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FDA警告信22/03/18--无菌生产违反FDCA(中英文)

FDA、EU等对无菌生产的要求越来越严格,企业应遵守法律法规和行业标准安排生产。
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无菌生产违反联邦食品、药品和化妆品法案(FDCA),FDA发出警告信。
WARNING LETTER
Med Shop Total Care, Inc.
MARCS-CMS 628182 — MARCH 18, 2022
Dear Ms. Yoakum:
From July 7, 2021, to July 27, 2021, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Med Shop Total Care, Inc., located at 470 E Loop 281, Longview, TX 75605. During the inspection, the investigator noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
从2021年7月7日到2021年7月27日,美国食品和药物管理局(FDA)检查员检查了贵司位于德克萨斯州朗维尤市470e Loop 281, 75605的设施Med Shop Total Care, Inc.。检查中,调查员注意到贵司生产无菌药品时存在严重缺陷,这将患者面临风险。
FDA issued a Form FDA 483 to your firm on July 27, 2021. FDA acknowledges receipt of your facility’s response, dated August 17, 2021. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
FDA于2021年7月27日向贵公司出具了FDA 483表格。FDA确认收到贵工厂2021年8月17日的回复。根据这次检查,贵司生产的药品违反了联邦食品、药品和化妆品法案(FDCA)。
A. Compounded Drug Products Under the FDCA

A. FDCA下的合成药品

Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].
FDCA第503A条描述了由州许可药房或联邦机构的许可药剂师或许可医生配制的人用药品符合FDCA的三个部分豁免条件:符合当前良好生产规范(CGMP)(第501(a)(2)(B));标签有适当的使用说明(第502(f)(1)条);和FDA上市前批准(第505条)[21 U.S.C.§§351(a)(2)(B),352(f)(1)和355(a)]。
B. Violations of the FDCA

B、 违反FDCA

Adulterated Drug Products
掺假药品
The FDA investigator noted that drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigator observed:
FDA检查员观察到药品是在不卫生的条件下生产、包装或保存的,它们可能被污染或对健康造成损害,因此根据FDCA第501(a)(2)(a)条规定,贵司的药品为掺假药品。例如,检查员观察到:
1. You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO 5 aseptic processing area.
1. 在ISO 5无菌工艺区域内微生物污染恢复后,未对产品进行足够的评估并采取适当的纠正措施。
2. An operator placed their gloved hands outside the ISO 5 aseptic processing area to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood.
2. 操作人员将带手套的手放在ISO 5无菌处理区外,在重新进入ISO 5防护罩前没有对带手套的手进行消毒。
3. Your firm failed to establish an adequate contact time for a disinfecting agent used in your aseptic processing areas.
3.贵公司未能为无菌生产区域使用的消毒剂确定适当的接触时间。
4. A brownish residue on the protective screen of the HEPA filter within your ISO 5 aseptic processing area.
4. 在ISO 5无菌处理区域内的高效过滤器的保护屏上有棕色残留物。
It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.
根据FDCA (21 U.S.C.§331(k))第301(k)条规定,如果在州际商业运输后药品处于待售期间并导致药品被掺假,则禁止对药品采取任何行为。
C. Corrective Actions

