Island Kinetics, Inc. d.b.a. CoValence Laboratories（FDA Ref. No.: 320-26-104）

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-104

July 16, 2026

Dear Mr. Vlcek:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Island Kinetics, Inc. d.b.a. CoValence Laboratories, FEI 3002408934, at 460 S. Benson Ln. Suite 1-3, Chandler, AZ, from January 14 to 23, 2026.

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).

In addition, violations were identified and documented during a review of your product labeling. Based on our review, your TreeActiv Cystic Acne Spot Treatment, Ayadara Warrior Two Acne Spot Treatment, and Skin Script Cranberry Turnover Peel drug products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of section 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a), 331(d). In addition, TreeActivCystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introducing or delivering these misbranded products for introduction into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.

We reviewed your February 12, 2026, 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 establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

Lack of Process Validation

You lacked process validation data for all your over-the-counter (OTC) drug products to demonstrate that your manufacturing process is reproducible and controlled to consistently yield drug products of uniform character and quality. For example, the inspection documented that OTC Formula (b)(4), Finished Lots/Bulks (b)(4) and OTC Formula (b)(4), Finished Lots/Bulks (b)(4) were released without process validation.

Our inspection also documented that your firm failed to perform process validation at the actual commercial manufacturing (b)(4) of (b)(4) for OTC Formula (b)(4). You routinely operated the (b)(4) at this (b)(4) which exceeded the qualified limit of (b)(4). Your director of quality confirmed that no process validation had been performed at the actual operating (b)(4) of (b)(4) for OTC Formula (b)(4).

In your response, you indicate that since July 16, 2025, drug products manufactured and released were covered by a process validation protocol. You also commit to execute three qualification batches for OTC Formula (b)(4) by February 2026.

Your response is inadequate because you did not address batches released prior to July 16, 2025 that may not be covered by a process validation protocol. Additionally, you did not provide your interim plan for drugs distributed before process validation activities are completed to ensure you produce drug products of acceptable quality.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to determine whether an initial state of control has been established.

Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance for industry Process Validation: General Principles and Practices for general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices.

Inadequate Equipment Cleaning Validation

Your firm did not have adequate cleaning validation studies for the equipment used to manufacture OTC drug products. For example, you lacked a documented rationale for the products selected for cleaning validation studies. Additionally, you lacked an analytical method to identify and measure specific drug residues to ensure that the cleaning process is effective in preventing cross-contamination between drug products manufactured on the same equipment.

In your response, you opened a corrective action and preventive action (CAPA) plan for cleaning validation deficiencies. You also commit to engaging a consultant to review the existing cleaning validation package, produce a formal worst-case selection justification, and identify any additional analytical work required.

Your response is inadequate because you did not include a risk assessment of previously distributed OTC drug products, a CAPA plan with clear timelines, and evidence that your current cleaning procedures are effective for any of the equipment used in OTC drug product manufacturing at your facility. Furthermore, your response lacks a plan to develop a residue-specific analytical method capable of confirming removal of worst-case drug residues.

Inadequate (b)(4) System Validation

Your firm modified your (b)(4) system (number (b)(4)) in October 2024 by adding a production point of use in the (b)(4) area and replacing the (b)(4) tank with a (b)(4) tank without adequate requalification.

Additionally, your contract testing laboratory reported multiple (b)(4) results exceeding United States Pharmacopeia (USP) specifications for (b)(4) samples from your (b)(4) system points of use which you failed to investigate or remediate.

(b)(4) must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. The lack of adequate (b)(4) system validation provides no assurance the system performs as intended. Your use of (b)(4) from an unvalidated system in pharmaceutical manufacturing can adversely affect drug product quality and patient safety.

Biofilm formation is also a significant concern in (b)(4) systems operating at (b)(4) as biofilms can lead to undesirable levels of microorganisms and endotoxins. Your (b)(4) system material selection and operating (b)(4) may present challenges for maintaining adequate sanitization and microbiological control necessary to ensure that your (b)(4) meets established pharmaceutical specifications.

In your response, you commit to engaging a consultant to evaluate whether revalidation of (b)(4) system (number (b)(4)) was required. You also commit to updating your change control form to require a risk assessment for future system changes. Additionally, you opened a CAPA for investigations, committed to revising the investigation form and providing training to staff.

Your response is inadequate because you did not provide a detailed (b)(4) system validation plan and an interim plan to ensure that the (b)(4) is suitable for its intended use. You also did not adequately address the recurring (b)(4) contamination in your (b)(4) system. In addition, you did not provide documentation to support your proposed corrective actions. These concerns indicate that microbial contamination and organic impurities in your (b)(4) system were not adequately controlled.

In response to this letter, provide:

• 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 and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

• A timeline for performing process performance qualification 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 protocol(s), and written procedures for qualification of equipment and facilities.

• A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.

• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces (b)(4) that meets (b)(4), USP monograph specifications and appropriate microbial limits.

• A comprehensive remediation plan for the design, control, and maintenance of the (b)(4) system, including:
  o a comprehensive evaluation of vulnerabilities of (b)(4)-system design and control and summarize all deficiencies found in the system. The summary should, at a minimum, describe various system characteristics that were assessed for adequacy (for example, system (b)(4), materials of construction, slope, identified dead-legs, stagnant locations, unsanitary fittings, flow velocity, maintenance requirements).
  o A CAPA plan that corrects all (b)(4)-system design and control deficiencies. Include your plans for new system installation, or extensive design remediation (for example, removal of all dead-legs); preparation of a system-validation protocol; and the planned timeline for completion of thorough (b)(4)-system validation studies.

