- Delivery Method:
- Via Email
Recipient NameMr. Nimish Chudgar
Recipient TitleChief Executive Officer & Managing Director
- Intas Pharmaceuticals Limited
Plot No. 255, Magnet Corporate Park, Near Sola Bridge, S.G. Highway
Thaltej, Ahmedabad 382213
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
Warning Letter 320-23-20
July 28, 2023
Dear Mr. Chudgar:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Intas Pharmaceuticals Limited, FEI 3004011473, at Plot No. 5 To 14, Pharmez, Near Village Matoda, Sarkhej-Bavla National Highway No. 8-A, Taluka, Sanand, India, from November 22 to December 02, 2022.
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 December 27, 2022 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’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).
You failed to ensure reliability of data relating to the quality of medicines produced at your facility. Our inspection revealed serious deviations, including but not limited to, inadequate oversight of original CGMP documents, deficient controls over computerized systems, insufficient laboratory investigations, and aborted chromatographic sequences.
Senior facility managers failed to exercise their authority and responsibility to ensure reliable data, leading to severe data integrity deficiencies in your production and laboratory departments. These findings also indicate that your quality assurance function is not exercising its responsibilities, including but not limited to, oversight and control over the adequacy and reliability of CGMP data used throughout your operation.
A. You failed to assure integrity of analytical testing data. Some examples include:
1. Our investigators observed plastic bags filled with torn and discarded original CGMP documents in your quality control (QC) scrap area under a stairwell, in your general parenteral scrap room, and on a truck outside your facility. Among these CGMP documents were engineering checklists associated with the Environmental Monitoring System (EMS), torn Karl Fischer (KF) analytical test reports, auto titration curves, and analytical balance weight slips for finished drug products.
2. An analyst destroyed CGMP records by pouring acetic acid in a trash bin containing analytical balance slips for testing the standardization of (b)(4). A QC employee stated he observed the same analyst destroy KF titration curves and balance printouts. The employee reported the incident to QC laboratory management on November 22, 2022. An investigation into the destruction of the torn CGMP documents and the impact to your drug product quality was not initiated until November 28, 2022.
3. An analyst weighed out the same samples of amitriptyline hydrochloride tablets USP 100 mg batches multiple times for (b)(4) by (b)(4) test. The analyst stated to our investigator that he did not report all the test results, further stating that in some instances balance printouts were discarded in the trash. In addition, the time stamp on each of the analytical balance and (b)(4) printouts did not match your Laboratory Information Management System (LIMS) records.
In your response, you commit to working with a qualified consultant to perform an overall baseline assessment of data integrity and governance controls, and to establish a remediation plan.
Your response is inadequate in that it did not fully evaluate the scope of this deficiency and the impact to product quality. You did not adequately address the major failure of laboratory, operations, and quality assurance management to conduct proper oversight over documentation and prevent data integrity lapses.
B. Your department failed to exercise appropriate controls over computerized systems. For example:
1. Your electronic batch records allowed changes to be made to manual entries prior to saving. Our inspector observed a production employee manually alter the reported time that an operation was performed. QA did not review audit trails as part of their batch record review to identify discrepancies and compare the reported date and time against that which was originally logged.
2. Analysts manually reprocessed chromatograms by adding integration events that were not approved by QC management. In addition, you lacked appropriate procedures describing when the analyst can manually input integration events, how these events should be used, or how they should be reviewed.
3. Destroyed KF raw data paper printouts associated with drug products were discovered by our inspection team in a trash bag. The KF instrument used for water content testing and assay testing is capable of storing electronic data; however, this capacity was not utilized, and you did not save this data electronically.
4. Your 2018 Process Equipment Assessment Report identified numerous gaps and deficiencies for electronic manufacturing equipment needing upgrades in access controls, audit trails, saving electronic data and preventing clock alterations. You had not documented closures of these corrective action and preventive action (CAPA) measures to support data integrity in your computerized systems. Your QA department had not performed a similar assessment in your QC laboratories.
In your response, you acknowledge the inspection findings and you reference your standard operating procedure titled, “Data Integrity,” which stipulates the individuals permitted to make changes in an electronic record and requires audit trails to capture those actions. You also commit to obtaining expertise from a qualified consultant to systematically address the deviations, as part of the baseline assessment.
Your response is inadequate. Although you established procedures, you did not explain the critical failure of laboratory and operations management in not providing adequate oversight of data integrity of computer systems. You also did not address the failure of the QA department to fully exercise its authority and responsibilities to ensure integrity of all data related to manufacturing and quality.
