Delivery Method: VIA EMAIL WITH READ RECEIPT Reference #: 320-25-103 Product: Drugs Recipient:
Recipient Name
Mr. Heath Ashenfelter
Recipient Title
President and CEO
Wisconsin Pharmacal Company, LLC
1 Pharmacal Way
Jackson, WI 53037
United States
Issuing Office: Center for Drug Evaluation and Research (CDER)
United States
Warning Letter 320-25-103
August 22, 2025
Dear Mr. Ashenfelter:
The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Wisconsin Pharmacal Company, LLC, FEI 2124143, at N168 W 22223 Main St., Jackson, WI, from March 3 to 7, 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 March 27, 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’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 quality unit (QU) did not provide adequate oversight for the manufacture and release of your over-the-counter (OTC) drug products. For example, you filled batch (b)(4) of your (b)(4) Spray from vessels (b)(4). Your QU rejected the drug product units filled from vessel (b)(4) because they failed assay test release specification for (b)(4). You attributed insufficient (b)(4) of the corresponding batch in vessel (b)(4) as the root cause. However, you released drug product filled from vessels (b)(4).
In addition, your QU failed to exercise its responsibility by not withholding from distribution all rejected units filled from vessel (b)(4) and instead allowing the distribution of approximately half of the rejected drug product. Your practice of rejecting a partial drug product batch is an indication that your firm does not have well-controlled manufacturing and release procedures.
In your response, you acknowledge that the rejected drug product was not adequately identified and contained due to improper scanning procedure. You took a corrective action that included revising your procedure for non-conforming and rejected materials and retraining your staff.
Your response is inadequate because you do not provide details on how your corrections and corrective actions will prevent recurrences of distributing rejected drug products to customers. You fail to address the fundamental deficiencies in your QU that led to these failures. You do not provide a comprehensive corrective action and preventive action (CAPA) plan with a systematic approach to correct these oversight deficiencies.
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/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.
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:
• A determination of whether all procedures used by your firm are robust and appropriate.
• A retrospective review of testing results for all released drug products. If failures are identified, take rapid corrective actions, such as notifying customers and drug product recalls.
• Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
• A complete and final review of each batch and its related information before the QU disposition decision.
• Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all drug products.
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).
You failed to adequately investigate multiple microbial excursions reported for objectionable microorganisms found during testing of your OTC drug products. For example, objectionable microorganism Staphylococcus aureus (S. aureus) was identified during drug product batch testing, including but not limited to:
• On November 11, 2024, objectionable microorganism S. aureus was found in your (b)(4) Cream, batch (b)(4). You released the referenced batch for commercial distribution based on a passing retest result obtained without conducting a thorough investigation into the root cause of the contamination.
Without a comprehensive investigation into your manufacturing process and supporting data, you claimed the root cause of the contamination of the (b)(4) Cream batch was due to microbial testing and that S. aureus is commonly found on human skin. You concluded there was no evidence to suggest batch contamination because no growth was detected during repeat testing of the original tube and retain samples.
• On August 19, 2024, objectionable microorganism S. aureus was found in your (b)(4), batch (b)(4). After retesting, you rejected drug products filled from the (b)(4) impacted vessels. You did not conduct a thorough investigation to determine the root cause of the contamination, and you released drug product units filled from the remaining (b)(4) other vessels based on passing retest results.
Your determination regarding the scope of the microbial contamination is flawed. Microbial contamination may not be uniformly distributed, and passing sample results obtained from units filled from one vessel or container may not be indicative of results from other portions of a batch. As a manufacturer, you have a responsibility to fully investigate microbial contamination results that may impact drug product quality.
In your response, you acknowledge that you failed to perform a holistic investigation into the root cause of the microbial contamination by including a review of data from environmental monitoring, cleaning, and sanitization as part of the investigation. You also acknowledge that you incorrectly relied on the retest data without adequately investigating the contamination source prior to retesting. You commit to immediately begin additional sanitizations and cleaning until the root cause of contamination is identified. You also commit to creating and revising procedures for routine equipment surface monitoring and providing a detailed investigation process for microbial contamination.
