Eksa Mills S.A. de C.V.

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Eksa Mills S.A. de C.V., FEI 3016927597, at E. Parque Industrial Carretera Federal Mexico Veracruz 1056, Heroica Puebla De Zaragoza, Puebla, from April 18 to April 19, 2022.

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 April 24, 2022, response to our Form FDA 483 in detail. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

Your firm manufactures over-the-counter (OTC) drug products such as (b)(4) and (b)(4).1 You also manufacture commercial chemical (b)(4) solution products for the (b)(4) industry on the same manufacturing equipment as your OTC drug products. Inadequate removal of residues from manufacturing equipment during cleaning can lead to contamination of drug products subsequently manufactured on the non-dedicated equipment. Further, your firm did not maintain written cleaning procedures or equipment use logs for the (b)(4) tanks used to manufacture drug products.

It is unacceptable as a matter of CGMP to continue manufacturing drugs using the same equipment that you use to manufacture commercial (b)(4) solutions or other non-pharmaceutical products due to the risk of cross-contamination.

In response to this letter, discontinue manufacturing drugs on shared equipment with non-pharmaceuticals in your facility. If you intend to resume manufacture both pharmaceutical and non-pharmaceutical products at your facility, provide a plan to show how you will separate the areas in which you will maintain dedicated manufacturing equipment for your pharmaceutical manufacturing and industrial product manufacturing operations.

In addition, conduct a risk assessment for all drugs you have previously manufactured on equipment shared with non-pharmaceutical products. For each product, assess the risk of potential contamination due to shared equipment and provide your plans for addressing the product quality and patient safety risks for any product still in distribution, including potential recalls or market withdrawals.

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) did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure the following:

• Adequate procedures describing roles and responsibilities of the QU, including the handling of vendor qualification, batch release, reserve samples, investigations, complaints, and CGMP training (21 CFR 211.22(a) and (d)). • Adequate testing of your incoming components for identity, purity, strength, and other appropriate quality attributes (21 CFR 211.84(d)(1) and (2)). • Adherence to a stability program (21 CFR 211.166(a)). • Adequate maintenance of batch records (21 CFR 211.188).

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help in 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 your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to: o A determination of whether procedures used by your firm are robust and appropriate o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices o A complete and final review of each batch and its related information before the QU disposition decision o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products

We acknowledge your commitment to cease production of drugs at this facility and that you deregistered your facility as a drug manufacturer. If you plan to resume manufacturing drugs for the U.S. market, notify this office before resuming your operations.

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 assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and evaluates 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.

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 your firm on Import Alert 66-40 on August 12, 2022.

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 Eksa Mills S.A. de C.V., E. Parque Industrial Carretera Federal Mexico Veracruz 1056, Heroica Puebla De Zaragoza, Puebla 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 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 3016927597 and ATTN: Tamara Rosbury.