MHRA对交叉污染和PDE的诠释

一片红云

The British inspectorate MHRA has recently published an interpretation that goes into detail on the use of health based exposure limits and explains the cases where EMA's new concept can be applied. One essential element of that concept is EMA's Q&A Paper describing when a product should be classified as highly active.
英国MHRA最近发布了一份诠释，详细说明了基于健康的暴露限的使用，并解释了EMA新概念可以应用的案例。该概念的一个基本要素是EMA的问答文中描述的什么时候一个产品应被列为高活性。

After the revisions of Chapters 3 and 5 of the EU GMP Guide in 2015, more attention has been given to the topic cross contamination.  At the same time, a guideline of the EMA was published introducing the concept of PDE values. Those health based exposure limits should be used to assess whether a product can be produced in a dedicated or in a multipurpose facitility. The background for that was the request of the pharmaceutical industry to be able to decide itself on a risk-based approach whether a product can be produced in a multipurpose facitility, or not. Previously, there was a rather inconclusive list requiring a dedicated facility e.g. for special products, special cytototix products or hormones. Because the 1/1,000 dose criterion used so far isn't really scientific and therefore not very suitable for a risk-based approach, the EMA introduced the PDE concept. This has led to some discussion as the calculation without toxicological/pharmocaological data and knowledge is not so clear-cut.
在2015年对EU GMP指南第3章和第5章进行修订之后，交叉污染的主题受到了更多关注。同时，EMA发布的一份指南介绍了PDE值的概念。这些基于健康的暴露限应被用来评估是否一个产品可以在专用设施或多功能设施中进行生产。之前，有一个近乎结论似的清单，其中的产品要求使用专用设施，例如，特殊产品、特殊细胞毒素产品和荷尔蒙类产品。由于到目前为止，所使用的1/1000剂量标准真的不科学，因此并不是很适合于基于风险的方法，因此EMA介绍了PDE概念。这引发了一些讨论，因为没有毒性/药性数据和知识的情况下，这样的计算无法进行。

Now, the MHRA states that the full use of  EMA's guide for the calculation of the PDE values is only necessary for so-called "highly hazardous" products. To answer the question whether a product is highly hazardous or not, one can refer to the new Q&A document of the EMA. Nevertheless, one should keep in mind that the assessment of hazard by means of EMA's paper, scientific data are also required which would also enable the calculation of the PDE limits.
现在MHRA说全面应用EMA关于PDE值计算指南只是对于“高有害”物质才是有必要的。为了解答一个产品是否高有害性，大家可以参照新的EMA问答文件。不论如何，大家要谨记，根据EMA文中方法进行的危害分析也需要科学数据，用这些数据也可以计算PDE限度。

However, Health Based Exposure Limits (HBELs) should be determined for all products. If a product is classified as not "highly hazardous", the 1/1,000 dose criterion can still be used. Now the question remains why the MHRA has published its interpretation before the final adoption of EMA's Q&A  document. Generally, the cleaning limits calculated by means of the 1/1,000 dose criterion are more conservative than when using the PDE value as a basis.
但是，应该计算所有产品的基于健康的暴露限（HBEL）。如果有一个产品被分类为非“高危害”产品，则仍可以使用1/1000剂量标准。现在问题还是在于为什么MHRA要在EMA问答文件最终采纳之前发表其诠释。一般来说，采用1/1000剂量标准来计算清洁限度其实比起采用PDE值来说更为保守。

EMA's Q&A document is currently at the draft stage. Comments can be submitted until the end of April to the EMA.
EMA问答文件目前还在起草阶段。相关意见可以在4月底之前提交至EMA。

静水蓝心

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xqliu

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syhorchid

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梦魂牵绕♂

被PDE整死了

子政

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beiwei5du

" Generally, the cleaning limits calculated by means of the 1/1,000 dose criterion are more conservative than when using the PDE value as a basis."为什么这么理解？？这句话的前提应该是针对于not highly hazardous product吧。

Q4. Can calculation of HBELs be based on clinical data only (e.g. to establish the HBEL on
1/1000th of the minimum therapeutic dose)?

A: Many existing commercial products and new products for which clinical safety profiles are well -
established and that do not belong to the highly hazardous category (see response to Q2) have a
favourable therapeutic index (also referred to as the therapeutic window or safe ty window). This
means that unwanted or adverse health effects (that may have been identified as toxic effects in
animal studies at high doses) may occur  - if at all  - at dose levels orders of magnitude above the
therapeutic dose range and the pharmacologi cal activity would therefore be the most sensitive/critical
effect. In this situation, therapeutic dose information could be used as the ‘Point of Departure’ for
calculation of an HBEL (e.g. the PDE). Under these circumstances, HBEL based on the 1/1000th
minimum therapeutic dose approach would be considered as sufficiently  conservative and could be
utilised for risk assessment and cleaning purposes.  

zhaozxche

学习一下啦，谢谢提供分享

小金库

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