- Yangzhou Hengyuan Daily Chemical Plastic Co Ltd
- Issuing Office:
- Center for Drug Evaluation and Research
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Avenue|
Silver Spring, MD 20993
Warning Letter 320-16-34
Return Receipt Requested
September 26, 2016
Mr. Yan Qunfeng
Yangzhou Hengyuan Daily Chemical Plastic Co., Ltd.
No. 1 Sitong Road
Hanji Industrial Park
Yangzhou, Jiangsu 225111
Dear Mr. Yan:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou Hengyuan Daily Chemical Plastic Co., Ltd., at No. 1 Sitong Road, Hanji Industrial Park, Yangzhou, Jiangsu, from January 18 to 22, 2016.
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 firm’s January 30, 2016, response in detail.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. 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 CFR 211.101).
FDA collected samples of your (b)(4) batch #(b)(4) at the port of entry. FDA Laboratory analysis found that your (b)(4) did not contain any of the labeled active ingredient, (b)(4). FDA denied entry of the shipment accordingly and notified your customer, (b)(4), which filed a complaint with you.
Your subsequent investigation into the customer complaint for batch #(b)(4) revealed that, during (b)(4) of components, you added the wrong ingredient, (b)(4), instead of the active ingredient.
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)).
During the inspection, you acknowledged that your firm did not test all batches of finished drug product prior to release. For example, in 2015 you tested only five of the (b)(4) batches shipped to the United States. We note you did not perform the active ingredient assay for batch #(b)(4) prior to release. FDA analysis showed this batch contained no active ingredient.
Your quality unit must review all production and control records, and ensure testing and conformance to all product specifications, prior to permitting release of a batch to the United States market. We acknowledge that you committed to test drug product batches for U.S. distribution in the future.
Your investigation indicated the warehouse released the wrong active ingredient for batch #(b)(4). This was the first of multiple errors that led to adding the wrong ingredient to your drug product.
In response to this letter, provide an action plan to comprehensively evaluate your manufacturing operation to determine the root causes for these errors, and to prevent use of the wrong ingredient or other hazardous mix-ups for all of your drug products. Additionally, provide the revised master batch record for (b)(4). Describe all improvements to batch records, including addition of verifications for all critical manufacturing steps.
Describe your corrective actions and preventive actions (CAPA) to ensure that your finished drug products meet their specifications. Evaluate previous batches distributed in the United States within expiry to determine if they meet specification. As part of your CAPA plan, describe how your quality unit authorities and responsibilities will be enhanced to ensure ongoing oversight over your drug manufacturing operations. Also describe how you plan to measure the effectiveness of your CAPA and a timeline for completion of these actions.
CGMP consultant recommended
Based on 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 obligation to comply with CGMP. Your 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 August 12, 2016.
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 Yangzhou Hengyuan Daily Chemical Plastic Co., Ltd., No. 1 Sitong Road, Hanji Industrial Park, Yangzhou, Jiangsu, 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.
Runa Musib, Compliance 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 3008519597.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research