USV Private Limited

This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility and provides you an opportunity to address them. Promptly address any violations described herein without delay, including ensuring that appropriate resources are allocated to fully address them and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address any violations may result in regulatory action without further notice.

Violations were observed and documented during an inspection of your drug manufacturing facility, USV Private Limited, FDA Establishment Identifier (FEI) 3004086192, at H-13, 16, 16a, 17, 18, 19, 20, 21 & E-22, OIDC Mahatma Gandhi Udyog Nagar, Dabhel, Daman, Dadra and Nagar Haveli and Dam, from April 7 to 17, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.

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 May 8, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

1. 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)).

Your firm manufactures aseptically filled parenteral (b)(4) drug products. You failed to implement appropriate processes and systems to assure an ongoing state of control of your aseptic processing operations.

You aseptically manufacture injectable products using a (b)(4) approach, with (b)(4). In addition, your (b)(4) filling line included (b)(4) and was intended as a restricted access barrier system (RABS) but had significant design deficiencies.

Your airflow visualization studies (i.e., smoke studies) performed for the ISO 5 vial filling line did not exhibit unidirectional airflow throughout the ISO 5 area. This lack of unidirectional airflow poses a significant risk to drug product sterility. For example, airflow was observed to swirl and move upward. Additionally, your smoke studies did not adequately evaluate airflow at ISO 5 to ISO 7 transition interfaces.

We also observed poor aseptic technique during (b)(4) interventions on your (b)(4) filling lines. For example, operators breached first air by extending their forearms over sterile equipment. Additionally, there was inadequate control of material flow from ISO 7 to ISO 5 areas.

In your response, you acknowledge deficiencies in your aseptic practices and airflow visualization studies. You add that you engaged an independent consultant to advise on these areas. However, your retrospective risk assessment concluded that the process was in a state of control, citing “no growth” (b)(4) monitoring and compliant environmental monitoring for the (b)(4) filling line. You also cite compliant sterility and bacterial endotoxin results for the vial filling line, and passing media fills for (b)(4) lines.

Your response is inadequate. The aseptic processing operations have fundamental flaws in design leading to unidirectional airflow deficiencies, poor ergonomics, and deficient aseptic practices. Such inherent flaws cannot be validated and necessitate redesign. While you engaged consultants for specific aspects of your process design and smoke study program, you lack sufficient commitment to comprehensively remediate your aseptic processing operations, supported by a complete assessment of your aseptic processing operation and equipment replacement. Your risk assessment relies on proxy indicators such as sterility results, media fill pass rates, and environmental monitoring data without systematically addressing deficiencies in the design and control of your operation.

The ISO 5 area is critical because sterile products are exposed and therefore vulnerable to contamination. Your aseptic manufacturing process should be designed, and operations executed to prevent contamination hazards to your sterile product.

In your response to this letter, provide:

Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to an independent assessment of the following with accompanying corrective action and preventive action (CAPA):o Suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing operationso Deficiencies in production management oversight, and identification of specific improvements to ensure effective and routine supervisory oversight for all batcheso Frequency and depth of quality unit (QU) oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operationso Adequacy of written procedures and operational ergonomicso The assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs

Describe whether all personnel performing activities that take place in ISO 5 areas are held to ISO 5 personnel monitoring standards

2. Your firm failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups. Your firm also failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance. (21 CFR 211.42(c) and 21 CFR 211.63).

Your facilities and equipment are not adequately designed to protect sterile drugs from significant contamination risks. In addition to areas of deficiency described in the first violation in this letter, other examples include:

The (b)(4) filling line's (b)(4) conveyor system physically blocked continuous ISO 5 unidirectional airflow from reaching open sterile bottles during transport to the filling station.

Critical areas used for aseptic connections, sterile component unwrapping, and material transfers were insufficient to assure maintenance of ISO 5 conditions.Significant turbulence was observed in your vial filling line airflow visualization videos. However, your firm concluded that airflow was adequate.

