Hangzhou Facecare Cosmetics Co., Ltd. MARCS-CMS 537146 —
- Delivery Method:
Recipient NameMr. Zhigang Wu
- Hangzhou Facecare Cosmetics Co., Ltd.
755 Yinhai Road, HEDA
- Issuing Office:
- Center for Drug Evaluation and Research
10903 New Hampshire Avenue
Silver Spring, MD 20993
Via UPS Warning Letter 320-18-09
November 17, 2017
Mr. Zhigang Wu
Hangzhou Facecare Cosmetics Co. Ltd.
755 Yinhai Road, HEDA
Hangzhou, Zhejiang, China 310018
Dear Mr. Wu:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Hangzhou Facecare Cosmetics Co., Ltd. at 755 Yinhai Road, HEDA, Hangzhou, from June 19 to 22, 2017.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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 July 12, 2017, response in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
You released over-the-counter (OTC) drug products without adequate acceptance testing for conformance to specifications, including identity and strength. During the inspection, you could not provide analytical data to support the release of your OTC drug products.
Your response stated that you or a contract testing laboratory currently test active ingredient content prior to release of OTC drug products. You also provided results for two finished drug product lots tested by a contract testing laboratory after FDA’s inspection of your facility.
2. Your firm failed to test samples of each component for conformity with all appropriate written specifications for identity, purity, strength, and quality (21 CFR 211.84(d)(1),(2)).
You did not adequately test incoming active pharmaceutical ingredients and other components used in manufacturing your drug products for adherence to appropriate quality attribute specifications.
For example, your procedures did not include requirements for identity testing of each incoming raw material lot. You only required routine incoming testing for appearance, heavy metals, and microbial attributes.
Your response stated that you currently test raw materials to ensure specifications are met before release for manufacturing. You also provided results for four batches of active ingredients tested by a contract testing laboratory after FDA’s inspection of your facility.
3. Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
During the inspection, our investigator found that you shipped OTC drug products to the United States without expiration dates, and you did not have stability data to demonstrate these products meet their specifications (e.g., active ingredient content) throughout their shelf lives.
Your response stated “As we understand, our customers conduct testing to confirm stability and expiration dating.” You also indicated that you were in the process of contacting your customers to confirm responsibilities and OTC drug product expiration dating.
Your July 12, 2017, response to FDA’s inspectional observations was inadequate. You did not provide sufficient evidence that you are taking corrective actions to bring your operations into full compliance with CGMP. For example, you failed to provide:
- The quality control test methods and specifications used by your firm (or a contract laboratory) to analyze each drug product batch prior to a batch release decision.
- A summary of test results obtained from testing all in-date drug products for United States distribution for identity and strength of active ingredients, and all other appropriate quality attributes (including total count and objectionable microorganisms).
- Quality control release specifications for all incoming components, and the tests you perform for each lot.
- A summary of test results obtained from (b)(4) testing of all your incoming components to validate vendors’ certificates of analysis. You also did not commit to test each incoming component batch for identification.
- A summary of your procedures (e.g., qualification, audit, delineation of responsibilities) for qualifying and overseeing the adequacy of contract facilities that test the drug products you manufacture.
- Stability data to demonstrate that all drug products distributed to the United States meet their specifications throughout their assigned shelf lives, and your standard operating procedure (SOP) describing the ongoing stability program.
- A comprehensive assessment of your adherence to CGMP requirements, and a CAPA plan to assure full remediation.
CGMP consultant recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant, qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
Responsibilities as a contractor
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.
You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document, Contract Manufacturing Arrangements for Drugs: Quality Agreements, at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM353925.pdf.
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.
FDA placed your firm on Import Alert 66-40 on September 14, 2017.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in FDA continuing to refuse admission of articles manufactured at 755 YinHai Road, HEDA, Hangzhou, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of 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).
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. 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 or mail your reply to:
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
Please identify your response with FEI 3008655176.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research