WARNING LETTER
Imperial Palace Commodity -Dongguan- Co., Ltd.
MARCS-CMS 692842 —
January 27, 2025
Delivery Method:
VIA Electronic Mail
Reference #:
320-25-33
Product:
Drugs
Recipient:
Recipient Name
Mr. Alan Xu
Recipient Title
General Manager
Imperial Palace Commodity -Dongguan- Co., Ltd.
No. 523 1st Liudong Road
Changlong Village
Huangjiang Town
Dongguan Shi
Guangdong Sheng
,
523750
China
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
Warning Letter
320-25-33
January 27, 2025
Dear Mr. Xu:
Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our March 4, 2024 request, and subsequent requests, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Imperial Palace Commodity (Dongguan) Co., Ltd., FEI 3014838570, at No. 523 1st Liudong Road, Changlong Village, Huangjiang Town, Dongguang, Guangdong 523750, China.
This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your responses to our 704(a)(4) request do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)).
704(a)(4) Request for Records and Related CGMP Violations
Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:
1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).
Your firm manufactures OTC drug products such as alcohol wipes. Based on the records and information you provided, you did not demonstrate that you have adequately tested incoming components used in the manufacture of your drug products. For example, you failed to conduct adequate identity testing on your incoming components. Additionally, your firm relied on the certificates of analysis (COAs) from your suppliers and failed to establish the reliability of each of your suppliers’ COA for component specifications and characteristics at appropriate intervals.
Glycerin
Information provided indicates that you failed to demonstrate that you adequately test each shipment of each lot of glycerin for identity, a component at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. We note that glycerin is an ingredient used in your alcohol wipe drug products. Identity testing of glycerin, along with other high-risk drug components
1
, includes 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 glycerin lot using the USP identification tests that detects these hazardous impurities, you failed to assure the acceptability of this component for use in the 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.
Ethanol
You also failed to adequately test your incoming component, ethanol, used as an active ingredient in your alcohol wipes, for methanol. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document
Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol
to help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/media/173005/download.
Without adequate testing, you do not have scientific evidence that your incoming components conform to appropriate specifications before use in the manufacture of your 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)).
Process Validation
Based on the records and information you provided, you did not demonstrate that you have adequately validated the manufacturing process for your alcohol wipe drug products. For example, the records you provided to demonstrate your process validation for your drug products, included only reports of analytical test results.
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 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.
Water System Validation
Your firm uses water as a component in your drug products. You have not demonstrated that your firm’s water system has been adequately designed and validated for its intended use. For example, your response states that your water system is qualified only for
(b)(4)
water. In addition, your
(b)(4)
water validation report did not include testing results for total organic carbon. Your firm has not demonstrated that the water is suitable for use and meets the USP
(b)(4)
Water monograph specifications.
3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
Based on the records and information you provided, you did not demonstrate that you used an appropriate test method for microbiological testing as part of your stability program. For example, the records you provided for your stability program identified your microbiological testing method as “Antibacterial efficacy test-refer to USP 40 51>.” You reported results for “total aerobic microbial count,” “coliform bacteria,” and “fungi,” as well as other specified microorganisms, but your results reflect that your methods are not consistent with
USP <51> Antimicrobial Effectiveness Testing
. The methodology described in USP <51> is intended to demonstrate the effectiveness of added microbial preservatives; however, your response states that your drug products do not contain preservatives.
Without appropriate test methods, you do not have scientific evidence to support whether your drug products meet their established microbiological specifications through their labeled expiry.
4. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
The records and information you provided demonstrated that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your drug manufacturing operations. For example, your QU did not adequately exercise its authority over the establishment of controls in your Materials System and Laboratory Control System.
Your QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may not be conducting appropriate oversight regarding CGMP operations. See 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.
CGMP Consultant Recommended
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.
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.
FDA placed products offered for import into the United States from your firm on Import Alert 66-40 on January 23, 2025.
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 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 Imperial Palace Commodity Dongguan Co., Ltd., at No. 523 1st Liudong Road, Changlong Village, Huangjiang Town, Dongguan, Guangdong 523750, China, 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.
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 3014838570 and ATTN: Joel Hustedt.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Registered U.S. Agent
Pro Medical Supplies, Inc.
Mr. Jake Sztejman
Email: Jake.Sztejman@outlook.com
_________________________
1
Components with higher risk of DEG or EG contamination compared to other drug components.
Content current as of:
02/04/2025
Regulated Product(s)
Drugs