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Warning Letter 320-26-33

December 23, 2025
 

Dear Mr. Needleman:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Tower Laboratories Ltd., FEI 1823985, at 8060 Whitbeck Road, Montague, from July 8 to 11, 2025.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, 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 August 1, 2025, 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 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).

You manufacture over-the-counter (OTC) drug products, including (b)(4) medications. You failed to thoroughly investigate several out-of-specification (OOS) laboratory results from October 2024 to June 2025 and lacked corrective action and preventive action (CAPA). For example, (b)(4) tablets, lot (b)(4), and (b)(4) tablets, lot (b)(4), failed assay testing at the 9-month stability timepoint. Your retest using additional samples also produced failing results. Your laboratory investigations did not include sufficient details and lacked root causes for the failures. Furthermore, you did not notify your customers about the failing stability results for the distributed lots.

In your response, you state that while the above investigations did not identify root causes, the OOS results are “representative of microscopic packaging defects” noted in a previous investigation and “are not formula stability related.” You acknowledge that you did not take market action for the failing batches, despite noting the possibility that the defects may impact drug product effectiveness.

Your response is inadequate because your investigation lacked sufficient rigor to show how your “packaging defects” led to a failure in product quality. Additionally, you failed to initiate a CAPA at the conclusion of the investigations. This was a repeat observation from FDA's 2021 inspection where you attributed the root cause of assay failures to packaging defects without providing supporting evidence of how these defects impact your analytical methodology and failed to implement appropriate CAPA.

Inadequate investigations can lead to unidentified root causes, ineffective CAPA, and recurring problems that compromise the ability to manufacture safe and effective drug products.

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.

In response to this letter, provide:

• A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for U.S. products currently in the U.S. market and within expiry as of the date of this letter 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 demonstrate 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 review and remediation plan for your OOS result investigation systems. The 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
  o Revised OOS investigation procedures with these and other remediations
• 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.

2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

You failed to demonstrate that your sample preparation methods are suitable for testing drugs or to account for how these methods could affect test results. For example, you use (b)(4) to prepare samples of your (b)(4) tablets and (b)(4) tablets for high-performance liquid chromatography analysis. However, (b)(4), which can lead to inaccurate results showing OOS levels for (b)(4) content.

In your response, you acknowledge that you did not fully meet the test method validation requirements, and that you will review and re-validate (b)(4) of your test methods assaying for (b)(4) in (b)(4) of your formulations. You commit to updating your analytical method validation master plan to incorporate all current test method validation requirements. You also commit to reviewing all other test methods used to assay your other OTC drug products.

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 commit to a retrospective review and risk assessment for all test results generated using these methods. Additionally, you have not established interim controls to use during the review and validation of your test methods.

In response to this letter, provide:

• An evaluation of the adequacy of your analytical sample preparation methods by verifying suitability through documented protocol, analyzing recurring errors throughout the methods’ history, and implementing CAPA measures to address test method deficiencies.
• A comprehensive assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

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.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 1823985 and ATTN: Renee A. Marcsisin, Ph.D.

Sincerely,

/S/

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