Tentamus India Private Limited

The United States Food and Drug Administration (FDA) inspected your contract testing laboratory, Tentamus India Private Limited, FEI 3010960741, at 3-31/33, Part Sy. No. 123, 124,125 & 142, Kompally, Quthbullapur, Hyderabad, Telangana State, from August 14 to 22, 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, the drug products you tested 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).

Furthermore, during the inspection you delayed or limited access to records requested. Due to your delay and limiting access to records during the inspection, the drug products you tested are also deemed adulterated within the meaning of section 501(j) of the FD&C Act, 21 U.S.C. 351(j).

We reviewed your September 15, 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’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your quality unit (QU) failed to ensure that all CGMP records were retained and available for review. Our investigator discovered two garbage bags containing torn analytical records, including chromatographic results, unidentified number lists, and impurity method validation spreadsheets with handwritten notes. For the method validation study, official records contained only handwritten values, while the original data was discarded in the garbage bags. This practice violated your lab documentation standard operating procedure (SOP) which prohibits destroying records or instrument printouts due to errors and requires filing such documents with original data for traceability with proper justification.

Additionally, laboratory staff used unofficial personal diaries to record procedures, analytical observations, results, method modifications, and deviation descriptions. Your firm lacked procedures to control the use of these personal diaries and to ensure proper retention of all CGMP data.

In your response, you state you opened an investigation and that the validation documents in the garbage bags were not related to drug products destined for the United States. Your response is inadequate. Irrespective of the ultimate use or intended purpose of the validation documents, because your firm operates with a single set of procedures, equipment, and practices for all products tested at your facility, including those destined for the United States, all testing and data must be handled appropriately and in accordance with established procedures. Furthermore, your response fails to describe immediate corrective actions to prevent the destruction of CGMP data or to prevent the use of unofficial diaries to record CGMP data.

Reliability of data is compromised when there is a failure to maintain complete records of the conditions and data associated with all tests. Furthermore, the lack of complete data compromises the QU’s ability to exercise its function of ensuring compliance to applicable standards.

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you test. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP: Questions and Answers for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

We acknowledge that you are using multiple independent third-party consultants to audit your operations and assist in meeting FDA requirements.

In response to this letter, provide:

A comprehensive investigation into the extent of the inaccuracies and omissions in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third-party.o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.o A comprehensive retrospective evaluation of the nature of the testing data integrity deficiencies. We recommend that a qualified third-party with specific expertise in the area(s) where potential breaches were identified should evaluate all data integrity lapses.

A current risk assessment of the potential effects of the observed failures on the quality of the drugs you test. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.

A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drug testing results, such as notifying your customers, conducting additional testing, recommending additional studies to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct comprehensive annual audits, for at least two years, to assist in evaluating corrective action and preventive action (CAPA) effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by an independent quality assurance function, along with expertise from outside entities whenever needed).o A status report for any of the above activities already underway or completed.

A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products. Also describe how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.

A list of all method validations performed by your firm since 2022. Provide a third-party assessment of these method validations to determine whether additional development or validation studies are needed. For any method validations requiring revision, provide all correspondence sent to your clients informing them of the need for revisions.

2. 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).

Laboratory Deviations

You failed to adequately investigate laboratory deviations. An unofficial audit form was used to document laboratory deficiencies found on July 7, 2025, including a discrepancy in which microbiological sample plates could not be located in an incubator despite a logbook entry indicating the plates had been placed there (b)(4) earlier. The audit observations were made approximately six weeks before the inspection, but no CAPAs were listed on the form, and the findings were not included in the QU’s deviation and CAPA tracking program.

In your September 15, 2025 response, you stated that the audits were conducted as (b)(4) operational checks to strengthen quality oversight, and you acknowledge the absence of a formal standard operating procedure (SOP) for such practices. You provided an updated SOP that proceduralizes routine process audits and committed to completing CAPAs for the observed items.

Your response is inadequate. The updated SOP allows for routine identification and correction of deficiencies outside of the Quality Management System (QMS) without providing guidelines on when personnel must use the QMS framework for identifying and correcting deficiencies. Without QMS tracking and trending of deficiencies and corrections, the QU cannot ensure adequate CAPAs are implemented, potentially allowing operational deficiencies to persist and compromising testing control.