Your initial response indicates that you suspended production on the (b)(4) line, pending engineering assessment and remediation. However, your remediations are minor and narrow in scope. Your response is inadequate because it fails to address the need for comprehensive remediation across your aseptic processing operations.

In your response to this letter, provide:

Comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to:o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of (b)(4) interventions wherever possible)o Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficient cleanroom spaceo Air quality in the ISO 5 area and surrounding room including, but not limited to, air volume and flowo Facility layouto Personnel Flow and Material Flow (movement throughout all rooms used to conduct and support sterile operations, and all material transfers)o Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessmento 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 at your facility and explain how this CAPA plan will robustly remediate your deficient sterile manufacturing operations. Include comprehensive changes to the design of both your aseptic processing lines and cleanrooms. Also, describe your plans for qualification and validation of your extensively remediated operations.o Also describe your contingency plans in the event your supply chain continuity may be compromised (e.g., stockpiling inventory using interim manufacturing controls, and/or utilizing contract manufacturing organizations).

An independent, comprehensive evaluation of airflow unidirectionality in your aseptic processing operations. Ensure smoke studies are conducted under dynamic conditions with thorough and complete evaluations of aseptic processing line airflow unidirectionality, including special emphasis on the impact of aseptic interventions and dynamic interactions with the surrounding cleanroom. Conduct these smoke studies after you remediate your aseptic operation and using proper practices (e.g., neutrally buoyant media) to appropriately visualize airflow.

For your aseptic processing rooms, provide detailed description of the current location of each air return, including but not limited to any located on or near the ceiling. Describe in detail the air flow dynamics at each return and provide any related smoke studies.

Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should incorporate oversight from a qualified independent consultant and 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 senior management review. Your plan should also ensure that appropriate actions are taken throughout the company network.

3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

Your visual inspection program was inadequate to assure your drug products were essentially free of visible particulates.

Lack of Alert and Action Limits

You lacked action limits for visible particulates. You also only defined alert limits for certain particulate types in selected presentations of your (b)(4) injection drug products. Your visual inspection procedure requires the investigation of atypical trends, yet you failed to investigate atypical trends in (b)(4) injection batch (b)(4). Without well-defined metrics to characterize acceptable process performance, including but not limited to alert and action limits, it is difficult to reliably detect when a process has deviated from a state of control.

Lack of Extrinsic and Intrinsic Particulate Classification

You did not classify particulates as extrinsic or intrinsic. However, your procedures state that extrinsic particulates indicating filth, sterility assurance issues, or CGMP violations are unacceptable irrespective of statistical sampling acceptance criteria. Your failure to classify extrinsic particles from your batches can lead to not detecting critical quality and safety risks.

Prior to March 28, 2026, you also released all batches of (b)(4) without adequate visible particulate assessment.

In your response, you commit to establish alert and action limits for all products. You also commit to implement intrinsic and extrinsic particulate classifications, and a destructive testing program for (b)(4) containers (such as those used for (b)(4). You state that retrospective destructive testing of (b)(4) batches within expiry did not detect any particles.

Your response is inadequate. It does not address your failure to follow your own procedures on batch disposition criteria for extrinsic particles for products already distributed. Moreover, retrospective destructive testing and assessments of flawed visual inspection data cannot substitute for the required characterization and control you lacked at the time of production.

In response to this letter, provide:

