FDA警告信:臺灣CHENG FONG(節譯)

翻譯：Julia朱玉姣 來自：蒲公英

Warning Letter 320-16-33

Via UPS                                                                                 

Return Receipt Requested

 September 15, 2016

  Mr. Hung Chih Wu

General Manager

Cheng Fong Chemical Co. Ltd.

No. 19, Gong 4th Road

Dayuan District                                                         

Taoyuan City 337, Taiwan

 

Dear Mr. Wu:

 The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Cheng Fong Chemical Co. Ltd., at No. 19, Gong 4th Road, Dayuan District, Taoyuan City from April 18 to 22, 2016.

美國FDA於2016年4月18-22日檢查了你們臺灣桃源的工廠。

This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).

 此警告信總結了你們原料藥生產中違背CGMP的重大偏差。

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).

鑑於你們生產、加工、包裝和存貯所用方法、設施或控制不符合CGMP，你們的原料藥根據法規屬於摻假藥品。

We reviewed your May 13, 2016, response in detail and acknowledge receipt of your subsequent correspondence.

 我們審核了你們公司於2016年5月13日及之後提交的回覆。

During our inspection, our investigator observed specific deviations including, but not limited to, the following.

檢查期間，我們調查人員發現了缺陷具體包括但不僅限於以下：

1.    Failure to have an adequate maintenance procedure to prevent contamination or carry-over of a material that would alter the quality of the API. 

 沒有足夠的維護程序來防止會改變原料藥質量的汙染和物料殘留。

Our investigator observed corrosion, pitting, dirt, and leaks, on and around your drug manufacturing equipment.

 我們調查人員發現你們的藥品生產設備上面和周圍有鏽蝕、凹痕、汙垢和洩漏。

For example, we observed pitting on the product contact surface of equipment (b)(4)-201, (b)(4)-202, and (b)(4)-203 used to process (b)(4) API.  

例如，我們發現在某原料藥工藝中與產品接觸的某設備表面有鏽蝕。

In your response, you provide updated equipment line clearance and maintenance procedures, photos of cleaned or repaired equipment, and a list of batches potentially impacted by the poorly maintained equipment.  

 在你們的回覆中，你們提供了更新過的設備線清場和維護程序，清潔後和維修後設備的照片，以及受到維護不良設備潛在影響的批次清單。

2.    Failure to adequately conduct investigations and extend the investigations to other batches that may have been associated with the failure or deviation.

 未能充分實施調查，並將調查延伸到可能與失敗或偏差相關的其它批次。

You did not adequately investigate customer complaints for black or (b)(4) foreign particles in your finished (b)(4).

 你們對某產品的黑色和異物顆粒客戶投訴沒有進行充分調查。

For example, you received particulate complaints for (b)(4) batch (b)(4), but rather than evaluating reserve samples for that batch, you evaluated a different batch of (b)(4) API (batch number (b)(4)). You found that batch (b)(4) contained foreign matter, yet you did not determine the identity of the foreign particulates in either batch or implement adequate corrective action.

 例如，你們收到某批號的一個顆粒物投訴，但你們沒有評估該批號的留樣，你們評估了某原料藥（批號為XX）另一個批號。你們發現該批號有一些異物，你們沒有鑑別出該批產品中的異物顆粒，也沒有實施充分的整改措施。

Your response acknowledged that the foreign particle complaints are likely due to the poor condition of manufacturing equipment. 

 你們的回覆說異物顆粒投訴可能是因為生產設備狀態不好引起的。

Your investigations into poor equipment maintenance and foreign particles are inadequate as you did not identify the foreign matter in your API, or sufficiently extend the investigations to other lots that may have been contaminated. Regarding the latter, reserve samples of all potentially-affected batches were not examined for presence of foreign matter.

你們對設備維護不良和異物顆粒的調查是不充分的，你們沒有鑑別出你們原料藥中的異物，也沒有將調查充分延伸到其它可能受到汙染的批次。關於後者，你們沒有對所有可能受影響批次的留樣檢查其異物。

3.    Failure to properly maintain buildings used in the manufacture of API in a clean condition.

 沒能適當維護原料藥生產用建築使其處於清潔狀態。

For example, our investigator observed filth, insects, wet layers of (b)(4) unidentified material on the floors, and foul odors in the cold rooms used to store raw materials and intermediates used in the manufacture of your finished API. Firm officials noted that the rooms had never been cleaned.

 例如，我們的調查人員在地板上發現汙垢、昆蟲、溼的不明物體，在用於存貯原料藥生產用原料和中間體的低溫房聞到惡臭味。公司管理人員注意到這些房間從來都沒被清潔過。

We acknowledge your corrective actions, including cleaning, and adding the cold rooms to your pest control program.

 我們已知你們的整改措施，包括清潔低溫間，以及將低溫間納入蟲鼠控制計劃。

In your response to this letter, provide the following:

在你們對此函的回覆中，請提供以下：

An updated and comprehensive investigation into your customer complaints

對你們客戶投訴更新後的全面調查

A corrective act

ion and preventive act

ion (CAPA) plan that includes identification of the foreign particles, your assessment of root cause, the impact on other potentially affected batches, and actions taken to prevent recurrence

一份CAPA計劃，包括對異物顆粒的鑑別，你們對根本原因的評估，其對其它潛在受影響批次的影響，防止其再次發生的措施

Updated and comprehensive assessment of the state of maintenance of all equipment that can be used in the manufacture of APIs for US supply

對可能用於供美國市場的原料藥生產的所有設備的維護狀態進行最新的全面評估

A comprehensive assessment of the adequacy of your maintenance program

對你們維護計劃的充分性進行全面評估

An evaluation of the adequacy of your cleaning procedures

對你們清潔程序的充分性進行評估

Conclusion

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 from CGMP.

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 [e-mail], 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.     

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 FDA refusing admission of articles manufactured at Cheng Fong Chemical Co. Ltd., No. 19, Gong 4th Road, Taoyuan City 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 [e-mail] or mail your reply to:

Marisa Heayn, Consumer Safety Officer

U.S. Food and Drug Administration

White Oak Building 51, Room 4359

10903 New Hampshire Avenue

Silver Spring, MD 20993

USA 

Please identify your response with FEI 1000174711. 

Sincerely,

/S/ 

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research