第二份名为
“2013年新的/修订撤销清单”
这是一份涉及所有指南文件变更,包括撤销的指南文件清单。每年有一份清单,并经常更新。这也是唯一公布已撤销指南的通告。
回到我们的故事。2013年初发布的指南日程中，提到一份准备于2013年发布的指南为 “在加工混合物均匀性（生产与产品质量办公室，Office of Manufacturing and Product Quality，OMPQ）”。列于 “药品生产质量管理规范 (CGMPs)/合规”项下。这表明，2013年CDER的指南计划的一部分是由药品生产质量办公室（OMPQ，之前的DMPQ（生产与产品质量处））发布的加工混合物均匀性指南。然而在2013年8月，在生产质量管理规范部分关于产品与工艺控制的问与答中出现四个“问题”。最近该部分的标题已被调整为“2级指南”，一个我并不熟悉的术语。四个“问题”中的第一个，问题15，表明： 15．FDA近日宣布撤销关于“混合粉体与成品制剂 — 中间过程剂量单位分层取样与评价”的指南草案。请问FDA对此指南文件的主要关注是什么？【生产与工艺控制问答指南-识林资讯】
接下来的三个其它“问题”，旨在详细了解药品生产质量办公室反对分层取样指南文件的细节。具体问答请见如下链接： Questions and Answers on Current Good Manufacturing Practices (CGMP) for Drugs
在该解释最初公布时（没有提供任何数据），分层取样指南文件草案仍列于药品审评和研究中心的指南文件清单中。还保持了数月，似乎拒绝“被撤销”。直至上周我才发现，它最终在指南页面消失了。我紧接着浏览了新的/修订的撤销清单，以了解它是否确实被撤销。直至今日（2013年12月13日），仍未被列为撤销（实际上此清单中没有任何指南被列为“撤销”）。
对于一份申请人用于在产品开发时确定达到达到在加工均匀性要求，以及在日常生产中遇到明显的在加工检测不合格时指导检查的重要指南来讲，这是一切似乎是非常奇怪的处理方式。此外，在CDER已在数月前表明新指南文件是计划一部分的情况下，为何在用新指南替代之前撤消现行指南。
声明通过一系列“致Dorothy Dix”问题来管理合规性的办公室现正考虑撤销如此重要的一份文件，远远不符合良好指南规范。
可确定的是，遵照 “粉体混合与制剂成品 — 中间过程剂量单位分层取样与评价” 指南草案指导其工艺开发与生产检查的申请人与生产商，现已没有任何OMPD可能认同的任何形式的指南。至于OMPD，他们明显需要良好指南规范的再培训。
2013年尚未结束，或许我们将会在年终前看到一份名为“在加工混合物均匀性”的新指南。 北京大学药物信息与工程研究中心 - Garth Boehm 博士 2013-12-14 翻译：识林-Kapok 2013-12-15
英文原文
An Interesting Story with No End – Yet!
FDA has something called “Good Guidance Practices”. The purpose of Good Guidance Practice is to ensure that any new or changed guidance is developed and communicated to regulated industry in a standard and predictable way that is fair to all concerned – in other words you should expect to know where to find new or changed guidance.
To help in this process, FDA publishes two lists. The first is called:
“Guidance Agenda: New & Revised Draft Guidances CDER is Planning to Publish During Calendar Year 2013 (See the Good Guidance Practices (GGPs) regulation on this Web page or 21 CFR 10.115 for details about the Guidance Agenda.)”
This is a list of all guidances proposed for development as new or revision if the same or a similar guidance already exists. This list serves as notice to industry of upcoming changes. If there is a change to the guidance plan during the year, the list is updated.
The second is called:
“New/Revised Withdrawn List for 2013”
This is a list of all guidance changes, including withdrawn guidances. There is a list for5 each year and it is updated frequently. It also serves as the only notice that a guidance has been withdrawn.
Now to our story. When the Guidance Agenda issued near the start of 2013, one of the guidances slated for issue during 2013 was “Uniformity of In-Process Mixtures (OMPQ)”. It was listed under the category “Good Manufacturing Practices (CGMPs)/Compliance”. This indicated that part of DCERs guidance plan for 2013 was the issue of a guidance on uniformity of in-process mixtures by the Office of Manufacturing and Product Quality (OMPQ, formerly DMPQ). However about August of 2013 four “questions” appeared in the Questions and Answers on Good Manufacturing Practices section concerning Production and Process Controls. Recently the header to this section has been restyled to call it “Level 2 Guidance”, a term with which I am not familiar. The first of the four “questions”, Question 15, states: 15. FDA recently announced the withdrawal of its draft guidance for industry on Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment. What were the Agency's major concerns with this guidance?
This is followed by three additional “questions” which aim to detail OMPQs objections to the Stratified Sampling guidance. You can find these questions and answers here: Questions and Answers on Current Good Manufacturing Practices (CGMP) for Drugs
At the time this explanation first published (they provide no dates), the Stratified Sampling draft guidance was still in CDERs Guidance list. It remained there for several months, apparently resisting “withdrawal”. When I looked for it last week, it had finally disappeared from the Guidance page. My next move was to go to the New/Revised Withdrawn list to see if it was in fact withdrawn. As of today (December 12, 2013) it is not listed as withdrawn (indeed there are no guidances listed as “withdrawn” in the list).
This all seems to be a very strange way of dealing with an important guidance that sponsors rely on both to establish that they meet in-process uniformity requirements in product development and to guide investigations when they encounter apparent in-process testing failures in routine manufacturing. In addition, why withdraw current guidance before replacing it with new guidance that CDER has signaled many months ahead was part of their plan.
The “announcement” that an important guidance is now considered withdrawn by the Office that administers compliance with that guidance via a series of “Dear Dorothy Dix” questions is about as far from Good Guidance Practices as you can get.
One thing is certain, sponsors or manufacturers relying on the draft guidance “Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment.” To guide their process development and manufacturing investigations are now without any form of guidance concerning what might be “acceptable” to OMPQ. As for OMPQ, they obviously need retraining in Good Guidance Practices.
Finally, 2013 is not over yet, perhaps we will see a new ”Uniformity of In-Process Mixtures” Guidance before the end of the year. 北京大学药物信息与工程研究中心 - Garth Boehm 博士 2013-12-14
（该指南日程详情，请参阅网页上的良好指南规范（Good Guidance Practices ，GGPs）规定或