FDA警告信：英国McCallum Manufacturing Ltd. 20180409

Warning Letter 320-18-45

April 9, 2018

Mr. Iain McCallum, Owner

McCallum Manufacturing Ltd.

6A-D, Redbrook Business Park, Withorpe Road, Barnsley,South Yorkshire, S75 1JN United Kingdom

Dear Mr. McCallum:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, McCallum Manufacturing Ltd., at 6A-D,Redbrook Business Park, Withorpe Road, Barnsley, South Yorkshire, from July 24to 26, 2017.

美国 FDA 于 2017 年 7 月 24 日 26 日检查了你们位于英国南约克郡的 McCallumManufacturing Ltd. 生产场所。

This warning letter summarizes significant violationsof current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.

本警告信总结了制剂生产严重违反 CGMP 的行为。参见 21CFR 第 210 和 211 部分。

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).

由于你们的制剂生产、加工、包装或保存的方法、场所或控制不符合 CGMP 要求，你们的制剂根据 FDCA 的 501(a)(2)(B) 以及 21U.S.C. 351(a)(2)(B) 被认为是掺假药品。

We reviewed your August 15, 2017, response in detail.

我们详细审核了你们 2017 年 8 月 15 的回复。

During our inspection, our investigators observed specific violations including, but not limited to, the following.

检查期间，我们的调查人员发现的具体问题包括但不仅限于以下：

1.      Your firm failed tohave, 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)).   你公司未能在放行对每批药品进行适当的化验室检测，确定其是否符合药品最终质量标准，包括每种活性鉴别和剂量，以及对不得检出致病菌的每批药品在必要时进行适当的化验室检测 (21 CFR 211.165(a) and (b)) 。

You released your over-the-counter (OTC) drug product, (b)(4), without adequate testing for conformance to specifications,including identity and strength. You lacked testing procedures, specifications,and analytical data to support the release of your drug product.

你们放行了 OTC 药品 XX 却未执行充分的检测以确认其符合质量标准，包括鉴别和含量。你们缺少检测程序、质量标准和分析数据来支持对你们药品的放行。

In your response, you stated that you now have writtenstandard operating procedures (SOPs) for, among other things, “testing finishedproducts,” but you did not provide copies of any of these SOPs or thespecifications you or your contract testing laboratories are using to releaseyour drugs.

在你们的回复中，你们声称你们现在有了书面 SOP ，包括“成品检测”，但并未提交这些 SOP 的副本或你们或你们用于放行这些药品的合同检测化验室的标准。

In response to this letter, describe your correctiveaction plan and testing procedures to ensure that all drug product batches aretested for identity and strength prior to release for distribution to theUnited States. Your written procedures should describe your testingrequirements for your products, as well as validated test methods withappropriate acceptance criteria.

在回复此函时，请描述你们的纠正措施计划和检测方法以确保所有药品批次均在放行销售至美国之前检测其鉴别和含量。你们的书面程序应描述你们药品的检测要求以及经过验证的检测方法连同恰当的可接受标准。

2.      Your firm failed totest samples of each component for identity and conformity with all appropriatewritten specifications for purity, strength, and quality. Your firm also failedto establish the reliability of component supplier analyses on which you relyin lieu of certain tests through appropriate validation of the supplier’s testresults at appropriate intervals (21 CFR 211.84(d)(1) & (2)).   你公司未执行至少一项检测来确认药品的每种成分的鉴别。你公司说未通过对供应商检测结果以适当时间间隔进行验证的方式来建立组份供应商分析的可靠性却依赖于其结果替代某些检测 (21 CFR 211.84(d)(1) and (2)) 。  

You failed to test the incoming raw materials you useto manufacture your   (b)(4)  drug products to determine their identity,purity, strength, and other appropriate specifications.

你未能检测你们 XX 药品和平所用原料以确定其鉴别、纯度、剂量和其它适当的质量标准。

Instead, your firm used results from your suppliers’certificates of analysis (COA) without establishing the reliability of yoursuppliers’ analyses through appropriate validation, and without conducting atleast one specific identity test. You may not rely on your suppliers’ COA toverify the identity of your components.

你公司使用了供应商 COA 的结果，而未通过适当的验证建立你们供应商可靠性，亦未至少执行一项特定鉴别测试。你们不可依赖于供应商的 COA 来验证你们成分的鉴别。

In your response, you said that you identified allincoming materials used in the manufacture of the   (b)(4)productsagainst known standards. Your response was inadequate because you did notprovide procedures for testing incoming materials or results from any testing.In addition, you did not provide any information on how you will establish thereliability of your suppliers’ test results.