Your response is inadequate because you fail to provide a comprehensive assessment of microbial contamination in your OTC drug products, including but not limited to, a review of elements of your operation that may introduce bioburden or permit microbial proliferation. Your response lacks a comprehensive drug product impact assessment.
In response to this letter, provide:
• A comprehensive independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification 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 assurance oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
o Include your updated investigation procedures and a clear description of how investigations are initiated, documented, and completed.
• A comprehensive independent assessment of the design and control of your firm’s manufacturing operations, with a detailed and thorough review of all microbiological hazards. Also address the hazards posed by distributing drug products that are objectionably contaminated. Specify actions you will take in response to the risk assessment, such as customer notifications and drug product recalls.
• A summary of all results obtained from testing retain samples from each batch of the (b)(4) drug product.
• A list of all investigations into all batches with potential objectionable microbial contamination, including but not limited to, any out-of-specification (OOS) result, whether or not later invalidated. Include a copy of the complete investigations that detail your findings regarding the root causes of the contamination and any CAPA that were identified.
3. 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 firm lacked sufficient controls over your liquid chromatography (LC) and gas chromatography (GC) instrument used to test drug products prior to release. Specifically, your firm did not appropriately control administrative privileges for file modification and deletion using your Agilent OpenLab software data system.
During the review of analytical system audit trails for final release testing of finished OTC drug products, our inspection found that your firm does not review audit trails and raw analytical data captured by these analytical instruments. You do not have written procedures to review electronic data or integration to ensure data reliability for batch release.
Your quality system does not adequately ensure the adequacy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. Without complete and accurate records, you cannot assure appropriate decisions regarding batch release, drug product stability, and other matters that are fundamental to ongoing assurance of quality.
Your response acknowledges that your firm failed to appropriately set up the instrumentation software used for data collection and analysis of OTC drug products. You also acknowledge that your firm failed to review audit trails and establish an SOP requiring review of computer-generated data during batch release testing. You commit to taking corrective actions, including updating user access and permissions for all lab instruments and creating a new SOP requiring review of raw data and audit trails prior to batch release.
Your response is inadequate because it lacks an independent review including, but not limited to, an assessment of drug product impact and whether a retrospective review is warranted based on the drug product impact assessment. Your response also did not provide adequate details of management oversight to ensure effectiveness of the corrective actions implemented.
In response to this letter, provide:
• A comprehensive, independent assessment of computer system performance and security. Provide a report that identifies vulnerabilities in the design and controls, and a thorough corrective action and preventive action (CAPA) plan for each of your laboratory computer systems, which addresses the following elements:
o A list of all hardware (both standalone and networked) and software used by your laboratory.
o Identify and evaluate vulnerabilities in performance and security of all of these computer systems, including but not limited to their configurations, administrative rights, password controls, audit trails capabilities and state of implementation for each system, qualification/validation status, deviation history, backup capabilities, network requirements, completeness of data records, suitability of current hardware/software for its intended use(s), change management, and management oversight.
o Detail the associated user privileges for each system.
Specify user roles and associated user privileges for all staff levels who have access to the laboratory computer system, and provide organizational affiliations, responsibilities, and titles. Clearly specify all staff who have administrator privileges.
Fully describe how you will ensure segregation of firm personnel involved with laboratory testing from those with administrator rights. For all staff roles that are permitted to have administrative rights, specify the scope and type of privileges.
o Assess each system to determine if unique usernames and passwords are used.
o Evaluate policies and procedures regarding computers and data governance with special emphasis on audit trails, prohibiting data deletion, and appropriate modifications of results. Specify how your firm prevents data deletion and undocumented/inappropriate modifications of data. Also describe how you ensure original data and information are always preserved. Provide your procedures for audit trail review.
o Provide requirements for data retention and backup for all laboratory systems.
o Describe how you will ensure that all quality control tests are performed by an analyst and receive second-tier review from a separate qualified individual (e.g., lab manager). Provide related procedure(s).
o Summarize your interim controls to assure reliable performance and security while your CAPA plan is being implemented.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend that your firm 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 address this matter promptly and adequately 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 2124143 and ATTN: Joan Johnson.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
