【药企】欧盟GMP新的附录16开始实施

新的附录16开始实施ThenewAnnex16"CertificationbyaQualifi



新的附录16开始实施

The new Annex 16 "Certification by a Qualified Person and Batch Release" will become effective as of 15 April 2016.

新的附录“QP认证和批放行”将自2016年4月15日起开始生效。

It is centrally pointed out that the main duty of a Qualified Person (QP) is the certification of batches. In this context, the QP must personally ensure that the responsibilities listed under Chapter 1.6 are fulfilled. Chapter 1.7 lists many other responsibilities to be guaranteed by the QP. However the related activities can be delegated and the QP can rely on the respective quality management systems. Yet, the "QP should have on-going assurance that this reliance is well founded" (1.7). The 21 responsibilites listed include amongst others:

其中指出QP的主要任务就是批认证。在此情况下，QP必须以个人名义确保已履行第1.6款中列出的职责。第1.7条中列出了许多由QP来保证的其它职责。但是，相关活动可以委托，QP可以依赖于相应的质量管理体系。但是，“QP应该一直确保此依赖性已经建立好了”（1.7）。列出的21项职责中包括以下：

• The starting materials used comply with the requirements and the supply chain is known and under control.
• 所用的起始物料符合要求，其供应链已知且受控。
• The necessary audits have been carried out and the audit reports are available.
• 必要的审计已实施，有审计报告。
• The manufacturing processes and testing methods are validated and in accordance with the marketing authorisation.
• 生产工艺和测试方法经过验证，符合上市许可内容。
• Changes have been assessed and completed accordingly.
• 变更经过评估，并已相应完成。

In this context, it is important to mention that the Annex clearly highlights that the overall responsibility (safety, quality and efficacy) for a medicinal product lies with the marketing authorization holder (MAH). "However, the QP is responsible for ensuring that each individual batch has been manufactured and checked (…) in accordance with the requirements of the marketing authorisation (MA) and with Good Manufacturing Practice (GMP)" (see general principles).

在此情况下，要重点提到的是附录清楚强调了对于一个药品，上市许可持有人（MAH）的总体职责（安全、质量和有效性）。“但是，QP负责确保每个批次均根据上市许可（MA）的要求进行生产和检查……，并符合GMP要求”（参见通则）。

In cases where the QP has to rely on the functioning QM system of another site, the QP must ensure that a documented review and permission of audit reports by third parties is available.

如果QP不得不依赖于另一个工三年的QM体系起作用，则QP必须确保有书面审核，并经允许可获取第三方审计报告。

Another important section clarifies the role of the QP with regard to deviations and includes a few elements from EMA's position paper on QP Discretion (published in February 2006 and updated in January 2008). Chapter 3 of the new Annex describes the "handling of unexpected deviations". A batch with an unexpected deviation concerning the manufacturing process may be certified if the result of a risk analysis performed shows that "the potential impact of the deviation on quality, safety or efficacy of the batch(es) concerned and conclusion that the impact is negligible." In cases where a deviation concerns specification defined in the marketing authorisation as essential for the release (OOS; out of specification), the QP will still have no scope left.

另一个重要的部分说明了QP在偏差方面的作用，在EMA关于QP处置权（2006年公布，2008年1月更新）的立场文章中包括了几个要素。新附录的第3章描述了“非预期偏差的处理”。当一个批次的生产工艺发生非预期偏差时，如果所进行的风险分析的结果显示“偏差对相关批次质量、安全或有效性有潜在影响，结论是影响可以忽略”，则可以认证放行。如果发生一个不符合上市许可中定义的对放行具有重要意义的质量标准偏差（OOS），则QP就不能任意行事了。

During the consultation phase, interest groups have expressed their concerns with regard to the sampling of imported products. Now, the new Annex 16 makes clear that "samples may either be taken after arrival in the EU, or be taken at the manufacturing site in the third in accordance with a technically justified approach which is documented within the company's quality system. (…) Any samples taken outside the EU should be shipped under equivalent transport conditions as the batch that they represent."

在征求意见阶段，利益相关团体已表达了其对于进口药品的取样方面的担心。现在，新的附录16明确说“样品可以在其到达欧盟之后取，也可以在第三国生产场所根据公司质量体系书面说明，经过技术论证的方法取样（……）。所有在欧盟境外所取样品均应在与其所代表的批产品相等同的运输条件下运输。”

Regarding any requirements on import, the new Annex 16 "Certification by a Qualified Person and Batch Release" has been kept relatively short. Those requirements will probably be set in the newAnnex 21.

关于进口的要求，新的附录16保持相对较短。这些要求可能会在新的附录21里来设定。

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