C. You failed to have adequate oversight of laboratory investigations and to implement a systemic CAPA to address the high number of aborted chromatographic sequences. For example:
1. You invalidated multiple out-of-specification (OOS) results for (b)(4) USP without adequate scientific justification. You then prepared new samples and reported passing results. You concluded the OOS results may be due to (b)(4) contamination during initial sample preparation. However, the laboratory investigation, which was approved by QA, did not discuss why other samples in the same analysis of lots, from the same material, prepared by the same analyst, under the same test conditions, were not affected by such contamination.
2. You aborted hundreds of chromatographic sequences in your QC laboratories between January 2020 to November 2022. Each of the incidents were investigated by the quality control laboratory; however, you lacked adequate trending and CAPA systems to evaluate and identify recurring issues that should be targeted for laboratory improvements.
In your response, you acknowledge the need to enhance your processes and practices for investigating laboratory deviations, applying CAPAs, and checking their effectiveness. In addition, you acknowledge the current trending procedures lack systematic tools for conducting evaluations and implementing effective corrective actions.
Your response is inadequate. Your response did not adequately address how you will implement systems to identify and address adverse laboratory incident trends, or provide an overall management strategy for improving all phases of your laboratory investigations.
In response to this letter, provide:
- A comprehensive assessment and remediation plan to ensure your QA department 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 QA 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 QA disposition decision.
o Oversight and approval of investigations and discharging of all other QA duties to ensure identity, strength, quality, and purity of all products.
o 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 retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for U.S. products irrespective of whether the batch was ultimately distributed in the United States for the last three years from the initial date of inspection 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 cause 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, independent assessment and CAPA plan for computer system security and integrity. Include a report that identifies design and control vulnerabilities, and appropriate remediations for each of your laboratory and manufacturing computer systems. This should include but not be limited to:
o A list of all hardware that includes all equipment, both standalone and network, in your laboratory and manufacturing.
o Identification of vulnerabilities in hardware and software, encompassing both networked and non-networked systems (e.g., PLC).
o A list of all software configurations (both equipment software and LIMS) and versions, details of all user privileges, and oversight responsibilities for your computerized systems. Regarding user privileges, specify user roles and associated user privileges (including the specific permissions allowed for anyone who has administrative rights) for all staff who have access to the laboratory and manufacturing computer systems, and their organizational affiliation and title. Also describe how you will ensure staff are not given administrative rights, or other permissions that compromise data retention or reliability.
o System security provisions, including but not limited to whether unique usernames/passwords are always used, and their confidentiality safeguarded.
o Detailed procedures for robust use and review of audit trail data, and current status of audit trail implementation for each of your systems.
o Interim control measures and procedural changes for the control, review, and full retention of laboratory data.
o In addition to interim data retention measures, also provide more comprehensive and sustainable CAPA for retention of all CGMP data. This includes provisions that address not only the need to retain batch-related data for appropriate periods, but also the long-term retention of all source data from development studies that support design, qualification, validation, and application.
o Technological improvements to increase the integration of data generated through electronic systems from standalone equipment (e.g., balances, pH meters, water content testing) into the LIMS network.
o A detailed summary of your procedural updates and associated training, including but not limited to system security control to prevent unauthorized access, and ensure appropriate user role assignments, secondary review of all analyses, and other system controls.
o Your remediated program for ensuring strict ongoing control over electronic and paper-based data to ensure that all additions, deletions, or modifications of information in your records are authorized, and all data is retained. Provide your full CAPA plan and any improvements made to date.
o Provisions for oversight from QA managers, executives, and internal auditors with appropriate IT expertise (e.g., understanding of infrastructure, configuration, network requirements, strict segregation of administrative rights).
2. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).
A. Your laboratory records lacked complete and accurate data to support the analysis performed. Colony forming units (CFU) were not counted accurately in the laboratory's environmental monitoring (EM) data. Our investigators observed colony counts shortly after being read by your analyst for environmental and personnel monitoring that did not match your official records.
Your analyst undercounted carboplatin injection batch EM data by recording two merged colonies as one CFU, despite your procedure stating, “If merged colonies are observed, count it as a separate colony.” Your laboratory identification instrument subsequently identified the joined colonies as two different species.
Notably, you firm indicated no EM results were outside of action limits for Grade A (ISO 5) sample locations from January 2020 until our inspection in November 2022.
