Fercy Personal Care Products Co., Ltd 9/7/12
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Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Center for Tobacco Products
9200 Corporate Boulevard
Rockville, MD 20850-3229
VIA UPS MAIL
September 7, 2012
Mr. Shi Xiaojun
Owner and General Manager
Fercy Personal Care Products Co., Ltd
An’Wen Industrial Zone, PanAn County
Jinhua, Zhejiang 322300
Dear Mr. Xiaojun:
During our March 5-6, 2012 inspection of your pharmaceutical manufacturing facility, Fercy Personal Care Products Co., Ltd., located at An’Wen Industrial Zone, PanAn County, Jinhua, Zhejiang, 322300 China, an investigator from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product, (b)(4), to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
Specific violations observed during the inspection include, but are not limited to, the following:
1. Your quality control unit failed to exercise its authority to approve or reject drug product components, containers, closures, in-process materials, packaging material, labeling and finished products. Secondly, the quality control unit failed to approve procedures and specifications impacting the identity, strength, quality and purity of the drug product. Finally, there are no written procedures describing the responsibilities and procedures applicable to the quality unit [21 C.F.R. § 211.22].
Three examples of violations of § 211.22 are as follows:
a. The raw materials and components used in the production of the drug product were not approved by the quality unit.
b. The quality unit failed to approve procedures and specifications impacting the quality of the (b)(4).
c. There are no written procedures describing the Quality Unit responsibilities.
Additionally, records pertaining to the production and release of your drug products were not provided to the investigator for review. The only documentation available on site for the batches of drug products manufactured by your firm was two pages from a notebook listing the ingredients used.
In your response to this letter, please provide information defining the roles and responsibilities of your quality unit. Also, include the written procedures developed and applicable to your Quality Unit. Explain how you will assure that your Quality Unit is exercising its responsibility related to the quality of the product produced and released from your facility.
2. Your firm failed to provide adequate written production and control procedures which are designed to assure that the drug products produced have the identity, strength, quality and purity they purport or are represented to possess [21 C.F.R. § 211.101].
For example, there are no written production and control procedures to ensure the batches are formulated to provide not less than 100 percent of the labeled or established amount of active ingredient. Additionally, there are no written production and control procedures specifying that the components added to each batch should be verified by a second person.
In your response to this letter, provide copies of your production and control procedures for the manufacture of all drugs produced at your facility, including supporting validation documents. Also, include a copy of your Master Batch record for the different products intended for the U.S. market.
3. 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 C.F.R. § 211.165(a)].
To date, your firm has not conducted release testing on any batches of drug product distributed to the U.S. market. Specifically, the identity and strength of the active ingredient, (b)(4), was not determined for your (b)(4) product. Your firm also failed to perform tests for the (b)(4) and (b)(4).
Your response to this letter should include a commitment to test all products according to appropriate finished product release specifications.
4. Your firm does not have a written testing program designed to assess the stability characteristics of drug products in order to determine appropriate storage conditions and expiration dates [21 C.F.R. § 211.166(a)].
For example, your firm has no stability program for your drug product. Your firm’s labeling for (b)(4)(no lot number) provided during the inspection includes an expiration date of (b)(4). However, you have no data available to support this expiration date.
In your response to this letter, provide documentation to support the current expiration dates assigned to your drug products currently in U.S. distribution, as well as a commitment to ensure that each of your drug product types is routinely tested according to a stability program that has been approved by your quality unit. For any ongoing stability studies, provide detailed information about the program and a copy of your stability protocol. Please include the following: products, lot numbers, date the stability study started, stability interval, tests performed, storage conditions (temperature and humidity requirements), testing site, and assurance that your analytical methods are stability-indicating and appropriately validated (or, in the case of compendial methods, verified for their intended use).
5. Your firm did not appropriately sample, test, or examine the components, containers or closures used in the manufacture of the drug product [21 C.F.R. § 211.84].
Your firm manufactured drug products without examining or testing the components, containers and closures used for their manufacture. These items were used without being released by your quality unit for use.
Your response should include a detailed plan for the receipt, sampling, testing, and release or rejection of drug components, containers, and closures. Include a description of each test method to be employed and a demonstration that each analytical method is adequate for its intended use. For any components for which suppliers’ certificates of analyses (COA) will be used in determining adequacy, include a detailed plan for establishing the reliability of the supplier’s analyses, including frequency of COA verification testing. Note that at least one identity test shall be conducted for each lot of components used, and that COAs are not an acceptable substitution.
