Intas Pharmaceuticals Limited - 652067 - 07/28/2023 | FDA https://www.fda.gov/inspections-compliance-enforcement-and-criminal...

WARNING LETTER

Intas Pharmaceuticals Limited

MARCS-CMS 652067 — JULY 28, 2023

Delivery Method:
Via Email
Product:
Drugs

Recipient:
Mr. Nimish Chudgar
Chief Executive O�cer & Managing Director
Intas Pharmaceuticals Limited
Plot No. 255, Magnet Corporate Park, Near Sola Bridge, S.G. Highway
Thaltej, Ahmedabad 382213 Gujarat
India

Issuing O�ce:
Center for Drug Evaluation and Research | CDER
United States

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).

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your

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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
[email protected], 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 [email protected]. Identify your response with FEI
3004011473 and ATTN: Erika V. Butler.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research

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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.

 More Warning Letters (/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters)

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Intas Pharmaceuticals Limited - 652067 - 07/28/2023 | FDA https://www.fda.gov/inspections-compliance-enforcement-and-criminal...

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