附录17实时放行测试：公开征求意见结果

GMP News
21/09/2016

Annex 17 on Real Time Release Testing: Results of Public Consultation

附录17实时放行测试：公开征求意见结果

On 15 September 2015, a consultation was launched on a draft revised Annex 17: Real Time Release Testing. Deadline for comments was 11 December 2015. Now, the feedback from the various stakeholders was published.

2015年9月15日，修订后的附录17“实时放行测试”开始公开征求意见。征求意见截止日期为2015年12月11日。现在公布的是来自不同干系人的反馈。

The reasons for the changes in the document are that the previous Annex 17 "only focused on the application of Parametric Release for the routine release of terminally sterilised products waiving the performance of a test for sterility on the basis of successful demonstration that predetermined and validated sterilising conditions have been achieved."

对文件进行变更的原因是之前的附录17“仅关注了最终灭菌药品日常放行用的参数放行应用，根据预定的成功证明和达到经过验证的灭菌条件来免除实施无菌测试”。

In the section "Scope" of the draft document it is pointed out that the Annex "is intended to outline the requirements for application of a Real Time Release Testing (RTRT) approach in manufacturing, where the control of critical parameters and relevant material attributes may be used as an alternative to routine finished product testing of medicinal products. The main aim of the changes to this guideline is to incorporate the application of RTRT to any stage in the manufacturing process and to any type of finished products, including active substances and intermediates."

在文件草案的“范围”部分指南该附录“意在列出实时放行测试（RTRT）方法在生产中的应用要求，其中可以使用关键参数控制和相关物料属性作为日常药品成品检查的替代方式。该指南变更的主要目的是将RTRT的应用结合到所有生产工艺步骤中，结合到所有类型的制剂生产中，包括原料药和中间体。”

Furthermore, the draft defines RTRT as "a combination of in-process monitoring and controls" that "may provide sufficient evidence to justify batch release without the tests being repeated on a sample of the finished product".

另外，草案将RTRT定义为“中控监测和控制的联合”，“它可以提供足够的证据来论证批放行不需要对成品样品进行重复检测”。

In addition the draft document emphasizes that "advances in the application of process analytical technology (PAT), quality by design (QbD) and quality risk management (QRM) principles to pharmaceutical development and manufacturing have shown that appropriate combination of process controls together with timely monitoring and verification of pre-established material attributes provides greater assurance of product quality than finished product testing (conventionally regarded as the end-product testing) alone."

此外，文件草案强调“过程分析技术（PAT）、质量源于设计（QBD）和质量风险管理（QRM）原则在药物研发和生产中的进一步应用已经显示出，相比于仅仅依赖成品检测（传统上作为最终产品检测），将工艺控制与及时监测和预先定义的物料属性核查恰当结合能更大程度地保障药品的质量。

The draft annex is based on elements of ICH Q8, Q9, Q10 and Q11 "and will detail regulatory expectations for a batch release system based on the information collected during manufacturing process, through product knowledge and process understanding and control."

附录草案是基于ICH Q8、Q9和Q11的要素，“并详细说明了根据生产过程中，通过产品知识和工艺了解和控制所收集的信息进行批放行体系的法规期望。”

Since the control strategy is dynamic and may change this should be handled as a life cycle approach requiring the use of quality risk management and knowledge management.  This is recently also highly discussed in relation with the new planned ICH Q12 Guideline on "Life Cycle Management".

由于控制策略是动态的，可能会发生变更，因此需要采用质量风险管理和知识管理工具，作为一个生命周期方法来管理。这点最近与也新计划的ICH Q12指南“生命周期管理”结合有很多讨论。

The results from the consultation can be found on the EudraLex Website. It is interesting to have a look on the comments and proposed modifications. These range from the required RTRT master plan up to the use of definitions. It will be interesting to see how the suggestions will find their way into a final version of the final Annex.

征求意见的结果可以在欧盟药事法官网上找到。看一下意见和建议的修改还是蛮有意思的。这些建议从所需的RTRT主计划直到定义的使用，范围很宽。看一下这些建议如何能进入附录最终版也是很有意思的。

来源：Julia