EMA防止交叉污染问答 20161215

beiwei5du

chemstar 发表于 2017-3-15 08:15
@julia朱玉姣 哪是啥呢？与PDE、ADE有什么关系呢？

应该属于一种包含关系，比如在一些情况下1/1000日剂量也可以作为一种HBELs吧

逆天的三胖

好好学习，天天向上

beiwei5du

冷血无情 发表于 2017-3-13 09:07
朱版主，那个Q4是什么意思？通常情况下，千分之一日最低治疗量可以被默认为最低日暴露量？Q6是通常来说，千 ...

“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 pharmacological activity would therefore be the most sensitive/critical
effect.”楼主这句话翻译可能有点出入，这样翻译可能会更好：
这意味非预期或不良健康反应（这可能在动物研究中高剂量时被识别为毒性反应）可能发生，如果真的有，也是发生在高于治疗剂量几个数量级以上的剂量水平上，并且此时药理学活动才被作为最敏感和关键的反应。

beiwei5du

chemstar 发表于 2017-3-15 08:10
个人认为它的意思是对于普通药品的限度计算不用考虑毒理数据。我的理解是否对，朱版主@julia朱玉姣

For those of you that are not familiar with this document, it is a series of fourteen (14)
questions and answers relating to implementation of Health Based Exposure Limits
(HBELs). Before I start on the 14 questions, a discussion of HBEL versus PDE values
requires some clarification. The more general term is HBEL. PDE is only one method to
derive a HBEL. Unfortunately the 2014 EMA is sometimes read as requiring PDE values
for all actives. It should be clear from reading that document that a PDE is only one
avenue for establishing a HBEL. That 2014 document also discusses using the TTC
concept for genotoxic materials, as well as stating for certain products, like biotechnology
actives and product where the most relevant safety data is on humans, the PDE formula
maynotbe appropriate.

That said, the wording of the EMA document may contribute to that misreading. The
beginning of Section 4.1 states “The procedure proposed in this document for
determination of health based exposure limits for a residual active substance is based on
the method for establishing the so-called Permitted Daily Exposure (PDE)… .” Obviously
the PDE is not theonlyprocedure to establish a HBEL given in that 2014 document. In
addition, Section 6 of the 2014 document is titled “Reporting of the PDE determination
strategy”; it would seem appropriate if there were other means of determining a HBEL,
that section should have been titled “reporting of the HBEL determination strategy”.
Fortunately the new draft Q&A clarifies this and emphasizes the general idea of a HBEL
as compared to one embodiment of it (the PDE).

beiwei5du

这个文件应该还是一个draft文件，以下是一些评论文。仅供参考！

August 2017 EMA's Q&A Clarification: Part 2

July 2017 EMA's Q&A Clarification: Part 1

赵旭锋

高活性、HBEL
这段时间被这些折腾惨了

小刀

谢谢分享…………

王远

谢谢分享，学习学习

zhangxinjiang

谢谢分享，先学习

句点

谢谢分享，非常受用