Recipient NameMr. Ma Xing Fa
Recipient TitleGeneral Manager
- Hangzhou SunKing Nonwovens Co., Ltd.
No. 888 Chongchao Rd., Chongxian Industrial Area
- Issuing Office:
- Center for Drug Evaluation and Research
Via UPS Warning Letter 320-19-10
Return Receipt Requested
January 29, 2019
Mr. Ma Xing Fa
Hangzhou Sunking Nonwovens Co., Ltd.
No. 888 Chongchao Rd., Chongxian Industrial Area
Hangzhou, Zhejiang, 311108 China
Dear Mr. Ma:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility Hangzhou Sunking Nonwovens Co., Ltd., at No. 888 Chongchao Rd., Chongxian Industrial Area, Hangzhou, Zhejiang, from August 7 to 9, 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 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 response, received on September 24, 2018, in detail.
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 over-the-counter (OTC) (b)(4) drug products without appropriate quality control release testing, including but not limited to, the identity testing of (b)(4) active ingredient.
In addition, we have concerns about the validity of test results for your finished drug product. Reports from your contract laboratory included strength test results of (b)(4) active ingredient and microbial test results (total bacterial and total fungal counts) that were identical for (b)(4) batches of your (b)(4) drug product that were shipped for distribution to the U.S. market.
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 lacked testing of incoming raw materials, used in the manufacturing of your drug product, including active pharmaceutical ingredients and other components, for their identity, strength, and other quality attributes. Your firm also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of the suppliers’ analyses through appropriate validation.
3. Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
Your firm has not established a stability program, including written procedures. Your firm also did not have stability data to support the (b)(4) expiration dates assigned to your OTC drug product. Without stability data, you cannot assure the quality of your drug products throughout their labeled shelf lives.
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 has not validated the processes used to manufacture your drug products. Your firm did not perform process qualification studies and 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 general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf.
5. 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)).
Your firm lacks an adequate quality unit. You have not established written procedures for numerous functions of the quality unit, including but not limited to, quality unit operations, batch release, change control, complaints, supplier qualification, recalls, and annual product reviews. During the inspection, you indicated that your firm lacks a quality agreement describing the roles, responsibilities, and procedures to be followed by you and your contract laboratory regarding component and final product testing.
Use of Contract Laboratories
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. As such, you are responsible for making final release decisions.
You are responsible for the quality of drugs you produce, regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure 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.
Quality Systems Guidance
Your firm’s quality systems are inadequate. For guidance on establishing and following CGMP compliant quality systems, see FDA’s guidance’s: Q8(R2) Pharmaceutical Development, at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; Q9 Quality Risk Management, at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; and Q10 Pharmaceutical Quality System, at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Your response to the FDA inspection did not provide sufficient details or evidence that your firm will remediate your operations to ensure compliance with CGMP.
In response to this letter, provide the following:
• The test methods and specifications you use to analyze each batch of drug product prior to release, including both chemical and microbial quality attributes. Include a summary of all test results obtained from testing of all batches of drug products intended for the U.S. market within expiry. Include your procedures that will ensure you test each batch of finished drug product, prior to release, according to batch release specifications.
• Your plan for testing retains of all drug products distributed to the U.S. market within expiry for identity and strength of active ingredients, and microbial quality, including total count and objectionable microorganisms. If you released any batch that were out of specification (OOS), indicate the corrective actions you will take, such as customer notifications and product recalls.
• Batch release specifications for all incoming components including the (b)(4). Include your procedures for analyzing each batch of incoming components and the procedure that requires testing of components prior to release and use.
• Provide a risk assessment of all drug products distributed to the U.S. market within expiry, to determine the impact of not testing components, such as the (b)(4).
• Your plan, with timelines, to develop and implement a complete drug stability program. This plan should include an assessment of stability by testing retain samples of your drug product in the U.S. market within expiry. Indicate the corrective actions you will take, including notifying customers, if OOS results are found.
• A risk assessment of the drug products distributed to the U.S. market within expiry that were not supported by adequate stability testing.
• Process performance qualification for your drug products. Provide a detailed summary of your approach for routinely monitoring intra-batch and inter-batch variation.
• Your corrective and preventive action (CAPA) plan for establishing an effective quality control unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. Include newly established and updated procedures.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, if your firm resumes manufacturing drugs for the United States market, 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.
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 your facility.
FDA placed your firm on Import Alert 66-40 on December 13, 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 Sunking Nonwovens Co., Ltd., No. 888 Chongchao Rd., Chongxian Industrial Area, Hangzhou, Zhejiang 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:
Cesar E. Matto
Senior Policy Advisor
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 3010166722.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research