Cohere Beauty

April 15, 2024 Dear Mr. Staples:

The U.S. Food and Drug Administration inspected your drug manufacturing facility, Health Specialty, FEI 3005945400, at 8339 Allport Ave, Santa Fe Springs, California, from November 27 to 30, 2023.

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 December 21, 2023, response to our Form FDA 483 in detail and 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 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)).

Your firm failed to validate the manufacturing processes for your over-the-counter (OTC) drug product (b)(4). During the inspection, you could not provide process validation studies for the (b)(4) drug product. You manufactured, released, and distributed at least (b)(4) lots of (b)(4) in 2023, and you failed to demonstrate that your manufacturing process were controlled to consistently yield a drug product of uniform character and quality.

In your response, you stated that you will analyze release data to ensure products still in distribution are safe and effective, and then provided a summary of release testing data of assay and microbial enumeration results for the (b)(4) batches.

Your response is inadequate because you did not provide adequate assurance that the batches released to the U.S. market, manufactured without validation, are of the appropriate identity strength, quality, and purity they purport or are represented to possess. Furthermore, your response lacked a plan to monitor the stability of (b)(4) drug product and handle complaints to address products remaining on the U.S. market.

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 includes intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluates 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 the FDA’s guidance document 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/media/71021/download.

In response to this letter, provide:

A list of (b)(4) drug product batches remaining in the U.S. market and within expiry including, but not limited to, batch/lot numbers, distribution dates, and expiration dates.

A comprehensive plan on the oversight of (b)(4) drug product remaining in the U.S. market including, but not limited to, responsibilities for reserved samples collection and storage, stability program, and complaint receipt and handling.

Your action plan to address any product quality risks associated with batches within expiry on the U.S. market, including potential customer notifications and recalls.

2. 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) lacked adequate oversight for the manufacture of your OTC drug products. For example,

Your QU failed to ensure that analytical methods used to test your components, such as (b)(4), and (b)(4) were validated or verified.

Your QU failed to adequately investigate an out-of-specification (OOS) test result for the (b)(4) of your bulk drug product (b)(4), batch (b)(4). Your investigation only focused on reviewing formulation and customer complaints but did not adequately investigate the root cause.

You failed to fulfill the commitments you stated would be completed before you resumed the manufacture, release, and distribution of your drug products. During the June 20, 2023, regulatory meeting held with your firm, you committed to ceasing distribution of all finished drug products until your test methods were validated or verified, and your contract testing laboratory was qualified. Despite these commitments, you manufactured, released, and distributed at least (b)(4) lots of hand sanitizer drug products and (b)(4) lots of (b)(4) drug products between June 28, 2023, and October 26, 2023. Subsequent to the regulatory meeting, you also stated that you ceased accepting new OTC drug product orders. Yet, you accepted at least (b)(4) purchase orders for the (b)(4) drug product on September 26, 2023.

In response to this letter, provide:

A complete list of all drug product batches remaining in the U.S. market and within expiry including, but not limited to, batch/lot numbers, distribution dates, and expiration dates.

A comprehensive plan on the oversight of drug products remaining in the U.S. market. For each drug product that is within expiry, provide detailed information including, but not limited to, responsibilities for reserved samples collection and storage, stability program, and complaint receipt and handling.

Your action plan to address any product quality risks associated with batches within expiry on the U.S. market, including potential customer notifications and recalls.

Your firm’s quality systems are inadequate. See the 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.

Your inspectional history and significant findings in this letter indicate that your QU is not fully exercising its authority and/or responsibilities. If, in the future, your firm decides to resume manufacturing drug products for the U.S. market, your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.

In a previous inspection conducted in December 2022, the FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response and during the regulatory meeting with the FDA. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

We acknowledge your commitment to cease production of drugs at this facility.

If you plan to resume manufacturing drugs for the U.S. market at your facility or move any of your operations to a new location, notify this office prior to resuming your operations. Should you resume manufacturing drugs, 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. The qualified consultant should also 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 the 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.

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 the FDA to withhold issuance of Export Certificates. The 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.

Please identify your response with the unique identifier: CMS# 675475.

Send your electronic response to ORAPHARM4_Responses@FDA.HHS.GOV with ATTN: CDR Steven E. Porter, Jr. or mail your written response to:

CDR Steven E. Porter, Jr. Director, Division of Pharmaceutical Quality Operations IV U.S. Food & Drug Administration 19701 Fairchild Road Irvine, California 92612-2506

If you have questions regarding this letter, please contact Compliance Officer LCDR Rumany Penn at (949) 608-4409, or by email at Rumany.Penn@fda.hhs.gov.