- Foshan Flying Medical Products Co., Ltd.
- Issuing Office:
- Center for Drug Evaluation and Research
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10903 New Hampshire Avenue
Silver Spring, MD 20993
Via UPS Warning Letter 320-17-43
August 1, 2017
Ms. Yue Mei Liang
Foshan Flying Medical Products Co., Ltd.
Zumiao 1st Road, Chancheng
Xiaofengtian Industrial District, Wuzhuang, Luocun Town
Foshan City, Guangdong Province 528000
Dear Ms. Liang:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Foshan Flying Medical Products Co., Ltd. at Zumiao 1st Road, Chancheng, Xiaofengtian Industrial District, Wuzhuang, Luocun Town, Foshan City, Guangdong Province from February 20–23, 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 March 29, 2017, response in detail, and acknowledge receipt of your subsequent response.
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 and procedures applicable to the 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) and (d)).
Your firm lacks an adequate quality control unit.
You failed to establish written procedures for numerous functions. For example, there were no procedures addressing the quality control unit, complaints, deviations, investigations, and various other basic drug manufacturing operations.
Further, your quality unit lacked documentation to demonstrate acceptability of batch manufacturing and quality. For instance, you lacked records relating to:
- change control;
- annual product reviews;
- batch record review to assure that any errors were fully investigated; and
- approval or rejection of your drug products.
In addition, for the past three years, your quality unit consisted of (b)(4) employee from the production department, whose responsibilities included recording information in batch records during operations.
In response to this letter, provide your corrective actionsto ensure that:
- you establish an adequate quality control unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality;
- you establish adequate procedures in accord with CGMP covering all aspects of your facility and operations that may compromise the identity, strength, quality, and purity of your drug products; and
- you create and maintain full documentation to demonstrate acceptability of all operations.
2. 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 conduct appropriate laboratory testing for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(a) and (b)).
You released finished drug products without adequate acceptance testing. For example, you did not test your (b)(4) and (b)(4) to determine if they conformed to the identity or strength stated on the label. In addition, you did not adequately test for critical microbial attributes (e.g., absence of objectionable microorganisms, total count).
In response to this letter, describe your corrective action plan to ensure that you test all drug product batches before you release or reject them. Your release testing program should include written procedures describing your testing requirements for each product, as well as validated test methods with appropriate acceptance criteria.
3. Your firm failed to have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).
You market an (b)(4) product labeled as “sterile.” The label states that the product is used “(b)(4).” However, you failed to perform sterility testing. It is essential that you conduct sterility testing on these and other purportedly sterile drugs prior to batch disposition decisions.
In response to this letter, describe your corrective action plan to ensure that all batches intended to be sterile are tested for sterility by an appropriate laboratory method as part of release testing. Include your batch release procedures and test methods.
4. Your firm failed to establish 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 lacks 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 approaches that FDA considers appropriate elements of process validation, at http://www.fda.gov/downloads/Drugs/.../Guidances/UCM070336.pdf
In response to this letter, detail your validation plan for ensuring an ongoing state of control. Include a timeline for performing process performance qualification (PPQ) for each of your drug products, and describe your approach for monitoring batch-to-batch variation on an ongoing basis.
5. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced, and to maintain such records for at least one year after the expiration of the batch (21 CFR 211.188 and 211.180(a)).
During the inspection, our investigator asked to review batch records for your products. Your employee was only able to provide a single recent batch record for (b)(4) your (b)(4) products. When our investigator asked to see your other batch records, your staff stated that there were no other records. Your firm’s senior management stated that batch records are only retained for approximately six months after production. You are required to maintain records associated with a batch of drug product for at least one year after the expiration date of the batch.
Your batch record also lacked sufficient information necessary to determine whether your products were manufactured properly. For instance, your batch records lacked:
- batch numbers for raw materials used in the manufacturing process; and
- information on equipment and methods used to (b)(4) active ingredients (e.g., (b)(4); (b)(4)).
In response to this letter, provide your:
- revised master records for each of your drug products that fully document the manufacturing operation, including one executed batch production and control record for each product; and
- remediated record retention policy setting forth acceptable retention periods.
6. Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a)).
Your firm was unable to provide any CGMP-related training documentation. Your firm’s senior management further stated that no CGMP-related training has ever been provided to employees.
In response to this letter, provide details of your proposed training program to ensure that each person is equipped to effectively perform his or her assigned functions. Include provisions for an ongoing training program for all staff who conduct or supervise CGMP functions. Also include individual training records demonstrating that employees are qualified to perform their functions.
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 firm’s executive management remains responsible for fully resolving all deficiencies and for 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.
If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at firstname.lastname@example.org
, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b) and allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.
FDA placed your firm on Import Alert 66-40 on May 23, 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 Foshan Flying Medical Products Co., Ltd., Zumiao 1st Road, Chancheng, Xiaofengtian Industrial District, Wuzhuang, Luocun Town, Foshan City, Guangdong Province, 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.
Lixin (Leo) Xu, M.D., Ph.D.
U.S. Food and Drug Administration
White Oak Building 51, Room 4212
10903 New Hampshire Avenue
Silver Spring, MD 20993
Please identify your response with FEI 3009206013.
Thomas J. Cosgrove, J.D.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research