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WARNING LETTER

Seatex, LLC MARCS-CMS 672951 —


Delivery Method:
VIA Electronic Mail
Product:
Drugs

Recipient:
Recipient Name
Jonathan P. O’Dwyer
Recipient Title
President and CEO
Seatex, LLC

445 Texas Highway 36
Rosenberg, TX 77471
United States

Issuing Office:
Division of Pharmaceutical Quality Operations II

United States


Date: April 1, 2024

Case # 672951

WARNING LETTER

Dear Mr. O’Dwyer:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Seatex, LLC, FEI: 3007709579, at 445 Texas Highway 36, Rosenberg, Texas, from October 16, 2023, to October 20, 2023.

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 November 3, 2023, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your
operations into compliance with CGMP.

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

1. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).

Your firm manufactured over-the-counter (OTC) hand sanitizer drug products on equipment also used to manufacture non-pharmaceutical products, including industrial chemicals such as floor cleaner. It is unacceptable as a matter of CGMP to manufacture drugs using the same equipment that you use to manufacture these non-pharmaceutical products due to the risk of cross-contamination. Additionally, you could not provide cleaning validation studies to support your equipment cleaning procedures and post-wash testing.

In response to this letter, provide:

  • For drug product dedicated equipment, a comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment, facility piping, or storage vessels that may have been improperly cleaned, and an assessment whether cross contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices and encompass each piece of manufacturing equipment used to manufacture more than one product.
  • Your corrective action and preventive action (CAPA) plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment and facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment and facility infrastructure, and improved systems for ongoing management review.
  • A CAPA plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning execution for all products and equipment; and all other needed remediations.
  • A summary of updated standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.

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).

Your firm did not adequately investigate out-of-specification (OOS) results. Specifically, your practice to test a new sample if the original result fails, until either a third failing result or a passing result is obtained, is not scientifically justified. Additionally, your firm does not record or retain the OOS test results for review or investigation. You also could not provide a procedure or policy governing retesting following an OOS result.

Failing to maintain complete records of the data associated with all tests significantly compromises the reliability of data and your quality unit’s (QU) ability to perform its obligation to assure quality through conformance with CGMP. 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-guidancedocuments/investigating-out-specification-test-results-pharmaceutical-production.

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 operation.
  • A retrospective, independent review of all invalidated OOS (including in-process and release and stability testing) results for U.S. products 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 and 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 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 Adequately scoping of each investigation and its CAPA.
    o Revised OOS investigation procedures with these and other remediations.

3. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm does not perform identity testing for incoming components, including ethanol and glycerin, to ensure they are suitable for use in your drug products. Further, your incoming material specifications for ethanol did not include testing for impurities such as for methanol, and your specifications for glycerin did not include a limit test per the United States Pharmacopeia (USP) to ensure that the glycerin meets the relevant safety limits for the levels of diethylene glycol (DEG) or ethylene glycol (EG). Additionally, you accepted supplier certificates of analysis, which did not include complete testing, without establishing the reliability of your component suppliers’ test analyses at appropriate intervals. Lastly, you could not provide quality agreements with your ethanol suppliers or records establishing that you had audited your ethanol suppliers for suitability.

The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol at https://www.fda.gov/media/173005/download.

The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol to help you meet the CGMP requirements when manufacturing drugs, including repackaged drugs at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.

Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.

In response to this letter, provide:

  • A description of how you will test each lot for conformity with all appropriate specifications for identity, strength, quality, and purity.
  • A commitment to always conduct at least one specific identity test for each container of each lot of each shipment. In the case of glycerin, propylene glycol, and certain additional high-risk drugs, we note that this includes the performance of parts A, B, and C of the USP monograph.
  • A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
  • A summary of your program for qualifying and overseeing contract facilities that test the drug components you manufacture.

4. 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 firm’s quality system was inadequate. Specifically, your firm was unable to demonstrate that your QU had the responsibility and authority to ensure critical elements of drug product manufacturing operations were adequately controlled.

During the inspection, you could not provide numerous manufacturing records, such as equipment validation records, reverse osmosis water system validation records, or process performance qualification records for your OTC drug products. Furthermore, you failed to have a procedure governing the monitoring of your reverse osmosis water system, including validated test methods.

An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. Your firm’s quality systems are 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 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 and quality issues and to assure a continuing state of control.

  • A remediation plan that better assures ongoing management oversight throughout the manufacturing lifecycle of all drug products. Provide a more data-driven and scientifically sound program that identifies sources of process variability and assures that manufacturing operations meet appropriate parameters and quality standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step and its controls, and vigilant ongoing monitoring of process performance and product quality.

On February 8, 2024, FDA held a teleconference with you. We recommended you voluntarily remove any batches of drug products currently in distribution from the U.S. market.

On February 19, 2024, you issued a voluntary nationwide recall of the following four products: 7-11 Ethanol Green Gel, Antibacterial Foam Soap-Spring Waters, Sanitizer Foam, and 7-11 Ethanol Gel (Dye Free).

Drug Production Ceased

We acknowledge your commitment to cease production of all drugs at this facility. In response to this letter, clarify whether you intend to resume manufacturing any drugs at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to FDA, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.

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.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. 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 address any violations.

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.

Please electronically submit your reply on company letterhead to Mark W. Rivero, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to Mark.Rivero@fda.hhs.gov and Ronda Loyd-Jones, Director, Compliance Branch at Ronda.Loyd-Jones@fda.hhs.gov.

If you have questions regarding the contents of this letter, you may contact Mr. Rivero via phone at (954) 759-7718 or email at Mark.Rivero@fda.hhs.gov.

Sincerely,
/S/

Tamala Bogan
Acting Program Division Director
Office of Pharmaceutical Quality Operations,
Division II

 
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