HTO Nevada, Inc. dba Kirkman

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, HTO Nevada, Inc. dba Kirkman, FEI 3004268965, at 6400 Rosewood Street, Lake Oswego, from August 18 to 22, 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 September 12, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence. Your response is inadequate because, while you indicate that you will no longer manufacture drugs, you did not provide adequate corrective actions and preventive actions (CAPA) for the violations, including addressing whether the drug products will be removed from the market.

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 firm is a contract manufacturer of over-the-counter (OTC) (b)(4) drug products. Your quality unit (QU) did not adequately oversee your drug manufacturing operations. For example, your QU failed to ensure:

Adequate change control procedures, because after reformulating (b)(4) drug products with a new API, your QU released and distributed batches of these drug products with inaccurate labeling, still showing the previous active pharmaceutical ingredient (API). Specifically, (b)(4) was listed on the product labeling, when the drug product actually contained the reformulated API, (b)(4). Thus, your drug product label to contain (b)(4) actually contained (b)(4) (21 CFR 211.22(d)).

Appropriate oversight for contract testing laboratories regarding qualification, method validation, and written agreements describing roles and responsibilities (21 CFR 211.22(a) and 211.22(b)).

Performance of periodic production review at least annually (21 CFR 211.180(e)).

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download for help with implementing quality systems and risk management approaches to meet the requirements of CGMP regulations (21 CFR, parts 210 and 211).

In response to this letter, provide a risk assessment regarding the change in the active ingredient for (b)(4) drug products.

2. 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)).

You lacked process validation data to demonstrate that you have adequately validated the manufacturing processes for drug products. Additionally, your procedures and batch records lack parameters, such as (b)(4), that may impact the quality of your drug products. Furthermore, you failed to adequately qualify and test your (b)(4) system, which is used in the manufacture of the drug products. For example, you did not test your (b)(4) system for (b)(4).

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 must ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies 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 that you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance for industry, Process Validation: General Principles and Practices at https://www.fda.gov/media/71021/download for general principles and approaches that the FDA considers appropriate elements of process validation.

In response to this letter, provide:

A risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.

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

Your firm failed to establish an adequate stability program with data from long-term or accelerated storage conditions, demonstrating that the drug products remain acceptable throughout the labeled expiry period. The stability protocol provided was an incomplete 24-month stability report for (b)(4) that lacked recorded results and the appropriate signatures. Without the appropriate stability studies, you do not have adequate scientific evidence to support that your drug product retains its quality attributes throughout the labeled (b)(4) expiry period.

In response to this letter, provide:

A retrospective risk assessment showing how you will ensure that marketed drug products meet stability specifications throughout their shelf life.

A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your current stability program. Your remediated program should include but not be limited to:o Stability-indicating methodso Stability studies for each drug product in its marketed container/closure system before distribution is permittedo An ongoing program in which representative batches of each product are added to the program each year, to determine if the shelf-life claim remains valido A detailed definition of the specific attributes to be tested at each station (time point)

All procedures that describe these and other elements of your remediated stability program.

A summary of all results obtained from testing retain samples using your remediated stability protocols from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

In a previous inspection, dated March 19, 2019, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

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 evaluating products that remain in distribution.

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.

We acknowledge your commitment to cease production of all drugs at this facility for the U.S. market. In response to this letter, clarify whether you intend to resume manufacturing any drugs at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

Additionally, you remain responsible for the products on the U.S. market through their expiry date, which includes ensuring that you have adequate stability data to support these marketed products.

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 3004268965 and ATTN: Christopher Jenner.