Raw data and tabulated summary of your retrospective destructive testing results

An independent, comprehensive assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The remediation plan should incorporate USP <790> Visible Particulates in Injections (b)(4), including container-specific testing protocols (e.g., (b)(4) containers) for each container type. Your strategy should include:o For all products, assess the suitability of all specifications, alert and action limits, sampling methods, test methods, and validation for visible particulate inspection, subvisible particulate inspection, as well as any supplemental destructive tests, to determine if they are sufficient to support batch disposition decisions. The assessment should also identify appropriate CAPAs, including these elements: Enhancements to your 100% visible particulate inspection practices to improve detectability and reliability Robust methods, equipment, and personnel qualifications to reproducibly detect visible particulates Rigorous qualification studies to ensure your (b)(4) visible particulate inspection systems consistently and reproducibly detect the variety of visible particulates encountered in your drug products Review past history to develop a product-specific, risk-based visual inspection approach incorporating product knowledge, process experience, deviation investigation analysis, historical data on particle contaminants and sources, and recall/complaint data to ensure ongoing compliance with USP <790>, (b)(4), and CGMP requirementso If you manufacture difficult-to-inspect products (e.g., (b)(4) containers), address these elements and provide a CAPA: 100% visible inspection using enhanced lighting with background contrast methods, as appropriate (e.g., (b)(4) containers (b)(4)) that optimize visual inspection Identify provisions for highly capable supplemental destructive testing and/or use of advanced technologies (e.g., (b)(4)), as appropriate, with statistically significant sample sizes to test for critical defects.o If you manufacture drug products that preclude visual particulate inspection (e.g., products packaged in (b)(4) containers), address these elements and provide a CAPA: Highly capable destructive testing method(s), with appropriate, statistically significant sample sizes to test for particulates.o In each case, whenever visual inspection methods are insufficient or cannot be used, also implement enhanced upstream particulate controls (e.g., in-process (b)(4), environmental controls, protective design provisions, robust container/closure supplier oversight). This should also generally include appropriate in-process visible particulate matter testing at (b)(4) stage.o A risk assessment of all previously released batches currently within expiry that were released without adequate evaluation of particulate contamination.

A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, action level results (out of limits), 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, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

A comprehensive assessment and remediation plan to ensure your QU is given the authority, independence, and resources to effectively function that includes, but is not limited to:o A determination of whether procedures used by your firm are robust and appropriateo Provisions for independent QU oversight throughout your operations to ensure satisfactory procedures and adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decisiono Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productso Also, describe how executive management will support robust quality assurance at your firm, including but not limited to timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control

We encourage the use of suitable (b)(4) visual inspection for particulates to augment the (b)(4) visual inspection program. (b)(4) methods should be rigorously studied, and qualified, to assess their capability and robustness under various conditions, machine settings, container-closure sizes, defect types, product characteristic, and other variables. In addition, any use of (b)(4) particulate inspection as an adjunct method does not supplant the need for (b)(4) visual inspection for various other attributes (e.g., cracks, deformities, closure issues, volume, insufficient (b)(4), leaks, (b)(4), discoloration, turbidity, other appearance defects).

It is important that any visible particulate contamination is appropriately evaluated and investigated. Visible particulates in injectable products should be avoided through appropriate preventive measures built into your design and production controls. When categorizing any visible particles, extrinsic or foreign matter should receive special attention, as it may indicate possible microbial contamination. Extrinsic or foreign particulate contamination should occur very infrequently, and trigger a thorough investigation and appropriate CAPA.

(b)(4) product operations should be designed to prevent particle contamination. Regarding (b)(4) products, it is essential that operations are designed and controlled to protect consumers from the risk of (b)(4) potentially harmful particles (b)(4). Microbes introduced (b)(4) can pose a serious risk to consumers. Irreversible damage, including (b)(4), can occur and, in some cases, may progress to life-threatening systemic infection.

See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.

Your firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidances: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download, and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download.

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

We acknowledge your initial commitment to suspend production of your (b)(4) drugs at this facility for the U.S. market. You subsequently notified us of your decision to discontinue commercial manufacturing of product from the (b)(4) filling line to the U.S. market. In response to this letter, clarify whether you intend to resume manufacturing (b)(4) drugs for the U.S. market at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, 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 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 all corrective action and preventive action, before you pursue resolution of your firm’s compliance status with FDA.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

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 USV Private Limited, Dabhel, Daman, Dadra and Nagar Haveli and Dam, India, 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).

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.

If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.

FDA posts warning letters to www.FDA.gov.