Unexplained Out of Specification (OOS) Results

You failed to adequately investigate OOS results. On August 31, 2023, you tested (b)(4) for Total Aerobic Microbial Count (TAMC), and on September 11, 2023, reported the results as “Too Numerous to Count (TNTC).” On September 30, 2023 and November 3, 2023, you issued revised test reports for the same sample and test date, listing the TAMC result as passing, with a result of <(b)(4) colony forming units per gram (cfu/g). You had no investigation or supporting documentation available to justify the change from the original TNTC result to the revised <(b)(4) cfu/g result.

On September 15, 2025, you responded that the sample was not for the U.S. market. You also commit to investigating and to revising procedures for re-issuing test reports. In your response of October 15, 2025, you state that your customer directed your firm not to investigate OOS results because the testing was “for informational purposes only.”

Your response is inadequate. A quality agreement with your client does not supersede your CGMP responsibilities. You are responsible for investigating all OOS results to determine whether laboratory errors or other deviations have occurred. These investigations provide assurance that test methods, equipment, materials, and analysts are performing as expected and that all testing, including samples for U.S. drug applications, is reliable. Additionally, your response fails to address that you re-issued test reports with unexplained passing results, and does not include a commitment to audit all test result reports for similar errors or establish interim controls to prevent unauthorized data changes in result reports.

FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any OOS results or significant problems encountered during the testing of these drugs.

For additional information, refer to FDA Guidance for Industry Contract Manufacturing Arrangements for Drugs: Quality Agreements (https://www.fda.gov/media/86193/download).

In response to this letter, provide:

A retrospective, independent review of all invalidated OOS (including in-process, release/stability testing, and “for informational purposes only” samples) results since 2022 and a report summarizing the findings of the analysis, including the following for each OOS:o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root causes are identified for remediation.o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation and any manufacturing operation improvements.

A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include but not be limited to addressing the following:o QU oversight of laboratory investigationso Identification of adverse laboratory control trendso Resolution of causes of laboratory variationo Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequately scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediations

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.

Your laboratory control data was not recorded contemporaneously. Five blank preventative maintenance documents were discovered during the inspection that had been pre-signed and dated to January 9, 2025, in the “Performed by” section. Additionally, your lab manager was observed on August 14, 2025 signing and backdating spectrometry analysis reconciliation records to March 6, 2025. The non-contemporaneous recording of CGMP information is a repeat observation that has been cited in multiple FDA inspections.

In your response, you state that you suspended the supervisor observed backdating documents, commit to performing a third-party review of the extent of the backdating practices, and commit to re-training staff on procedures.

Your response is inadequate. Your response does not include an assessment or commitment to determine the extent of documentation deficiencies throughout your firm and their impact on the integrity of data you provide to drug manufacturers. You also do not propose any global actions to address the data integrity culture at your firm, identify the root cause of continued documentation and data integrity deficiencies, implement adequate controls, or create an environment that prioritizes the handling of data with integrity.

Your customers rely on the integrity of your laboratory data to make decisions regarding drug quality. It is important to maintain strict control ensuring that all laboratory data is retained and that any additions or modifications of information are authorized and appropriately documented.

In response to this letter, provide a complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operations.

Your firm limited access to records requested during the inspection. At the initiation of the inspection, our investigator observed your firm attempting to remove two large garbage bags later determined to contain analytical documents. Other documents that had been removed from the quality control laboratory were requested but were not provided to our investigator.

Additionally, eight process audit forms were discovered in a stack of papers in the Microbiology Laboratory Manager’s office. Your firm had previously denied using the audit forms and then later stated these forms were last used 12 months prior to the inspection. The Microbiology Laboratory Manager stated that senior management instructed him not to share any details about audits with the FDA investigator. No other audit forms were provided by your firm.

When an owner, operator, or agent delays, denies, limits, or refuses an inspection, the drugs manufactured, processed, packed, or held in the facility may be deemed adulterated under section 501(j) of the FD&C Act. See FDA’s guidance document Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection at https://www.fda.gov/media/86328/download.

Your firm’s quality systems are inadequate. See FDA’s guidance document ICH Q10 Pharmaceutical Quality System and Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR parts 210 and 211at https://www.fda.gov/media/71553/download and https://www.fda.gov/media/71023/download, respectively.

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist in connection with the products you test. 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 contract testing laboratory 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 by your clients and tested at Tentamus India Private Limited, Hyderabad, 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 3010960741 and ATTN: Christina Capacci-Daniel.