implementation of your remediated program, including a summary of the steps you will be undertaking to ensure CAPA effectiveness.

An evaluation of the source of the (b)(4) API impurity, including CAPA that address the need to develop full impurity profiles for your supplier’s APIs.

A comprehensive assessment of your air samplers and how you will ensure data will be retained and reviewed. Also provide an update on your impact assessment relating to the lost data.

A comprehensive, independent assessment of electronic and paper-based documentation systems in manufacturing and laboratory operations, to identify insufficient documentation practices. Include a detailed CAPA plan to remediate data review practices and to ensure attributable, legible, complete, original, accurate, contemporaneous records.

A comprehensive, independent assessment and CAPA plan for computer-system security and integrity. Include a report identifying design and control vulnerabilities and the appropriate remediations for each of your laboratory and manufacturing computer systems.

Clarify whether you will continue to use (b)(4) suppliers of (b)(4) API, and what standards will be required of these suppliers, including but not limited to, impurities.

On February 11, 2025, we observed that tape was being used to secure (b)(4) to the interior ceiling of the (b)(4) filling line ISO 5 (Grade A) space. This tape was detached in multiple locations during the aseptic manufacture of (b)(4) injection, USP (b)(4) mg/mL ((b)(4) mL), batch (b)(4). Your decision to use tape in a critical area to overcome a cleanroom deficiency raises significant concerns about your oversight of the adequacy of your facilities for aseptic processing. The detached tape may disrupt airflow within the ISO 5 space, is insanitary, cannot be cleaned, and has an adhesive side that can collect particulate contaminants. You subsequently performed airflow (smoke) studies within the ISO 5 space in an effort to assess the effect of the detached tape on airflows. You also performed surface sampling of the exposed adhesive side of the detached tape, which was intended to detect any microbiological contamination.

Your response is inadequate. You reported that multiple personnel, working in and around the (b)(4) filling line on February 1-2 and 6-7, 2025, did not notice any abnormalities. You therefore estimated that the tape detachment started between February 7 and 11, 2025. Your personnel reportedly did not observe detached tape while working in the area in the days preceding the FDA inspection. However, you did not conclusively show that the equipment was suitable for the aseptic manufacture of sterile drugs before FDA observed this deficiency during the inspection. Your response also did not include an investigation explaining why multiple segments of the tape became detached. You did not establish that (b)(4) injection, USP (b)(4) mg/mL ((b)(4) mL), batch (b)(4), was the only product manufactured under these conditions. The subsequent smoke studies and use of (b)(4) plates to perform microbiological sampling do not justify the existence of insanitary surfaces over exposed sterile drugs on an aseptic processing line.

In response to this letter, provide:

Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.

An amended investigation into the detached tape issue that evaluates all drug products and batches manufactured under this adverse condition, identifies the root cause(s), and includes your CAPA to address the root cause(s).

3. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

We observed multiple significant risks to product sterility during your aseptic manufacturing operations.

Interventions

Some interventions were not adequately designed to prevent the risk of contamination. For example, operators use (b)(4) Restricted Access Barrier System ((b)(4)RABS) (b)(4) on the (b)(4) line to transfer materials to and from the ISO 5 area. You identify these interventions in the ISO 5 area as “(b)(4)” interventions, despite personnel (b)(4) the ISO 5 area with their hands and arms to perform various activities. Poor aseptic behaviors associated with the use of similar (b)(4)RABS (b)(4) on the (b)(4) line were previously discussed in the October 6, 2022, regulatory meeting between your firm and FDA.

Material Transfers

Material transfers were also deficient. For example, FDA observed that one of the (b)(4)RABS (b)(4) was being (b)(4) for extended periods of time to facilitate the transfer of sterilized stopper bags to the ISO 5 area on the (b)(4) filling line.

Airflow Studies

Airflow studies did not allow for adequate identification and evaluation of aseptic processing hazards. For example, a video recording of the airflow study performed on the (b)(4) line did not include the removal of vials between the (b)(4) vial (b)(4) and the filling machine. There was significant activity in the area where the operator was performing this manual intervention.

Additionally, the video of an airflow study performed for the (b)(4) adjustment did not allow for adequate analysis of potential hazard(s) posed by the intervention. The study did not sufficiently visualize smoke in the vicinity of the intervention.

Your response is inadequate. You do not commit to sufficient review of aseptic processing line design, including the hazards posed by use of the (b)(4)RABS (b)(4) (e.g., the (b)(4)) to perform interventions.

Although you supplied a third-party report indicating that the videos were adequate, the report does not address the sufficiency of airflow visualization at the point of these interventions. You also state, “During (b)(4) intervention within the filling zone (between the sensors) in (b)(4) Line, all the containers (i.e., bottles/vials) exposed from start of filling zone until stoppering zone are rejected….” However, you do not adequately address the hazard posed to empty vials on the filling line immediately adjacent to the filling zone, where airflow was interrupted during the intervention.

We acknowledge your commitment to revise the stopper bag addition procedure to require (b)(4) the barrier system (b)(4) bag sanitizations. You further commit to modifying the (b)(4) design and incorporating the use of an (b)(4) to transfer sterilized stopper bags into the (b)(4). However, the modifications to equipment and processes are insufficient to fully address the manual hazards associated with your process design. You also do not adequately address the conditions under which, and maximum length of time, barrier system (b)(4).

In response to this letter, provide:

Comprehensive risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including an independent assessment that includes but is not limited to:o All human interactions within the ISO 5 areao Equipment placement and ergonomicso Air quality in the ISO 5 area and the surrounding roomo Facility layouto Personnel Flows and Material Flows (throughout all rooms used to conduct and support sterile operations)o Maximum in-process hold times and batch processing times

A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to aseptic processing operation design and control.

Your plan to reevaluate interventions performed in airflow studies and media fills, to ensure that they appropriately reflect those taking place during commercial manufacturing operations (e.g., specific activities, duration).

Your plan to conduct new airflow studies, by or with the assistance of one or more qualified independent third parties. Your plan should include a qualified independent third-party assessment of the airflow studies.

Your plan to provide training for relevant personnel on the conduct and interpretation of airflow studies, to be conducted by one or more qualified third parties.

The NDA/ANDA Field Alert reporting requirements in 21 CFR 314.81(b)(1)(ii), effective since May 23, 1985, require holders of NDAs and ANDAs to submit information concerning any bacteriological contamination, or any significant chemical, physical, or other change or deterioration in the distributed drug product, to the appropriate FDA district office within three working days of receipt by the applicant. The intent of the 21 CFR 314.81(b)(1) regulation is to establish an early warning system so that significant problems are brought to the FDA’s attention by applicant holders in order to prevent potential safety hazards from drug products already in distribution and also to prevent potential safety hazards with drug products manufactured in the future. FARs must be submitted for confirmed and unconfirmed problems meeting the definition of the regulation within three working days of becoming aware of the problem.

From this inspection, in addition to the aforementioned CGMP violations, your firm is in violation of the Field Alert reporting requirements set forth in 21 CFR 314.81(b)(1)(ii). FARs related to a September 2024 aseptic processing simulation (media fill) failure were not provided to FDA within three working days. Specifically, you identified visually cloudy vials among the filled vials around September 30, 2024. No FAR was submitted until after the close of this inspection.

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 drug 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 Somerset Therapeutics Private Limited, located at Budihal (Boodihal) Village, 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 days2. 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 3003821988 and ATTN: Jason Chancey and Vilmary Negrón Rodríguez.