B. Laboratory raw data was missing and could not be provided during the inspection. For example, analysts did not consistently include (b)(4) printout raw data in laboratory records. Paper printouts for the (b)(4) determinations and pH printouts could not be reconciled for (b)(4) injection, (b)(4) mg, process validation batch (b)(4).
Because the (b)(4) instrument lacked audit trail capabilities, unreported raw data could not be detected during the QA review process.
Failing to maintain complete records of the data and testing conditions associated with all tests significantly compromises the reliability of data and your QA’s ability to perform its obligation to assure quality through conformance with CGMP.
In your response, you acknowledge EM samples are not counted accurately and that “laboratory practice was to count colonies that merge together with similar morphology, as one colony.” You opened EM investigations for action and alert samples and commit to working with an independent third-party consultant. We also acknowledge you provided modular training for microbiologists and revised standard operating procedures (SOPs).
You also state you investigated the missing (b)(4) instrument print-outs but were unable to definitively determine the root cause of the missing laboratory data. You commit to improvements to the SOPs related to reconciliation of reported results with raw data.
Your response is inadequate. You did not provide the opened investigations or updates to the investigations regarding the EM data or missing laboratory data. You did not commit to a retrospective review and risk assessment of personnel and environmental monitoring data. You did not commit to investigate the impact of missing laboratory data on the process validation batches.
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 contemporaneous, attributable, legible, complete, original, and accurate (ALCOA) records throughout your operation.
- 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.
3. Your firm failed to establish and follow required laboratory control mechanisms (21 CFR 211.160(a)).
Your firm failed to have appropriate procedures for the integration of chromatographic peaks and for the review of chromatographic data.
Our inspection team identified examples of your analysts entering manual integration events that yielded passing results without adequate procedural controls or justification.
In addition, your chromatographic data integration procedure is inadequate because it does not identify when it is appropriate for an analyst to input manual integration events. Your procedure lacked a requirement for supervisory approval and other controls such as data review and justification to consistently document when and why an analyst manually performs integration events.
In your response, you acknowledge the observation and states you misunderstood the regulatory expectation of controls for manual integration. You commit to software upgrades which will maintain all processing parameters and methods. And you commit to working with a qualified third-party consultant to perform an overall baseline audit of the QC laboratories.
Your response is inadequate. You did not commit to performing a retrospective review of all chromatographic data associated with manual integration. We acknowledge your commitment to work with a third-party to audit your QC laboratories; however, you did not provide details such as the scope of this audit or ongoing third-party laboratory activities. You also did not adequately address oversight of the QC laboratory by your QA department and any additional controls to be added to improve consistency of chromatographic practices.
In response to this letter, provide:
- A comprehensive independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Include an assessment of all test methods and procedures used by your firm to ensure they have appropriate instructions, method suitability criteria, and have been appropriately validated to determine whether they are fit for purpose. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
- A comprehensive review and remediation plan for your out-of-specification (OOS) result investigation systems. The corrective action and preventive action (CAPA) should include, but not be limited to, addressing the following:
o Quality unit oversight of laboratory investigations
o Identification of adverse laboratory control trends
o Resolution of causes of laboratory variation
o Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified
o Adequate scoping of each investigation and its CAPA
- Revised OOS investigation procedures with these and other remediations
4. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
Your firm failed to adequately validate the manufacturing process for (b)(4) injection (b)(4) mg. Specifically, your process validation lacked an evaluation of inter-batch and intra-batch variability observed for (b)(4) impurities and (b)(4).
A fourth process validation batch for (b)(4) injection (b)(4) mg was initiated to evaluate related substances from different positions within the (b)(4) due to the incomplete impurity testing. This fourth process validation batch yielded a high OOS result for the (b)(4) impurity. This OOS and failure of the fourth process validation batch was not referenced or discussed in the validation summary report or addendum. A fifth process validation batch was manufactured and included in the addendum report. You subsequently rejected a commercial batch for the U.S. market, (b)(4), due to a high OOS result for the (b)(4) impurity.
In your response you acknowledge the validation program does not evaluate inter-batch and intra-batch variability. You commit to revising your validation program to establish a process to analyze test data within and across batches and to consistently assess the variability of the production process. In addition, you state you will review equipment qualification to evaluate capabilities of the (b)(4).
