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Warning Letter 320-26-32

December 19, 2025

Dear Mr. Patel:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Unipack LLC, FEI 3008275696, at 111 Coolidge St., South Plainfield, NJ 07080-3801, from June 11 to June 30, 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 July 22, 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).

Your firm failed to conduct adequate investigations into out-of-specification (OOS) results and unknown peaks in chromatograms. For example:

A. Your (b)(4) suppositories batch #(b)(4) three-month long-term (25ºC / 60% relative humidity) stability sample assay result was (b)(4) mg (b)(4) per suppository (acceptable range: (b)(4) mg). Your investigation included multiple retests with results ranging from (b)(4) to (b)(4) mg per suppository. You invalidated the original OOS result with no identified laboratory error and no explanation for the significant differences in assay results. Your investigation also lacked root cause identification before releasing the product for distribution and you failed to implement corrective action. We note the stability sample at the intermediate condition (30ºC / 65% relative humidity) for the same batch also failed to meet the assay specification.

B. You obtained an OOS content uniformity test result of (b)(4)% (b)(4) for your (b)(4) suppository batch #(b)(4) (acceptable range: (b)(4)%). Your investigation included reanalysis of the original sample, which resulted in an OOS result of (b)(4)%. However, your investigation lacked scientific justification to invalidate the OOS result and ultimately release the batch.

C. Unknown peaks were not integrated or properly investigated in HPLC chromatograms of multiple drug products, including, but not limited to, (b)(4) suppository batch #(b)(4). You also inhibited peak retention time between (b)(4) and (b)(4) for the same drug product. Inhibiting peak integration and restricting integration parameters must be scientifically justified and documented in the validated method to prevent data manipulation.

Inadequate investigations can result in unsupported root causes, ineffective corrective actions, and recurring problems that compromise your ability to manufacture safe and effective drug products.

In your response, you attribute the (b)(4) suppositories batch #(b)(4) OOS stability result to improper processing of the injection. Your response regarding the OOS results for (b)(4) suppositories batch #(b)(4) reiterates the original investigation’s conclusion and fails to provide additional evidence or analysis beyond what was reviewed during the inspection. Additionally, you state you have discontinued HPLC testing throughout your facility. You also explain the unknown peaks in (b)(4) suppository batch #(b)(4) are attributable to excipients but fail to address your practice of inhibiting peak integration and restricting integration parameters.

Your response is inadequate. You fail to provide additional details of your investigation into OOS results of your (b)(4) suppositories and (b)(4) suppositories, including determination of root causes and CAPAs. Additionally, you do not explain the root cause of your QU’s failure to thoroughly investigate unknown peaks before releasing the product. Furthermore, your commitment to discontinue HPLC testing at your facility does not address how you will ensure future deviations are investigated by following robust procedures.

In response to this letter, provide:

• 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, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
• An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final QU decisions, and is fully supported by executive management.
• A thorough assessment of the adequacy of your test methods used for testing and retesting OOS samples.
• 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 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 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

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)).

Your laboratory records did not include all testing data to support the drug product analyses performed.

Incomplete laboratory records

Our investigator observed entries were not entered contemporaneously in your laboratory notebook. For example, our investigators observed volumetric flasks of (b)(4) suppository finished product release and stability samples in your quality control laboratory with no date of preparation documented. Your analyst stated the samples were prepared on June 9, 2025.

However, the last entry in your laboratory notebook was dated June 4, 2025. Furthermore, the sample weights were recorded on an adhesive note, and no standard weight was recorded. All raw data must be recorded in a controlled document at the time they are observed or measured to ensure data integrity.

Our investigators also noted multiple high-performance liquid chromatography (HPLC) injections were not adequately processed in the chromatographic system. For example, electronic records stored in a folder titled “(b)(4)” indicate that approximately (b)(4) sample injections were performed. However, results were generated only for approximately (b)(4) injections. Your firm lacked evidence to demonstrate your laboratory manager and quality unit (QU) reviewed the raw data for these injections. Furthermore, HPLC audit trails revealed the (b)(4) suppositories batch #(b)(4) three-month stability sample was injected on September 25, 2023, but results were neither processed in your HPLC system nor documented in your laboratory notebook. In addition, the (b)(4) suppositories batch #(b)(4) 24-month stability sample was initially injected on April 29, 2025, with no reported results, then re-injected later that same day, with passing results subsequently reported.

