20160210 ECA新闻：展望：2016年GMP有何新进展？ - 药群论坛

The previous year 2015 was an eventful year. Again there were new developments in the GMP environment as well as announcements of changes that preoccupied the pharmaceutical industry. 2016 won't be less exciting, also because now many of the new requirements must be implemented. But aso novelties have to be expected. Here are a few highlights:

之前的2015年是多事的一年。在GMP环境再次有新的发展，制药行业也有不少变化宣布。2016年也不会差，也因为现在许多新的要求必须实施了。还有一些创新值得期待。这里讲一些重点内容。

A new Annex might be added to the EU GMP Guide: Annex 21 for "Importers of Medicinal Products". The current concept paper doesn't reveal much information but a first draft of the new Annex can be expected soon for public consultation. The discussions of the requirements for import in the context of the revision of Annex 16 ("Certification by a QP and Batch Release") were the impulse for the new document. The future Annex is aimed at importers and will cover requirements regarding import activities which are not part of other GMP regulations so far.
EU GMP指南中可能会增加一个新的附录：附录21“药品进口商”。目前的概念文章并没有透露出许多信息，但可以期待新附录的第一版草案会很快公布征求意见。在附录16（QP证明和批放行）修订后，对进口要求的讨论是新文件产生的原因。将来的附录针对的是进口商，会包括关于进口活动的要求。这些进口活动截止目前并不在其它GMP法规里面。

A concept paper on Annex 1 of the EU GMP Guide (Manufacture of sterile Medicinal Products) is currently running. A first draft of the revised Annex should also be expected soon for public consultation. The revision is not supposed to create new expectations, but it will contain some adjustments like for example the consideration of other international sets of rules (FDA Aseptic Guide, ICH Q8, Q9, and Q10) and the clarification of requirements which have been until now controversial or ambiguous. The US-American IEST published the new version of ISO 14644:2015 "Classification of air cleanliness by particle concentration" already last year. It is to be expected that also here the contents will be considered.

EU GMP指南附录1的概念文章（无菌药品的生产）正在进行中。预期修订附录的首版草案很快就会公布征求意见。修订版并不会创建新的要求，但会包括许多调整，例如考虑其它国际规定（FDA无菌指南，ICH Q8，Q9和Q10），以及对规定要求的澄清，这些要求到目前为止还是相互矛盾或模糊不清的。美国IEST新版本ISO 14644：2015“根据颗粒浓度进行空气清洁度分类”已于去年公布。其内容也是需要考虑的。

Annex 17 of the EU GMP Guide (Real Time Release Testing) is to be completely modified. The change of name alone in the current draft signalises a complete reorientation. In the end, the curent annex 17 "Parametric Release" was restricted to be used for the routine release of products sterilised in the final container without sterility tests on the basis of sterilisation parameters. Now, the revision also includes the implementation of the principles of ICH Q8, Q9, and Q10 which can also be applied to other products. Afterwards certification and release of a batch can be based on the monitoring and the control of critical process parameters and relevant material characteristics, sufficient product and process knowledge and a combination of in-process monitoring and controls which provide sufficient data. Then, a batch release would be justifiable without re-testing a sample of the finished product. For this purpose, the Real Time Release approach must be part of the marketing authorisation. The performance of finished product analytics won't be accepted if the RTR test approach has delivered unfavourable or non-compliant results.

EU GMP指南附录17（实时放行测试）将要进行完全修订。目前的草案对名称的改变就预示着其完全不同的定位。在结尾，现行附录“参数旅行”被限制于用于在最终包装里灭菌的药品的根据灭菌参数进行常规放行，不需要进行无菌测试。现在，修订版本也包括ICH Q8，Q9，Q10概念的实施，它们也适用于其它药品。之后的认证和批放行可以是根据对关键工艺参数和相关物料属性、充分的药品和工艺知识和中控监测和提供足够数据的控制的结合。这样不需要对成品进行取样再次测试也可以判定是否对批次放行。为此，实时放行方法必须是上市许可的一部分。如果RTR测试方法显示出不好或不符合的结果，则成品分析的结果不能被接受。

The US Food and Drug Administration (FDA) has started an initiative to use so-called Quality Metrics for planning its risk-based inspections. A first draft was published in July 2015 for consultation from associations and the industry. FDA's wish is - after the entry into force - to collect defined quality characteristics i.e. "Quality Metrics" from manufacturers via an electronic portal. With these metrics, the FDA will calculate specific statistics which should enable a risk-based management and planning of FDA's inspections.

美国FDA已开始倡议使用所谓质量量度用于计划其基于风险的检查。首版草案于2015年7月公布征求协会和行业的意见。FDA的希望是，在实施之后，通过电子端口从生产商处收集指定的质量属性，即“质量量度”。根据这些量度，FDA会计算指定的统计指标，根据这些指标来进行基于风险的管理，制订FDA检查计划。

Concerning this, a "Quality Metrics Technical Conformance Guide" should be released in 2016. This is referred to in the list of all guidelines published by the CDER (Center for Drug Evaluation and Research) which are planned this year. The list comprises 102 documents in total divided into 15 categories. The following documents should be highlighted:

There will be some new developments in the area of Investigational Medicinal Products (IMPs). Last year, the EU Commission published four new public consultations on IMPs. They concern both manufacturing (GMP) as well as clinical trials (GCP) for human medicinal products. The reason is that as soon as Regulation (EU) No 536/2014 will apply to clinical trials, Directive 2003/94/EG won't be applicable to IMPs any longer. Then, they will have to be manufactured or imported according to the regulations of Delegated Acts or other specific regulations; in other words, new documents have to be created. This could also endanger Annex 13. The question is currently discussed to drop it and replace it with another legal act or to revise it.

在非临床药品（IMPS）领域有一些新的发展。去年，欧盟委员会公布了IMP的4份新文件征求意见。这些文件兼有人用药品的生产（GMP和临床试验（GCP）。其理由是一旦法规EU 536/2014适用于临床试验，指令2003/94/EC就不再适用于IMPS了。这样，他们就不得不按委托监管法案或其它指定法规的规定进行生产或进口了。换句话说，必须创建新的文件。这可能会让附录13陷入危机。现在正在讨论的问题是不要管它，而采用另一个法案来替代或修订之。