- Guangdong Zhanjiang Jimin Pharmaceutical Co., Ltd.
59 South Renming Road
Zhangjiang City, Guangdong Province, P.R.
- Issuing Office:
- Center for Drug Evaluation and Research
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10903 New Hampshire Avenue
Silver Spring, MD 20993
Via UPS Warning Letter 320-18-04
October 30, 2017
Manager of Marketing
Guangdong Zhanjiang Jimin Pharmaceutical Co., Ltd.
59 South Renming Road
Zhangjiang City, Guangdong Province, P.R. 524001
Dear Mr. Feng:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Guangdong Zhanjiang Jimin Pharmaceutical Co., Ltd., at No. 59 South Renming Road, Zhangjiang City, Guangdong, from May 15–19, 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).
In addition to the CGMP violations, your firm also manufactures and distributes a drug product for over-the-counter (OTC) use that violates sections 502 and 505 of the FD&C Act, 21 U.S.C. 352 and 355. A discussion of these violations is included below.
We received your response on August 16, 2017, and reviewed it in detail.
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 (21 CFR 211.22(a)).
You manufacture a topical OTC drug product labeled as containing the active ingredient hydrocortisone. During our inspection, our investigators reviewed records showing that the active pharmaceutical ingredient (API) actually used in this product was dexamethasone acetate—a different API. When our investigator inquired about the incorrect API, your firm stated that there was a translation mistake, and the two API were believed to be the same ingredient. Your quality unit approved multiple lots of this drug product for distribution to the United States containing the incorrect active ingredient.
You recalled all lots of this drug distributed to the U.S. on August 30, 2017. However, you have not provided details of an investigation of the failure of your quality unit and your action plan to prevent recurrence. You also have not provided details of an evaluation to ensure all the drug products you released for distribution to the U.S. were manufactured with appropriate components.
2. Your firm does not 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)).
Your firm failed to test your drugproducts for identity and strength of active ingredients prior to release and distribution. Testing your active ingredients is essential to ensuring the drug products you manufacture meet their established specifications for chemical attributes they purport to possess.
3. 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)).
You have not validated the processes used to manufacture your drug products. You did not perform process performance qualification studies, and 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 elements of process validation at http://www.fda.gov/downloads/Drugs/.../Guidances/UCM070336.pdf.
Inadequate response and CGMP consultant recommended
Your August 16, 2017, response to FDA’s inspectional observations was inadequate and did not provide sufficient evidence of corrective actions to bring your operations into compliance with CGMP. For example, you failed to provide:
- The quality control test methods and specifications used to analyze each drug product batch prior to a batch release decision, including both chemical and microbial quality attributes.
- A clear commitment to test all drug products for identity and strength of active ingredients and all other appropriate quality attributes, including total count and objectionable microorganisms.
- Specific timelines for process performance qualification for each of your drug products, and a detailed summary of your approach for routinely monitoring intra-batch and inter-batch variations.
Based upon the nature of the violations, 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.
Unapproved New Drug and Misbranding Charges
The following statement that appears on your Piyanping Anti-Itch Lotion product demonstrates the intended use of this product. This statement is not inclusive of all claims demonstrating the product’s intended use.
“Temporarily relieves itching associated with minor skin irritations, inflammation, & rashes.”
Based upon the above claim, Piyanping Anti-Itch Lotion is a drug within the meaning of section 201(g)(1)(B) of the FD&C Act 21 U.S.C. 321(g)(1)(B)), because it is intended for use in the diagnosis, treatment, or prevention of disease, and under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C) because it is intended to affect the structure or function of the body. Specifically, it is intended as an external analgesic.
Drug products such as Piyanping Anti-Itch Lotion, intended for external analgesic indications such as the relief of itching, are being evaluated as part of the 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 External Analgesic Drug Products for Over-the-Counter (OTC) Human Use (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 and/or relabeling or FDA approval through the “new drug” procedures of the FD&C Act section 505.
However, your product is not formulated in conformance with the TFM. According to its label, Piyanping Anti-Itch Lotion contains hydrocortisone 1% as its active ingredient, when in fact, the active ingredient is dexamethasone acetate. During the FDA inspection conducted May 15–19, 2017, our investigator reviewed the batch record and finished product testing record for Piyanping Anti-Itch Lotion and noted dexamethasone acetate as the active ingredient in this product. When our investigator questioned your firm about the discrepancy between active ingredients from the label versus batch and finished product testing records, they were told that there was a translation mistake where firm management had thought hydrocortisone was the same material as dexamethasone. Your firm further explained that they had always purchased dexamethasone acetate for use in Piyanping Anti-Itch Lotion and had never purchased hydrocortisone API. Dexamethasone acetate is not in the OTC Drug Review for any indication, including external analgesic antipruritic uses. Further, we are not aware of any evidence that a product formulated like Piyanping Anti-Itch Lotion was commercially available in the United States on or before the inception of the OTC Drug Review or otherwise eligible for inclusion in the ongoing rulemakings, in accordance with existing regulations 21 CFR 330.10(a)(12) and 330.14.
Piyanping Anti-Itch Lotion, as formulated and labeled, is a “new drug” within the meaning of section 201(p) of the FD&C Act 21 U.S.C. 321(p) because it is not generally recognized among scientific experts as safe and effective for uses described in its labeling. “New drugs” may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act 21 U.S.C. 355 is in effect for the drug. Piyanping Anti-Itch Lotion is not the subject of an approved new drug application; therefore, its marketing in the United States is prohibited under section 301(d) of the FD&C Act 21 U.S.C. 331(d) and violates section 505 the FD&C Act 21 U.S.C. 355.
Additionally, Piyanping Anti-Itch Lotion is misbranded under section 502(a) of the FD&C Act 21 U.S.C. 352(a) because its labeling is false and misleading as the formulation differs from what is stated on its label as described above.
Lastly, we note that your product, Shennong Analgesic Plaster, includes the active ingredient methyl salicylate at a dosage range of 1.4%, which falls below what has been proposed in the External Analgesic TFM. The TFM proposes methyl salicylate in a dosage range of 10–60% (48 FR 5852, 5868).
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 August 21, 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 Guangdong Zhanjiang Jimin Pharmaceutical Co., Ltd. at No. 59 South Renming Road, Zhangjiang City, Guangdong, 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.
Daniel W. Brisker
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 3004060039.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research