WARNING LETTER
Wuhan Chinese Moxibustion Technology Dev. Co., Ltd. MARCS-CMS 537648 —
- Recipient:
-
Recipient NameMr. Jinlong Fu
- Wuhan Chinese Moxibustion Technology Dev. Co., Ltd.
Wuhan Pharmaceutical Industry Park
East Lake High-Tech Development District, Miaoshan
Wuhan, Hubei
430223
China
- Issuing Office:
- Center for Drug Evaluation and Research
United States
| |
10903 New Hampshire Avenue Silver Spring, MD 20993 |
Via UPS Warning Letter 320-18-20
Return Receipt Requested
December 18, 2017
Mr. Jinlong Fu
President
Wuhan Chinese Moxibustion Technology Dev. Co., Ltd.
Wuhan Pharmaceutical Industry Park
East Lake High-Tech Development District, Miaoshan
Wuhan, Hubei, 430223
China
Dear Mr. Fu:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Wuhan Chinese Moxibustion Technology Dev. Co., Ltd., at Wuhan Pharmaceutical Industry Park, East Lake High-Tech Development District, Miaoshan, Wuhan, Hubei, from May 22 to 26, 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 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 reviewed your June 19, 2017 response in detail. Your response is inadequate because you did not provide sufficient detail or evidence that your proposed corrective actions will bring your operations into compliance with CGMP.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. 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, and the authority to review all production records to assure that no errors have occurred, or, if errors have occurred, that they have been fully investigated. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(a) and (d)).
Your firm lacked an adequate quality control unit. For example, your quality control unit did not adequately review completed production records prior to drug product release.
You also failed to establish adequate written procedures for numerous responsibilities of the quality control unit, such as CGMP training, change control, annual product reviews, recalls for U.S. products, and various other basic drug manufacturing operations.
In response to this letter, provide the following:
- your corrective actionsto ensure that the roles and responsibilities of your quality control unit are clearly defined and established to assure the quality control unit has the appropriate authority and resources needed to carry out its responsibilities; and
- copies of the procedures established by your quality control unit to monitor drug product quality during your manufacturing operations.
2. Your firm failed to prepare master production and control records designed to assure uniformity from batch to batch (21 CFR 211.186(b)).
Your firm lacked product-specific master production and control records that included, for example, (b)(4) speed, (b)(4) time, and the order of component addition for your (b)(4)((b)(4) Patch). Your production records also lacked usage instructions for the (b)(4) and (b)(4) that you used to apply active pharmaceutical ingredient (API) (b)(4) solution on (b)(4) Patch (b)(4).
In response to this letter, provide your established master production and control records for the (b)(4) Patch that fully document each significant and validated manufacturing step, and provide one executed batch record for the (b)(4) Patch.
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)).
Your (b)(4) Patches claim (b)(4)% (b)(4) as the active ingredient, but you indicated that your (b)(4) testing for finished patches relies on qualitative methods that cannot measure and quantify the (b)(4) content in the product. Moreover, our review of (b)(4) Patch batch production records showed no test results for (b)(4) API in released batches (b)(4), (b)(4), and (b)(4).
In response to this letter, provide your corrective action plan to ensure that all drug product batches meet pre-established specifications before you release them. Provide procedures and validated testing method(s) for each release test, including quantitative methods for (b)(4) API content.
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 manufacturing process for (b)(4) Patches. Your firm lacked an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. 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/downloads/drugs/guidances/ucm070336.pdf.
In response to this letter, provide your validation plan for ensuring an ongoing state of control. Include a timeline for performing process performance qualification (PPQ) for all drug products, and describe your approach for monitoring batch-to-batch variations on an ongoing basis.
5. 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)).
The (b)(4) in your (b)(4) materials workshop were rusted, and paint on the (b)(4) and (b)(4) chute of the (b)(4) machine used to (b)(4) components was chipped.
In response to this letter, provide:
- your updated procedures for maintaining, cleaning, and sanitizing all equipment used in the manufacture of your drugs; and
- evidence to show that maintenance and cleaning procedures are effective and sustainable, including your cleaning validation protocol and your evaluation of the results to show that your procedures are adequate.
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 executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
(b)(4) Patch Label
Lastly, during the inspection, investigators collected labeling for your (b)(4) Patch. Drug products such as the (b)(4) Patch intended for external analgesic indications such as the relief of pain are being evaluated as part of the Over-the-Counter (OTC) Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for OTC External Analgesic Drug Products (48 Federal Register (FR) 5852, February 8, 1983) if they meet each condition in the TFM, and each general condition in 21 CFR 330.1.
Pending a final monograph/rule, FDA does not intend to pursue regulatory action against products marketed in conformance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1. Such marketing, however, is subject to the risk that a final rule may require reformulation, relabeling, or FDA approval through the “new drug” procedures of the FD&C Act section 505.
We note that the labeled active ingredient, (b)(4), falls below the level proposed as safe and effective in the TFM. The TFM includes this ingredient in a dosage range of (b)(4)–(b)(4)% (48 FR 5852 at 5868), while the strength of (b)(4) on your product label is declared as (b)(4)%.
Some of your labeled inactive ingredients, such as (b)(4), are not included in FDA’s inactive ingredient database for approved drug products; nor are we aware of these ingredients being used as inactive ingredients in any OTC drug product.
We remind you that it is your responsibility to ensure your product contains only suitable inactive ingredients that are safe in the amounts administered and do not interfere with the effectiveness of the preparation or with suitable tests or assays to determine if the product meets its professed standards of identity, strength, quality, and purity (21 CFR 330.1(e)).
Conclusion
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 October 19, 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 Wuhan Chinese Moxibustion Technology Dev. Co., Ltd., Wuhan Pharmaceutical Industry Park, East Lake High-Tech Development District, Miaoshan, Wuhan, Hubei 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:
Carrie Ann Plucinski
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Please identify your response with FEI 3004859058.
Sincerely,
/S/
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research