Luen Wah (HK) Medicine Ltd MARCS-CMS 542595 —
- Luen Wah (HK) Medicine Ltd
- Issuing Office:
- Center for Drug Evaluation and Research
10903 New Hampshire Avenue
Silver Spring, MD 20993
Via UPS Warning Letter 320-18-44
Return Receipt Requested
April 06, 2018
Ms. Mimi Shun
CEO and Managing Director
Luen Wah (HK) Medicine Ltd.
12 Ka Yip Street, 412 Room
Paramount Building 406
Chai Wan, Hong Kong Island
Hong Kong SAR
Dear Ms. Shun:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Luen Wah (HK) Medicine Ltd. at 12 Ka Yip Street, Paramount Building 406, 412 Room, Chai Wan, Hong Kong Island, from September 25 to 28, 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 October 17, 2017, response in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. Your firm failed to perform, 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, and for each batch of drug product required to be free of objectionable microorganisms, appropriate laboratory testing, as necessary (21 CFR 211.165(a) and (b)).
Your firm released your over-the-counter (OTC) drug products to the United States market without testing identity and strength of each active ingredient. In addition, you released these drug products without testing for total aerobic microbial count and objectionable micro-organisms. Testing is essential to ensuring that the drug products you manufacture meet established specifications for the chemical and microbial attributes they purport to possess.
Your response states that you will create new sampling procedures for your drug manufacturing processes. Your response is inadequate. Your response failed to provide details for establishing your finished product specifications for your OTC (b)(4) drug products. You also did not provide details for the associated test methods or any comparability studies to demonstrate that your test methods are equivalent to or better than USP test methods. In addition, your response does not address whether your firm will conduct retrospective testing of your retain samples of drug products distributed to the U.S. to assure specifications are met.
In response to this letter, provide your newly-established test methods and specifications intended to analyze each batch of drug product prior to release. Also, provide a summary of your test results obtained from full testing of retains for all batches of your drug products distributed to the U.S. market still within expiry. If you find that you released any batch for which results are out of specification (OOS), indicate the corrective actions you will take, such as customer notifications and product recalls.
2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to establish the reliability of component supplier analyses on which you rely in lieu of certain tests through appropriate validation of the supplier's test results at appropriate intervals. (21 CFR 211.84(d)(1) and (2)).
Your firm failed to test incoming active pharmaceutical ingredients (API) and other components used to manufacture your OTC drug products to determine their identity, purity, strength, and other appropriate quality attributes. Instead, your firm relied solely on certificates of analysis (COA) from unqualified suppliers.
Your response states that you will conduct identity testing on incoming API and other components, and that you will establish sampling procedures. Your response is inadequate. Your response failed to provide a list of all active ingredients and components to be tested for your OTC drug products. You also did not provide details for the associated test methods for your active ingredients and components demonstrating that your test methods are equivalent to or better than USP methods.
In response to this letter, provide a summary of the test results obtained from fully testing each of your active ingredients and other incoming components to validate suppliers’ COA. In addition, provide your specifications for all API and incoming components. Include a description of the sampling and testing to be performed.
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)).
Your firm has not established a stability program. You lack data to demonstrate that the chemical and physical properties of your OTC (b)(4) drug products will remain acceptable throughout their labeled (b)(4) expiry period.
Your response states that you will perform accelerated stability testing and establish a stability program. Your response is inadequate. Your response failed to include your stability protocols which includes timelines. You also failed to address whether you will perform a risk assessment or conduct testing to address the drug products distributed to the US with an expiry not supported by stability data.
In response to this letter, provide stability data to demonstrate that all your OTC drug products distributed to the U.S. meet their specifications throughout their assigned shelf lives. Also, provide your procedure describing your ongoing stability program.
4. 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 has not validated the processes used to manufacture your drug products. You failed to perform process qualification studies, and lacked an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
Your response states that you will evaluate your manufacturing processes to determine the critical production steps. You also state that you will perform concurrent validation of your manufacturing processes which will include modification of your master batch records. Your response is inadequate. Your response failed to provide your validation protocols. You also did not provide your revised batch records based on your newly-established manufacturing process parameters.
In response to this letter, provide timelines for process performance qualification for each of your (b)(4) drug products. In addition, provide a detailed summary of your approach for routinely monitoring intra- and inter-batch variation. Also provide drafts of your revised batch record with newly-defined process parameters, such as (b)(4) times, (b)(4) speeds, temperatures, and bulk hold times.
See FDA’s guidance document, Process Validation: General Principles and Practices, for approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf.
CGMP consultant recommended
We acknowledge that your firm was working with a consultant during the inspection. However, 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 violations and ensuring ongoing CGMP compliance.
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 in all your facilities.
FDA placed your firm on Import Alert 66-40 on January 18, 2018.
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 Luen Wah (HK) Medicine Ltd, 12 Ka Yip Street, Paramount Building 406, 412 Room, 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:
Ms. LaKeesha Foster
Consumer Safety Officer
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: 3004962092.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research