C&T Dream Co., Ltd.

Warning Letter 320-24-33

April 11, 2024 Dear Mr. Anh:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, C&T Dream Co., Ltd., FEI 3012668529, at 60 Baekseokgongdan 7-Ro, Seobuk-gu, Cheonan-si, Chungcheongnam-do, Republic of Korea, from November 6 to 10, 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 product is 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 have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.

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

Your firm manufactures an over-the-counter (OTC) topical drug product, Dry Skin Healing Ointment. You failed to adequately test your incoming components used in the manufacture of your drug products for identity. For example, your firm failed to adequately test each shipment of each lot of incoming components at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. This includes, but is not limited to, testing of glycerin you use in manufacturing your drug product to determine its appropriate identity. Identity testing for this and certain other high-risk drug components1 include a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. 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 assure the acceptability of these components for use in manufacture of your drug products.

The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.

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

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)).

Your firm failed to adequately validate your production and process controls. As such, you do not have assurance that you are capable of consistently manufacturing an OTC drug product with defined quality attributes.

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 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 FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.

Our investigators observed water damage and mold-like substance in the entrance way of the R&D Center Building. Additionally, the ceiling of the (b)(4)-floor warehouse in the R&D Center Building was actively leaking during the inspection, and our investigators observed that you attached plastic sheeting to the ceiling in attempts to contain the leak. Your R&D Center Building is used in the manufacture and storage of your drug product, including the (b)(4)-floor warehouse for storing packaging components for your drug product.

It is essential that your facility is in a good state of repair and sanitary conditions are maintained to protect drug products from potential routes of contamination.

In a previous inspection, performed July 17 to 21, 2017, 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.

We acknowledge your commitment to cease production of drugs for the U.S. market.

In response to this letter, clarify whether you intend to resume manufacturing drugs for the U.S. market at this facility in the future. 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.

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 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 April 10, 2024.

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 C&T Dream Co., Ltd., at 60 Baekseokgongdan 7-Ro, Seobuk-gu, Cheonan-si, Chungcheongnam-do, 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 3012668529 and ATTN: CDR Frank Verni.