All laboratory records must be complete, accurate and contemporaneously documented to ensure processes are consistently followed and reproducible. Additionally, incomplete laboratory records deprive you of the ability to adequately investigate deviations.

Inadequate electronic records controls

Your firm did not have proper controls in place to prevent the deletion or manipulation of your laboratory's electronic data. For example, your analysts had administrative rights on your chromatographic systems that allowed them to alter and delete data, files, and folders, including your spreadsheet used for assay calculations. In addition, during a review of system audit trails, our investigator observed multiple “deleted system” and “deleted project” errors with no assessment report completed as required by your procedure. Deficiencies in your electronic data security controls were identified and discussed during previous FDA inspections, yet your firm has failed to implement adequate corrective measures. The lack of proper electronic records controls undermines the reliability and integrity of your laboratory data.

Manual Integration

Your analysts conducted manual integration of HPLC assay peaks without scientific justification or procedural controls. For example, our review of chromatograms for (b)(4) suppositories stability batch #(b)(4) revealed the use of inconsistent integration for the main peak of interest for HPLC assay testing. This inconsistent integration of HPLC peaks is not suitable for quantitative analysis.

All data must be complete, accurate, and retained to enable appropriate assessments and decisions by the QU. The lack of control over the integrity of your data raises questions about the authenticity and reliability of your analytical data and the quality of your drug products.

In your response, you state all internal HPLC testing is permanently discontinued, and all chromatographic analysis transitioned to qualified third-party laboratories.

Your response is inadequate. Your elimination of internal HPLC testing does not address your fundamental breaches of data integrity. In addition, you lack a comprehensive assessment to determine the full extent and impacts of your data integrity deficiencies, including a retrospective review of your manual integration practices.

In response to this letter, provide:

• A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine the adequacy of your documentation practices. 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.

3. 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)).

Your firm lacked appropriate testing to ensure finished drug products conform to appropriate standards of identity, strength, quality, and purity. For example, the United States Pharmacopeia (USP) monograph for (b)(4) suppositories includes specific testing for identification and (b)(4) determination, but your finished product release specifications did not include these required tests. Your firm manufactured and distributed approximately (b)(4) batches of (b)(4) suppositories since March 2022 without adhering to USP testing standards. Additionally, your finished product release specifications for (b)(4) suppositories did not include the specific identification testing required in the USP monograph.

You failed to establish that your test methods and specifications are scientifically sound and appropriate or that they are equivalent to or better than the current USP compendial methods.

In your response, you acknowledge comparing your product specifications against USP and CGMP requirements to identify testing gaps for remediation. You then revised your product specifications to meet analytical requirements and shared the updated specifications with your third-party laboratories. You also state you are implementing a “risk-based confirmatory testing plan across relevant product lines.”

Your response is inadequate. You fail to provide an adequate timeline for transferring testing to contract laboratories. Additionally, you propose to continue risk-based retroactive testing in-house despite acknowledged testing deficiencies. Furthermore, you continue manufacturing and releasing products without having fully remediated your laboratory deficiencies.

In response to this letter, provide:

• A comprehensive, independent 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.
• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a batch disposition decision.
  o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

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 strongly recommend you retain an independent third-party qualified consultant with experience identifying and remediating data integrity issues. In response to this letter, provide:

• Copies of any agreement describing the roles and responsibilities of your independent third-party consultant. Include copies of any protocol developed, system-based assessment, and report as part of your remediation effort.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
• 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 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.
  o A comprehensive retrospective evaluation of the nature of the 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.
• 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.
• A management strategy for your firm that includes the details of your global corrective action and preventive action 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 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.
  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 two years, to assist in evaluating corrective action and preventive action (CAPA) effectiveness after you have executed your data integrity 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 data integrity 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.

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

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 3008275696 and ATTN: Matthew Jensen.

Sincerely,
/S/

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