- Delivery Method:
- VIA UPS
Recipient NameMr. Huaijun Yin
- Yino, Inc.
2 Cuiping Erxiang
Chongqing Shi, 401120
- Issuing Office:
- Center for Drug Evaluation and Research
10903 New Hampshire Avenue
Silver Spring, MD 20993
October 28, 2019
Warning Letter 320-19-35
Dear Mr. Yin:
The U.S. Food and Drug Administration (FDA) inspected your facility, Yino Inc. at 2 Cuiping Erxiang, Yubei District, Chongqing, from March 18 to 22, 2019.
This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your API 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 12, 2019, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific deviations including, but not limited to, the following.
1. Failure to transfer all quality or regulatory information received from the API manufacturer to your customers.
You re-label active pharmaceutical ingredients (API) manufactured by other manufacturers and distribute the API to other facilities. API distributed by your firm was imported into the United States. For API you re-labeled, you omitted the name and address of the original manufacturer on certificates of analysis (COA) you generated with your company letterhead. For example, you omitted the manufacturer information for (b)(4) on the COA for several lots of (b)(4) API. (b)(4) API is used in injectable-grade drugs supplied to compounding pharmacies and intended for (b)(4) treatment.
Regulators and customers rely on COA to provide accurate information about the quality and source of drugs and their components. Omitting information on a COA compromises supply chain accountability and traceability and may put consumers at risk.
See our Guidance for Industry ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients for more information on how API from original manufacturers as well as API re-packagers and re-labelers should be labeled to clearly identify the original API manufacturer as the API moves through the supply chain. The guidance can be found at the following website: https://www.fda.gov/media/71518/download.
We acknowledge that your response provided new procedures to ensure required information will be provided on the COA you generate in the future. The implementation and effectiveness of these procedures will be evaluated in a future inspection. Your response is inadequate as your retrospective review only covered a limited period of 15 months. However, the (b)(4) API you distributed notably has a (b)(4) expiration date.
In response to this letter, provide:
• A retrospective review to determine how your failure to provide required information may have affected drug quality. Ensure that your review goes back at least three years to fully cover the expiry or retest period for any API or intermediate that has been distributed by your firm.
• Any actions you have taken or will take, such as notifying customers, recalling drugs, or invalidating previously issued COA for any drugs still within their labeled retest dates
2. Failure to establish, document, and implement an effective system to manage quality.
Your firm failed to establish an adequate quality system and lacks quality oversight on documentation. For example, COA created and issued by your firm for several lots of (b)(4) API distributed to the U.S. market lacked signatures and dates from an authorized person in the Quality Unit. You included a test parameter and result that was not performed by the original API manufacturer, nor could you provide evidence that you had performed the test. Additionally, your firm lacked written procedures for re-labeling operations, drug release, document retention, and document control.
Failing to establish and implement a robust quality system, including an adequate organizational structure, at your firm compromises the assurance that the released API meet required specifications of quality and purity.
We acknowledge that your response provided new procedures to prevent similar errors from occurring. However, these procedures themselves do not demonstrate a robust quality system.
In response to this letter, provide a plan to establish, document, and implement an effective system for managing quality.
See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems, and for risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211. The guidance can be found at the following website: https://www.fda.gov/media/71023/download.
CGMP Consultant Recommended
Based upon the nature of the deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations 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 resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
Deviations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these deviations, for determining the causes, for preventing their recurrence, and for preventing other deviations in all your facilities.
FDA placed your firm on Import Alert 66-40 on August 1, 2019.
Until you correct all deviations 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 deviations may also result in the FDA continuing to refuse admission of articles manufactured at Yino Inc., 2 Cuiping Erxiang, Yubei District, Chongqing, 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 deviations 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 M.S.
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 3015238172.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research