• Your plans for improved (b)(4)-system monitoring, including but not limited to the routine microbial testing of (b)(4) and appropriate limits (objectionable microbes, total count alert/action limits) to ensure the (b)(4) acceptability for use in each batch of drug product produced by your firm. Ensure that your (b)(4) total-count limits are appropriately stringent, in view of the intended use of each of the products produced by your firm.

• A detailed risk assessment addressing the potential effects of the observed (b)(4)-system failures on the quality of all drug product batches currently in U.S. distribution. Specify the actions you will take in response to the risk assessment, such as customer notifications and product recalls.

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).

Your firm failed to adequately investigate viscosity failures identified during stability testing of distributed OTC drug products. Specifically, stability testing records documented multiple viscosity out-of-specification (OOS) results without adequate root cause determination, CAPA, or documented justification for the established viscosity specifications.

In your response, you attribute the root cause to lack of procedures for third-party OOS investigations and commit to creating a new SOP and provide staff training.

Your response is inadequate because you did not include a risk assessment of previously distributed products with viscosity OOS results, a CAPA plan with clear timelines, documented justification for your established viscosity specifications, and an assessment of the link between your unvalidated processes, unqualified equipment, and the observed viscosity failures.

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 CAPA plans.

You are also responsible for ensuring your manufacturing process is reproducible and under control, and for determining any potential correlation between discrepancies and OOS results obtained with your critical manufacturing parameters.

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 retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for US 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.
  o Your retrospective review should include all test results received from your third-party laboratory.

• A comprehensive review and remediation plan for your OOS and out-of-limit (OOL) 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 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.

• Complete investigations into all batches with microbial contamination whether or not later invalidated. The investigations should detail your findings regarding the root causes of the contamination.

Violations of the Federal Food, Drug, and Cosmetic Act

The following are violations identified during our review. As a reminder, this is not an all-inclusive list of violations that may exist in connection with your products or operations.

Unapproved New Drug Violations

Based on a review of your product labeling, your TreeActiv Cystic Acne Spot Treatment, Ayadara Warrior Two Acne Spot Treatment, and Skin Script Cranberry Turnover Peel are drugs under section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B) because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body. Examples from your product labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of these products as a drug include, but may not be limited to, the following:

TreeActiv Cystic Acne Spot Treatment

“CYSTIC ACNE SPOT TREATMENT…DRUG FACTS…USE for the treatment of acne…is the most effective treatment for severe and cystic acne.” [from the product label]

Ayadara Warrior Two Acne Spot Treatment

“CYSTIC, HORMONAL, & SEVERE ACNE SPOT TREATMENT…DRUG FACTS…USE for the treatment of acne…treatment that minimizes pimples, zaps zits, and helps prevent future breakouts. [from the product label]

Skin Script Cranberry Turnover Peel

“Benefits: Contains 20% salicylic to dry oil and reduce bacterial attacks…Cranberry is an excellent antioxidant to reduce inflammation associated to acne.” [from the product label]

TreeActiv Cystic Acne Spot Treatment, Ayadara Warrior Two Acne Spot Treatment, and Skin Script Cranberry Turnover Peel are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p) because they are not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in their labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355 are in effect for these drug products identified above. Accordingly, these products are unapproved new drugs. The introduction or delivery for introduction into interstate commerce of these unapproved new drug products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).

We note that under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription acne treatment drug products, such as your TreeActiv Cystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment, in order to be GRASE and not new drugs, the products must, among other things, conform to the conditions in the applicable OTC monograph, here M006: Topical Acne Drug Products for Over-the-Counter Human Use (hereinafter “M006”).1 However, TreeActiv Cystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment, and do not conform to the conditions specified in M006 for the reasons described below.

Your TreeActiv Cystic Acne Spot Treatment product as labeled, includes indications that do not comply with the permitted indications for an acne treatment drug product. For example, claims such as “CYSTIC ACNE SPOT TREATMENT” and “most effective treatment for cystic and severe acne” go beyond merely describing the general intended uses for an acne treatment drug product and are not permitted under M006.

Similarly, Ayadara Warrior Two Acne Spot Treatment, as labeled, includes indications that do not comply with the indications for an acne treatment drug product. For example, claims such as “CYSTIC, HORMONAL, & SEVERE ACNE SPOT TREATMENT” go beyond merely describing the general intended uses for an acne treatment drug product and are not permitted under M006.

Thus, your TreeActiv Cystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment products do not comply with the applicable conditions specified in M006 and have not and have not otherwise been found GRASE.2 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no applications in effect for these products, these products are unapproved new drugs.

Misbranded Drug Violations

Additionally, TreeActiv Cystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee) because these products are nonprescription drugs, subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.

The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

Repeat Violations at Facility

In previous inspections, conducted in 2016 and 2020, FDA cited similar CGMP violations. You proposed specific remediation for these violations in your responses. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

CGMP Consultant Recommended

Because you failed to correct repeat violations, 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.

Cosmetics Manufactured for Distribution in the United States

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.

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 3002408934 and ATTN: Chhaya Shetty.

Sincerely,
/S/

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

/S/

Tina Smith
Captain, U.S. Public Health Service
Director
Office of Unapproved Drugs & Labeling Compliance
Office of Compliance
Center for Drug Evaluation and Research

____________________

1 M006 reflects the conditions as set forth in the relevant final orders established and in effect under section 505G; see Order OTC000013, available at FDA’s website OTC Monographs @ FDA [https://dps.fda.gov/omuf].

2 FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that TreeActiv Cystic Acne Spot Treatment and Ayadara Warrior Two Acne Spot Treatment products are GRASE for use under the conditions prescribed, recommended, or suggested in their labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).