C、 纠正措施

We have reviewed your firm’s response to the Form FDA 483.
我们已经审查了贵公司对FDA 483表格的回复。
Regarding your responses related to the insanitary conditions, some of your corrective actions appear adequate; however, the following corrective actions appear deficient:
关于对不卫生条件的回复,贵司的一些纠正措施似乎是充分的;但是,下列纠正措施似乎有缺陷:
1. Regarding your response to Observation 1, your response is inadequate. Any microbial contamination in the ISO 5 area is considered an insanitary condition. Any microbial contamination within the ISO 5 area is a serious concern and upon recovery, your firm should immediately assess the impact on drug products produced. This assessment should include a thorough evaluation of how contamination could have entered this critical area, and over what period of time the contamination could have existed, as well as drug products that remain on the market that could be affected.
1. 关于贵司对观察1的回复,是不充分的。ISO 5区域内的任何微生物污染都被认为是不卫生状况。ISO 5范围内的任何微生物污染都是严重问题,回收后,贵公司应立即评估对所生产药品的影响。该评估应包括全面评估污染是如何进入这一关键区域的,污染可能存在的时间,以及可能受到影响的仍在市场上的药品。
In addition, in response to Observation 7, we acknowledge your immediate recall upon notification from your third-party testing laboratory of a sterility failure for a bulk intermediate. We also acknowledge your statement that all recovered prescriptions that contained the lot in question “…were tested for sterility and test results showed that all were sterile.” Please note, microbial contamination, when present, is not uniformly distributed within a batch; therefore, it may not be identified in a sterility test. Compounding facilities producing drug products intended to be sterile under insanitary conditions should not rely upon or cite a passing sterility test result as an indication of product sterility.
另外,对于观察结果7,我们确认贵司在收到第三方检测实验室的散装中间体无菌失败通知后立即召回。我们也承认贵司的声明,即所有回收的含有问题批次的处方“……都经过了无菌测试,测试结果显示所有都是无菌的”。请注意,微生物污染,当存在时,不是均匀分布在一个批次;因此,它可能无法在无菌检验中被识别。在不卫生条件下生产无菌药品的生产设施不应依赖或引用通过的无菌试验结果作为产品无菌的指标。
2. In response to Observation 5, we acknowledge your statement, “In an effort to reduce movement in and out of the hood, we are currently testing computer keyboards that are designed for clean room areas, and which may be kept inside the hood, so that logging information can be conducted during our processing.” However, your response is inadequate as it does not indicate a timeframe for implementation or any appropriate interim actions to address this concern.
2. 针对观察报告5,我们承认贵司的声明:“为了减少进出防护罩的移动,我们目前正在测试为洁净室区域设计的电脑键盘,这些键盘可能会放在机罩内,以便在处理过程中记录信息。”然而,贵司的回复是不充分的,因为它没有指出实施的时间框架或任何适当的临时措施来解决这一问题。
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A.
请注意,无论贵司合成的药品是否符合第503A条的条件,FDCA第501(a)(2)(a)条关于卫生条件的规定也需要适用。
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug processing expertise should assist you in conducting this comprehensive evaluation.
FDA强烈建议贵司的管理层对运营进行全面评估,包括设施设计、程序、人员、工艺、维护、材料和系统。特别是,该审查应评估贵司的无菌工艺操作。具有相关无菌药品专业知识的第三方顾问应协助进行综合评估。
D. Conclusion

D、 结论

The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
在这封信中提到的违规行为并不是贵工厂违规行为的全面描述。贵司有责任调查和确定任何违规行为的原因,并防止其再次发生或其他违规行为的发生。也有责任确保贵公司遵守联邦法律的所有要求,包括FDA法规。
You should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.
应该立即采取行动纠正任何违规行为。如果未能充分解决任何违规行为,可能会在不另行通知的情况下导致法律行动,包括但不限于扣押和禁令。
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of any violations, as well as copies of related documentation. If you believe that your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.
在收到这封信后的十五(15)个工作日内,请以书面形式通知本办公室贵司为解决任何违规行为所采取的具体措施。请说明为防止任何违法行为再次发生而采取的每一措施,并附上相关文件的副本。如果认为贵司的产品没有违反FDCA,请提供理由和任何支持信息,以供我们考虑。如果不能在十五(15)个工作日内完全解决此问题,说明延迟的原因和完成时间。
Your written notification should refer to the Warning Letter Number above (Case #628182). Please electronically submit your signed reply on your firm’s letterhead to ORA PHARM2 Acting DCB at orapharm2actingdcb@fda.hhs.gov and orapharm2_responses@fda.hhs.gov.
If you have questions regarding the contents of this letter, you may contact Mr. Thao Ta, Compliance Officer, via phone at 214-253-5217 or e-mail at thao.ta@fda.hhs.gov.
Sincerely,
/S/
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
Division II
cc: VIA ELECTRONIC MAIL
Tim Tucker, Pharm.D., Executive Director/Secretary
Texas State Board of Pharmacy
333 Guadalupe, Suite #3-500
Austin, Texas 78701
tim.tucker@pharmacy.texas.gov
发布于 2022-07-22 11:20:24 © 著作权归作者所有
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