DRUG REGISTRATION VIOLATIONS
Your firm failed to fulfill its registration obligations under Section 510(i)(1) of the Act and its listing obligations under Sections 510(i)(2) and 510(j), which is prohibited under Section 301(p). 21 U.S.C. 360(i)(1) and (2), 360(j), and 331(p)
For example, in 2012, your firm offered for import into the United States drugs that you manufactured or otherwise processed at the above-referenced establishment. During that same time period, however, your firm did not maintain a current establishment registration and complete and accurate drug product listing with the FDA.
Please note that a drug offered for import into the United States may be refused admission under Section 801(o) of the Act if the importer, owner, or consignee is not able to provide a statement of the registration of the establishment that manufactured it. In addition, if a drug is not listed in accordance with Section 510 of the Act, including if the listing for the drug references a manufacturing establishment that does not maintain a current establishment registration, the drug appears to be misbranded under Section 502(o) and subject to refusal of admission under Section 801(a)(3). 21 U.S.C. 352(o)
FDA investigator(s) discussed this issue with you during the inspection. Information on how to register and list is available at the following internet website: http://www.fda.gov/cder/drls/registration_listing.htm. If you continue to produce drugs that are offered for import into the United States, you must complete the required registration and listing. You should provide evidence that you have fulfilled these requirements in your response to this letter.
Your firm terminated the US FDA inspection on March 6, 2012, prior to the investigator’s determination that the inspection was ready to be concluded and prior to the previously agreed upon conclusion date of March 9, 2012. Your decision to terminate the inspection prevented the FDA Investigator from reviewing relevant records related to the production, testing and holding of drug products intended for the US market, not being readily available for inspection.
During the inspection, your firm did not provide documentation identifying all batches of drug products distributed to the U.S. to date. Additionally, your firm did not provide the investigator with the name(s) and contact information of the regulatory agent, importer, broker and/or commercial agent. Finally, your firm did not provide the investigator with the contact information for the supplier of the containers and closures used in the manufacture of the drug products.
These unreasonable delays or denials in permitting FDA to access manufacturing conditions at your facility give the appearance that your products do not meet U.S. regulations and standards. We also note that prior to the inspection, you asked to cancel this inspection. In your response to this letter, please provide the distribution documentation for all batches of drug product manufactured at your facility distributed to the U.S., a list of all components used in the drug product, and the names of the components’ suppliers. In addition, provide your rationale for your premature termination of the inspection. Until you grant FDA on site access to all records required under this regulation, FDA will continue to consider your site unacceptable and your firm will remain on import alert.
Over-the-counter (OTC) drugs intended for distribution in the U.S., including OTC healthcare antiseptic products, need to be properly labeled. If the labeling does not include “Drug Facts,” then the products are misbranded. Specifically, should the OTC healthcare antiseptic products, (b)(4), and (b)(4), be intended for distribution in the U.S., their labeling must comply with all of the requirements of section 502 of the Act and all pertinent regulations found in Title 21 of the Code of Federal Regulations (21 CFR) particularly, 21 CFR 201.66 which calls for the inclusion of the Drug Facts labeling for OTC drug products.
In addition, OTC healthcare antiseptics for over-the-counter human use are being evaluated under FDA's OTC Drug Review. Tentative Final Monographs (TFM) for such products were published in the Federal Register of 59 FR 31402 (June 17, 1994) and 56 FR 336444 (July 22, 1991). Pending the implementation of a final monograph, we do not object to the marketing of topical OTC antimicrobial products that meet the formulation and labeling described in such TFMs. Such marketing is subject to the risk that it may be necessary to reformulate and/or relabel such products or seek FDA approval through the NDA procedures of the Act [section 505] once a final monograph is in effect.
In addition to the items listed above, the investigator found many other deficiencies that lead us to question the effectiveness of your current quality system to achieve overall compliance with CGMP at your facility. We recommend that you seek the advice of a third-party consultant for assistance with a complete evaluation to determine the improvements that you will need to make at your firm in order to meet the CGMP requirements for the manufacture of OTC drug products.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. It is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations.
Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. Because your firm is currently under Import Alert, the drugs you ship are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)], in that the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)]. Until such time as your manufacturing practices are verified to comply with CGMP, your firm will remain under FDA Import Alert, and FDA will continue to refuse admission of articles manufactured at Fercy Personal Care Products Co., Ltd., An’Wen Industrial Zone PanAn County, Jinhua, Zhejiang, China, into the United States.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute the drug product(s) manufactured at this facility and provide the date and reason you ceased production. Please identify your response with FEI # 3008254880.
If you have questions or concerns regarding this letter, contact Allison A. Aldridge, Ph.D., Compliance Officer, at the below address and telephone number.
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Office of Manufacturing and Product Quality
Division of International Drug Quality
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-0483
Fax: (301) 847-8741
Office of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research