Hangzhou Karic Commodities Co., Ltd. MARCS-CMS 556676 — July 31, 2018

WARNING LETTER

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• Recipient: Mr. Kaimin Bian; Hangzhou Karic Commodities Co., Ltd.; No. 2 Fifth Avenue; West Lake Science and Economic Zone; Hangzhou, Zhejiang; 310030; China

• Issuing Office: Center for Drug Evaluation and Research; United States

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	10903 New Hampshire Avenue Silver Spring, MD 20993

 

Via UPS                                                                                 Warning Letter 320-18-67

Return Receipt Requested

 

July 31, 2018

           

 

Mr. Kaimin Bian

Chief Executive Officer

Hangzhou Karic Commodities Co., Ltd.

No. 2 Fifth Avenue

West Lake Science and Economic Zone

Hangzhou, Zhejiang, 310030

China

 

Dear Mr. Bian:

 

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Hangzhou Karic Commodities Co., Ltd., at No. 2 Fifth Avenue, West Lake Science and Economic Zone, Hangzhou, from March 26 to 29, 2018.

 

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 April 19, 2018, 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 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 released your over-the-counter (OTC) drug products, (b)(4) Lotion (active ingredient: (b)(4)), (b)(4) Cream (active ingredient: (b)(4)), and (b)(4) Cream (active ingredient: (b)(4)), without adequate testing for the identity and strength of active ingredients. Without this testing, you cannot determine if your drug products conform to specifications.

 

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 validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

 

Your firm failed to test incoming raw materials, including the active ingredients (b)(4) and (b)(4), and you also lacked testing of inactive ingredients such as (b)(4), for identity, purity, strength, and other appropriate quality attributes. Instead, your firm relied on certificates of analysis (COA) from suppliers without establishing the reliability of the suppliers’ analysis through appropriate validation.

 

3.      Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

 

You initiated an investigation on January 29, 2018, after you observed that the primary packaging (tube) of a reserve sample of (b)(4), lot (b)(4), had turned from (b)(4) (at the time of release) to yellow. Your investigation determined that your supplier sent the wrong material for primary packaging. You also failed to evaluate the effects of this deviation on the drug product within the container. In addition, you failed to determine whether other distributed batches of drug products may also have been affected by incorrect packaging material.

 

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)).

 

You have not validated the processes you use to manufacture drug products. For example, you did not conduct process performance qualification studies, and you lack 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.

 

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/guidances/ucm353925.pdf.

 

Overall Response

 

In your response, you acknowledged the signifigance of the CGMP observations; however, you provided limited corrective actions and did not provide sufficient detail and evidence to support that your proposed corrective actions will bring your operations and distributed drug products into compliance with CGMP. In your response you also stated that you are “a cosmetics manufacturer, [and you] . . . have no intention of making any drug products,” and that you will work with your client to upate your product labels.

 

As stated in this letter, the products you manufactured and distributed to the U.S. are considered drug products. Section 201(g)(1) of the FD&C Act defines drugs, in part, by their intended use, as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”

 

We strongly recommend engaging a consultant to assist your firm in meeting the applicable 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.

 

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 July 16, 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 Hangzhou Karic Commodities Co., Ltd., at No. 2 Fifth Avenue, West Lake Science and Economic Zone, 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:

 

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 3006528506.

 

 

Sincerely,

/S/ 

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

 

 

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(b)(4)