FDA向澳大利亚VeganicSKN Limited发出警告信320-26-44，涉OOS调查等CGMP违规

Delivery Method:

Via Electronic Mail - Return Receipt Requested

Reference #:

320-26-44

Product:

Drugs

Recipient:

Recipient Name

Mr. Joseph Mizikovsky

Recipient Title

Chief Executive Officer

VeganicSKN Limited

243 Milton Road
Brisbane QLD 4064
Australia

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-44

February 9, 2026

Dear Mr. Mizikovsky:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, VeganicSKN Limited, FEI 3024609429, at 81 Shettleston Street, Unit III, Rocklea, Queensland, Australia, from July 15 to 21, 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 11, 2025, response to our Form FDA-483 in detail, and we acknowledge receipt of your subsequent correspondence.

During our inspection, our investigator 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 an adequate and timely out-of- specification (OOS) investigation for your (b)(4) drug product. Your contract testing laboratory reported an OOS result for (b)(4) on August 28, 2024, but you did not initiate the Phase II investigation until December 4, 2024. Despite the ongoing investigation, your quality unit (QU) released the batch on (b)(4), and subsequently shipped the batch for the U.S. market on (b)(4), after your firm retested the sample and obtained passing results. A root cause was not determined for the OOS result, and the investigation was closed on July 11, 2025.

In your response, you state that you opened a corrective action and preventive action (CAPA) plan that includes updating your procedure for releasing drug products, and you conducted a risk assessment to determine the final disposition of this lot, which is still within expiry and any subsequent market action.

Your response is inadequate because it fails to provide a justification for not completing your OOS investigation for nearly 11 months. Additionally, while you state that the OOS drug product was shipped because of a breakdown in your drug product-release procedure, you did not determine the root cause for the actual OOS result, nor did you conduct a comprehensive assessment of your quality system to ensure that all OOS investigations have been adequately investigated.

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

For more information about handling failing, OOS, 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/media/71001/download.

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 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 Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified
  o Resolution of causes of laboratory variationsInitiation 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 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 did not adequately test your incoming component, (b)(4), for identity prior to use in manufacturing. (b)(4) is a component that is at high risk for (b)(4) contamination. Your firm also accepted the (b)(4) raw material based on the supplier’s certificate of analysis (COA), without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals. Additionally, the (b)(4) lot you utilized for drug product production had expired.

In your response, you state that you opened a CAPA, performed a risk assessment, and sent all remaining drums of (b)(4) out for testing. In addition, you state that your firm is evaluating the (b)(4) of your (b)(4) products to a lower-risk excipient, to eliminate supply chain risk in all future productions.

Your response is inadequate. Your risk assessment is theoretical. You conclude that the risk is low based on (b)(4) and (b)(4) application. You did not correlate the assessment to the actual test results for all affected lots. Additionally, your firm acknowledges that identity testing based on supplier COA plus FTIR was inadequate for high-risk materials like (b)(4), yet you still reference past acceptance decisions as part of your justification. Acknowledging the gap does not mitigate the fact that your product was released under a flawed system, without appropriate controls in place at the time. Further, while you describe retrospective testing of remaining drums, there is no clear discussion of drug product that had already been manufactured and potentially distributed using untested (b)(4). There is no mention of an impact assessment or of any market action.

While your response states that you will reformulate your finished drug products to remove (b)(4), it lacks a retrospective assessment with supporting analytical testing for products containing materials at high risk for (b)(4) contamination that are still on the market and within expiry. Furthermore, your response did not include an assessment of your drug products to identify other components at risk for (b)(4) contamination and proposed corrective actions. Your response also lacks your interim plans, controls, or risk-mitigation strategies until you reformulate your finished drug products.

Identity testing for (b)(4) and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for (b)(4) levels. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to ensure the acceptability of these components for use in the manufacture of your drug products.

The use of ingredients contaminated with (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4) to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high risk for (b)(4) contamination at (b)(4)

In your response to this letter, provide:

• A commitment to provide (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4).
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) contamination (including, but not limited to, (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
• A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your suppliers’ COAs instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your suppliers’ results through initial validation and periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of (b)(4), and certain additional high-risk components, we note that this includes the performance of parts A, B, and C of the USP monograph.
• The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine their acceptability for use in manufacturing.
• 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 components you use to manufacture your drugs.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.

3. 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 QU did not adequately exercise its authority and responsibilities, including but not limited to, implementing effective procedures and conducting adequate oversight of the drug products you manufacture. For example, your QU failed to ensure:

• Establishment of adequate procedures describing their roles, responsibilities, authorities, and oversight (e.g., production personnel perform functions that should be QA responsibilities (21 CFR 211.22(a) and 21 CFR 211.22(d)).
• That production and process control procedures are designed to assure the quality of drug products (e.g., completion of bulk hold time validation studies) (21 CFR 211.100(a)).

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 that your QU is given the authority and resources to function effectively. The assessment should also include but not be limited to:

• A determination of whether procedures used by your firm are robust and appropriate
• 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 products

(b)(4)

FDA identified significant concerns regarding the (b)(4), which appear to operate as closely integrated entities despite maintaining separate corporate identities. Both firms share the same physical location, use common manufacturing operations (utilities, equipment, document management system), and employ overlapping personnel, including key management oversight positions. This level of operational

integration raises questions about the independence of your respective quality systems and regulatory compliance programs. Given that (b)(4), the shared resources and management structure between your firms create the potential for a risk that compliance deficiencies may be transferred or propagated across both organizations. The lack of clear operational separation between (b)(4) diminishes confidence in your ability to maintain independent quality-assurance functions and to implement effective corrective-action systems.

Clarify the nature of this relationship and demonstrate how each entity maintains distinct and adequate control over its manufacturing operations, quality systems, and regulatory compliance responsibilities.

CGMP Consultant Recommended

We acknowledge that you have engaged a consultant to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should be qualified as set forth in 21 CFR 211.34 and should perform a comprehensive six-system audit of your entire operation for CGMP compliance, and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

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.

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on January 9, 2026.

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 VeganicSKN Limited, located at 81 Shettleston Street, Unit III, Rocklea, Queensland, 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 with an opportunity to address the deficiencies above. 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 [email protected]. Identify your response with FEI 3024609429 and ATTN: Yvette Johnson.

Sincerely,
/S/

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