在你们回复中，你们说你们已识别出了 XX 药品生产所用的所有进厂物料，与已知标准进行比较。你们的回复是不充分的，因为你们并未提交进厂物料检测程序或任何检测的结果。另外，你们并未提交你们将如何建立你们供应商检测结果可靠性的任何信息。

In response to this letter, provide your procedure totest incoming components. Also, provide a detailed description of how you planto test each component for conformity with all appropriate writtenspecifications for identity, purity, strength, and quality. Explain how youintend to perform at least one identity test for all incoming components usedin your drug products. If you accept your suppliers’ COA in lieu of testingcomponents for purity, strength, and quality, specify how you plan to establishthe reliability of your suppliers’ test results through periodic validation.

在回复此函时，请提交你们进厂组份的检测程序，亦请提交一份详细的描述说明你们计划如何检测每种组份以确定其符合所有适当的书面鉴别、纯度、剂量和质量标准。请解释你们将如何对你们药品所用的所有进厂组份执行至少一项鉴别检测。如果你们接受供应商 COA 来取代对组份的纯度、剂量和质量的检测，请说明你们计划如何通过定期验证建立你们供应商检测结果的可靠性。

3.      Your firm failed toestablish a quality control unit with the responsibility and authority toapprove or reject all components, drug product containers, closures, in-processmaterials, packaging materials, labeling, and drug products. (21 CFR211.22(a)).   你公司未建立质量部门，具备职责和权力来批准或拒绝所有组分、药品容器、密闭器、中间体、包材、标签和成品 (21 CFR 211.22(a)) 。

Your firm lacked a quality control unit. You lackedwritten procedures for many quality unit operations, such as CGMP training,change control, annual product reviews, complaint handling, and oversight ofvarious other basic drug manufacturing and testing operations.

你公司缺少质量部门。你们缺少许多质量部门运作的书面程序，例如， CGMP 培训、变更控制、年度产品回顾、投诉处理和其它不同基本药品生产和检测操作监管。

In your response, you indicated that your firm is asmall company and does not have the resources for a quality unit. You statedthat you are responsible for reviewing and approving all quality relateddocuments. Your response was inadequate. Regardless of the size of yourcompany, as a drug manufacturer, you must have a quality unit that isresponsible for and authorized to perform certain operations.

  在你们的回复中，你们说你们公司是个小公司，没有质量部门资源。你们声称你们会负责审核和批准所有质量相关文件。你们的回复是不充分的，无论你们公司规模多大，作为一个药品生产商，你必须具备一个质量部门，负责并有权力执行特定的操作。

In response to this letter, explain how you willestablish defined roles and responsibilities for personnel performing theduties of your quality unit. These individuals should have appropriateauthority and sufficient resources to carry out their responsibilities toensure consistent drug quality.

在回复此函时，请解释你们将如何为执行你们质量部门工作的人员建立定义角色和职责。这些人员应具备适当的职责和足够的资源来履行其职责以确保药品质量一致。

4.      Your firm failed toestablish adequate written procedures for production and process controldesigned to assure that the drug products you manufacture have the identity,strength, quality, and purity they purport or are represented to possess (21CFR 211.100(a)).   你公司未建立设计用以确保你们生产的药品具备其理应具备的鉴别、剂量、质量和纯度的生产和工艺控制书面程序 (21 CFR 211.100(a)) 。  

Your firm lacked process validation for your OTC   (b)(4)product, including an ongoing program for monitoring process control to ensurestable manufacturing operations and consistent drug quality.

你公司缺少对你们 OTC 药品 XX 的工艺验证，包括监测工艺控制的持续计划以确保生产操作稳定和药品质量一致。

See FDA’s guidance document,   Process Validation:General Principles and Practices, for information on approaches that FDAconsiders appropriate elements of process validation, at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf .

参见 FDA 指南文件“工艺验证：一般原则和规范”。

You did not address your process validation plan inyour response.

你们在回复中未说明你们的工艺验证计划。

In response to this letter, provide your validationplan. Include your timeline for performing process performance qualificationfor your drug products as well as your approach for monitoring batch-to-batchvariations on an ongoing basis.

在回复此函时，请提交你们的验证计划，在其中包括对你们药品实施工艺性能确认的时间表，以及持续监测批间差异的方法。

5.      Your firm failed toprepare batch production and control records with complete information relatingto the production and control of each batch of drug product produced (21 CFR211.188).   FDA警告信：韩国It’S Hanbul Co., Ltd.; dba Hanbul Cosmetics 20180329