[FDA警告信]印度Resonance （320-17-23）

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Warning Letter 320-17-23

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Return Receipt Requested

February 3, 2017

Tushar B. Gore

Director

Resonance Laboratories Pvt. Ltd.

No. 8C & 9A, KIADB Industrial Area

Bashettihalli, Doddaballapur

Bangalore, India 561203

Dear Mr. Gore:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Resonance Laboratories Private Limited at No. 8C & 9A, KIADB Industrial Area, Bashettihalli, Doddaballapur, Bangalore, from May 2 to 6, 2016.

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 May 26, 2016, response in detail and acknowledge receipt of your subsequent correspondence.

Your, response was inadequate. Although you committed to addressing issues identified with the water systems and cleaning validation, your overall response lacked details. You also did not include a retrospective review of CGMP deficiencies on the quality of your products already distributed to the United States.

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

1.  Failure to validate that your water system is capable of consistently producing water suitable for its intended use.

1.  未能有效验证你们的水系统的持续生产符合预期用途的水的能力。

Your firm manufactures API that are used by your customers to produce sterile drug products.  You failed to demonstrate that distilled water used to clean equipment downstream of the (b)(4) purification steps is suitable for use. For example, the distilled water used for cleaning equipment in the (b)(4) cleanrooms, after passing through a (b)(4) micrometer filter, had an unacceptable level of bioburden.

贵公司生产的原料药是你们的客户用来生产无菌产品的。你们没有证明在某纯化步骤用来清洁设备的蒸馏水适用其用途。例如，蒸馏水用来清洁ZZ洁净间的设备，在通过YY微米过滤器过滤后，有不可接受的生物负荷。

2. Failure to have adequate cleaning procedures to prevent contamination or carry-over of a material that would alter the quality of the API.

2. 没有足够的清洁程序来避免会改变原料药质量的物料的交叉污染或残留。

Your firm uses shared equipment for the API you manufacture. Data from cleaning verification and validation studies found that your cleaning procedures were ineffective. For example, our investigator discovered that 105 of (b)(4) cleaning verification samples taken between 2015 and the start of our 2016 inspection failed your firm’s specification of no more than (b)(4) ppm for residual drug. After obtaining failing cleaning verification results, you repeated cleaning until you obtained passing verification results. Your firm failed to investigate recurring cleaning procedure ineffectiveness and did not remediate the deficient procedures.

贵公司使用了共用设备来生产原料药。从清洁确认和验证研究中的数据发现你们的清洁程序是无效的。例如，我们的检查员发现105个从2015年到2016年我们开始检查取的XX清洁确认样品不符合你们公司的残留药品XX4ppm的标准。在得到失败的清洁确认结果后，你们反复清洁直到你们得到合格确认结果。贵公司没有调查重复进行的清洁程序的无效性并没有修订你们有缺陷的程序。

CGMP consultant recommended

Based upon the nature of the deviations 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.

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 violations.

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 drugshortages@fda.hhs.gov, 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 Resonance Laboratories Private Limited at No. 8C & 9A, KIADB Industrial Area, Bashettihalli, Doddaballapur, Bangalore, 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 [url=]CDER-OC-OMQ-Communications@fda.hhs.gov[/url] or mail your reply to:

Rokhsana Safaai-Jazi

Compliance 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 3004483648.

Sincerely,

/S/

Thomas Cosgrove

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

zysx01234

清洁验证不合格还说了卵啊，应该分析原因或修改清洁方法并重新安排验证。

静水蓝心

阿三有一套