Active Cosmetics Manufacturing Inc.

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Active Cosmetics Manufacturing Inc., FEI 3005351079, at 7075 Kingspointe Parkway, Suites 2, 3, 4, and 5, Orlando, from October 27 to 31, 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 November 21, 2025 response to our Form FDA 483 in detail.

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 topical over-the-counter (OTC) drug products, including (b)(4) labeled for use in (b)(4). You failed to adequately investigate out-of-specification (OOS) microbiological test results of your drug products.

You released batches for commercial distribution based on passing retest results, without conducting thorough investigations to determine the root causes of the original results. For example:

Batch (b)(4) was found to contain the objectionable microorganism Staphylococcus aureus.

Batch (b)(4) was found to contain the objectionable microorganism Pseudomonas aeruginosa.

Batch (b)(4) failed the Neogen Soleris Next Generation System test that you claimed assesses total viable count.

Passing retest results alone cannot serve as the basis for invalidating OOS results. As a manufacturer, you have a responsibility to fully investigate aberrant microbial test results that may impact drug product quality. In addition, investigations into microbial contamination should include awareness that microbial contamination is not uniformly distributed.

These findings are indicative of a lack of state of control of your manufacturing processes. We note that your firm has not performed process validation studies to determine whether the processes used to produce your marketed OTC drugs are reliable and reproducible.

In your response, you state you retested reserve samples from affected batches and initiated an investigation. You also revised your OOS procedure to include more detailed guidance on phase I and II investigations, root cause determination, and to assess impact on other batches and procedures.

Your response is inadequate because it lacks a systemic investigation into the root cause of the OOS microbial results. Additionally, your response lacks a comprehensive drug product impact assessment that accounts for potentially impacted drug products within expiry.

It is essential to conduct thorough, well documented, and scientifically sound investigations to identify root causes of OOS results, evaluate all potentially affected batches, and implement timely and effective corrective action and preventive action (CAPA) plans.

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, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for 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 Quality unit oversight of laboratory investigationso Identification of adverse laboratory control trendso Resolution of causes of laboratory variationo Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequate scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediations

A detailed risk assessment addressing the hazards posed by distributing drug products with potentially objectionable contamination. Specify actions you will take in response to the risk assessment, such as customer notifications and product recalls.

A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

A timeline for performing PPQ for each of your marketed drug products. Also provide a risk assessment and any follow-up actions to be taken for the distributed drug products produced without performing any process validation studies.

Process performance protocols, and written procedures for qualification of equipment and facilities.

You failed to adequately validate your alternative rapid microbiological test methods. You use the Neogen Soleris Next Generation System for rapid microbiological testing of your finished drug products (e.g., total aerobic counts, total counts, specified microorganisms) and failed to demonstrate that it was equivalent to or better than United States Pharmacopeia (USP) compendial methods and suitable for its intended use.

You stated that this system was validated by the manufacturer. However, your method did not meet the minimum requirements for adequate identification of objectionable microorganisms and total count quantification.

The microbiological testing methodology uses qualitative pass/fail criteria that do not ensure appropriate quantitative enumeration. The method is inadequate because it does not provide sufficient data on contamination levels, which are essential for trend analysis and evidence-based risk assessment to support quality evaluations and patient safety.

In your response, you acknowledge that you have not validated your alternative rapid microbiological test methods. You state you will fully validate methods used in your alternative rapid microbiological testing within six to eight months.

Your response is inadequate because it fails to address the fundamental gap between qualitative pass/fail criteria and appropriate quantitative enumeration.

Test methods must be validated to show that they are suitable for their intended use and equivalent to or better than applicable USP compendial methods. The reproducibility of your test methods is essential to determine whether your drug products meet established specifications for microbial attributes.

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 comprehensive independent evaluation of microbiological tests methods used to perform total counts and identification to evaluate suitability for intended use, followed by systemic CAPA including, but not limited to:o A comprehensive retrospective evaluation of each test method to determine any inadequacies including, but not limited to, those cited in this letter.o Where a method is found unsuitable for its intended use (e.g., inadequate capacity to accurately enumerate, microbial identification), provide information on a new suitable method that will be employed.o Improved systems to ensure suitability of microbiological test methods in the future before implementation.o Once this full evaluation is complete, provide a summary of findings, data, and all deviations encountered.

Following review by an independent third-party, provide updated validation protocols and final reports that adequately address methods for each product, including specificity, limit of detection, robustness, ruggedness, and repeatability. This should also include an evaluation of whether sample sizes are appropriate. Where you intend to use non-compendial methods, provide studies evaluating the equivalence or superiority of the method to the USP method.

A list of chemical and microbial specifications, including test methods, used to analyze each batch 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 in 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.

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)).

You failed to perform adequate identity testing on each shipment of each lot of incoming components (e.g., (b)(4)) used in the manufacture of your drug products. In addition, you relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.

(b)(4)

You failed to adequately test each shipment of each lot of (b)(4), which you used as inactive ingredients in your drug products, for (b)(4) contamination. Complete identity testing for (b)(4), and certain other high-risk drug components includes a limit test in the USP to ensure that the component meets the relevant safety limits for levels of (b)(4). 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 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, you state that you have conducted a retrospective analysis and intend to have a qualified independent laboratory perform additional analysis. However, you fail to show that the retrospective testing meets full USP compendial requirements for ingredients at high risk for (b)(4) contamination. You also fail to show that the (b)(4) you tested from your current inventory are fully representative of the component lots you used in your drug products that remain within expiry.

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

In response to this letter, provide:

A comprehensive, independent review of your material system, including but not limited to:o evaluating all suppliers of materials (components, containers, and closures) to determine if they are reliable and appropriately qualifiedo an assessment of all materials to determine whether they are consistently of acceptable qualityo a review to ensure assigned expiration or retest dates are appropriate (supported by data)o adequacy of the supplier qualification program, and its selection, qualification, and disqualification provisions

Based on a thorough review, provide a summary of your systemic CAPA to remediate the vendor qualification program and prevent use of unsuitable components, containers, and closures.

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 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 components 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 supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as 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 acceptability for use in manufacturing.

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 evaluate your operations and 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.

In addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act (21 U.S.C. 321(i)). Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act (21 U.S.C. 331(a)), it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.

We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.

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.

After you receive this letter, respond to this office in writing within 15 working days. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices, and/or submit a request to schedule an FDA inspection.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3005351079 and ATTN: Rokhsana Safaai-Jazi.