Your response is inadequate. Your response did not address the omission of the failed fourth process validation batch for the (b)(4) impurity in the approved QA validation report and addendum. Furthermore, your CAPA did not include evaluation of other drug product process validation studies that may be similarly deficient to ensure processes and equipment have adequate data to support their capabilities.
In response to this letter, provide:
- Provide a comprehensive, independent assessment of your validation program for ensuring an ongoing state of control throughout the product lifecycle, including the following elements:
o A description of the overall program (e.g., lifecycle process validation phases; equipment and facility qualification).
o A detailed description of how you ensure a rigorous process performance qualification studies. Include specific quantitative approaches with intensified sampling plans to fully assess all significant process steps, and explain how these extensive levels of sampling characterize the intra-batch uniformity at these steps to provide a high level of assurance that supports a decision on readiness for marketing
o Vigilant ongoing monitoring of process performance and product quality throughout the lifecycle, with emphasis on:
Mechanisms to ensure ongoing attention to both intra-batch and inter-batch variation
Appropriate sampling methods and frequency throughout processing to ensure detection of process control lapses
Scrutiny of raw material variability from suppliers
Quality signals from both internal data and customers
How your quality system integrates this ongoing knowledge of signals from process performance and product quality monitoring to identify areas of variation that need improvement.
o Based on this assessment, provide a CAPA to address any deficiencies in your process validation program
5. Your firm failed to establish the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
Your QA department did not ensure raw materials used in the manufacture of drug products were appropriately tested. Your firm failed to perform method validation (or verification, as appropriate) of test methods to ensure that they were suitable for their intended use. You provided a list of multiple in-house methods and compendial methods which have not been validated or verified, including for raw materials such as (b)(4).
Method validation and verification is necessary to support reliable determination of identity, strength, quality, purity, and potency of drugs. Without evaluating the validity of methods, you lack the basic assurance that your laboratory data accurately reflects drug product quality.
In your response, you acknowledge all materials used for manufacturing need to be tested using methods that have been validated or verified. You commit to reviewing the procedures governing method validation and method verification as well as technical transfer to ensure that the procedures comply with FDA regulations.
In response to this letter, provide:
- A detailed, independent assessment of all test methods to evaluate if they include sufficiently specific instructions to ensure repeatability, are supported by adequate validation (or verification, for United States Pharmacopeia (USP) compendial methods) studies, and are appropriate for their intended use. The assessment should also determine whether test methods used in the stability program are stability-indicating. The scope of the assessment should encompass any tests conducted by your firm or its contract laboratories.
Other Inspectional Findings
We acknowledge your plan to conduct new smoke studies under dynamic conditions to improve your evaluation of the effect of interventions and interactions (i.e., mobile cart transfers, other material transfers) on airflow within the (b)(4) Restricted Access Barrier System ((b)(4)RABS). In your response to this letter, provide updated static and dynamic smoke studies, or a commitment to provide these studies upon their completion.
Data Integrity Remediation
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers
We acknowledge that you are using a consultant to audit your operation and assist in meeting FDA requirements. In response to this letter, provide:
A. A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:
- 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.
- 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.
- 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.
- A comprehensive retrospective evaluation of the nature of the testing and manufacturing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.
B. A current risk assessment of the potential effects of the observed failures on the quality of your drugs. 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.
C. A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include these elements:
- 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.
- 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.
- Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
- 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.
- A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.
- Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to maintain anonymity of employees who report data integrity concerns and with authority to ensure any potential breach is investigated.
- A status report for any of the above activities already underway or completed.
Repeat Observations at Facility
In previous inspections, including the inspection of May 20-28, 2019 FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.
Ineffective Quality System
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 production and laboratory operations oversight, we found your quality unit 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.
Test Results Out-of-Specification
For more information about handling failing, out-of-specification, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigating-out-specification-oos-test-results-pharmaceutical-production-level-2-revision. A possible laboratory error is insufficient to close an investigation at Phase 1. Whenever an investigation lacks conclusive evidence of laboratory error, a thorough investigation of potential manufacturing causes must be performed.
Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure 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. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility in connection with your products. 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 firstname.lastname@example.org, 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.
FDA placed your firm on Import Alert 66-40 on June 1, 2023.
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 continuing to refuse admission of articles manufactured at Intas Pharmaceutical Limited at Plot No. 5 To 14, Pharmez, Near Village Matoda, Sarkhej-Bavla National Highway No. 8-A, Taluka, Sanand, 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).
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 days1. 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 3004011473 and ATTN: Erika V. Butler.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
1 Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.