Warning Letter 320-25-52

March 10, 2025

Dear Mr. Munday:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, International Laboratories Corp, FEI 3006403166, at Bangplee District, 62 Moo 8, Bang Na-Trat Rd, Bang Phli, Samut Prakan 10540, Thailand, from September 16 to 20, 2024.

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 October 11, 2024 response to our Form FDA 483 in detail.

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. 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)).

Your laboratory records lacked complete and reliable original data to support the chromatographic analyses performed on over-the-counter (OTC) drug products and components. For example, our investigators documented multiple examples of fabricated laboratory records. During the inspection, your Laboratory Manager stated that your firm fabricated several laboratory investigations that were not performed. A senior Quality Assurance Manger also confirmed that laboratory investigations were fabricated in preparation for the FDA inspection. Further, you did not maintain the original data from the analytical testing of raw materials and finished products.

In your response, you acknowledge that your laboratory system lacks appropriate procedures and controls to ensure the completeness and integrity of your data and you committed to improvements. Your response is inadequate as it does not adequately evaluate the full scope of data integrity (DI) deficiencies throughout your drug product manufacturing operations.

Reliability of data is fundamentally compromised when there is a failure to record or maintain complete and accurate records of test results, or conditions associated with all tests. Furthermore, the lack of reliable data compromises the quality unit’s (QU) ability to exercise its function of ensuring compliance to applicable standards.

2. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

Your laboratory equipment, used to generate analytical data for finished drug product release and stability testing, lacked restricted access and sufficient controls. Specifically, your firm did not have proper controls in place to prevent the deletion or record manipulation of your laboratory's electronic raw data. For example, our investigator documented numerous examples of deleted electronic raw data files. Additionally, your analysts had administrative rights capable of altering and deleting data, files, and folders on your chromatographic systems, including the date and time of tests.

We also note that you did not ensure retention of complete electronic raw data for all laboratory instrumentation and equipment. For example, our investigators documented several electronic data results that were not available for review.

In your response, you acknowledge the lack of document control and state that you have initiated change controls to reduce DI gaps identified during the inspection. Your response is inadequate because you failed to include a comprehensive review of each piece of equipment and the impact of the significant adverse pattern of data that has been discarded or lost. Your impact assessment commitment is also limited to missing (b)(4) test data and stability.

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 DI practices at https://www.fda.gov/media/119267/download.

We strongly recommend that you retain an independent third-party qualified consultant to assist in your remediation. In response to this letter, provide:

• A comprehensive investigation into the extent of the inaccuracies 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 DI 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 DI lapses. o A comprehensive retrospective evaluation of the nature of the testing/manufacturing/other DI deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all DI lapses.
• 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 DI 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 (CAPA) 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 DI 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 DI 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 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.
  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 extensive annual audits, for at least 2 years, to assist in evaluating CAPA effectiveness after you have executed your DI 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 DI concerns and with the authority to ensure any potential breach is promptly investigated (by 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.

3. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).

Your QU did not provide adequate oversight for the manufacture of your products. For example, you stated that you could not provide records to support the CGMP requirements for the manufacture of drugs, including but not limited to the following:

• Finished product original release testing data
• Original stability testing data
• Sample collection and preparation
• Procedures for quality control data review (e.g., raw material, finished product release, and stability testing)
• Batch production and control record

In your response, you state that controls are being implemented to establish requirements for CGMP activities across operations and laboratory staff. Your response is inadequate. You failed to address the potential impacts on all drug product lots distributed to the United States that remain within expiry and were manufactured without documentation of testing performed.

In a previous warning letter (320-23-34), FDA cited similar CGMP violations. You proposed remediation and committed to conducting a full six-system audit with a qualified CGMP consultant in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

See FDA’s guidance document 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 211 at https://www.fda.gov/media/71023/download.

In your response to this letter, provide:

• 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.
  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.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

FDA placed your firm on Import Alert 66-40 on August 7, 2023, after your response to our 704(a)(4) Request for Records sent to you on March 17, 2023, demonstrated CGMP violations related to controls for DEG/EG in high-risk components used in your drugs.

The inspectional findings detailed above further demonstrate your firm’s noncompliance.

Your firm remains on Import Alert 66-40.

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 International Laboratories Corp, Bang Phli, Samut Prakan 10540, Thailand, 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. 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 3006403166 and ATTN: Zachary Bogorad.

Sincerely,
/S/

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