New policy for dissolution and disintegrationtesting in Ph. Eur. Monographs
EP各论中溶出度和崩解度测试的新政策
European Pharmacopoeia
Monograph
News
10 December 2020
Strasbourg, France
Over the last few years, the European Pharmacopoeia(Ph. Eur.) has been elaborating monographs on medicinal productscontaining chemically defined active substances, applicable toimmediate-release solid dosage forms (tablets, capsules).
在过去的⼏年中，欧洲药典⼀直在撰写含有明确化学成分的速释固体制剂（⽚剂，胶囊剂）的各论。
王世尧These monographs include a mandatory test fordissolution or disintegration. However, in justified and authorised cases,manufacturers may propose another procedure and/or, where appropriate,different acceptance criteria as part of their marketing authorisationapplication. This is indicated in the monographs by the sentence:
这些各论包括关于溶解或崩解的强制性测试。但是，在合理的情况下，制造商可以提议另⼀种⽅法和/或在适当时提出不同的接受标准，作为其上市许可申报的⼀部分。这在各论中⽤以下句⼦表⽰：
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The tablets comply with the test and the acceptance criterion describedbelow, unless otherwise justified and authorised.
这些⽚剂应符合以下所述的测试和接受标准，另有说明和批准者除外。
Since the result of the dissolution test may beaffected by the formulation and/or the manufacturing process, the Ph. Eur.Commission launched a substantive examination of users’ expectations withregard to this test in medicinal product monographs.
由于溶出度测试的结果可能会受到配⽅和/或⽣产过程的影响，因此，欧洲药典委员会对药品各论中的使⽤者对该测试的期望进⾏了实质性检查。
Users in the pharmaceutical industry, the licensingauthorities, national pharmacopoeias and OMCLs, for example, were thereforeinvited to participate in a survey in January 2019.
因此，制药⾏业的⽤户，如药监当局、国家药典和OMCL被邀请参加了2019年1⽉的调查。
Three options were proposed:
期间提出了三种⽅案：
北留中学
1.keep a mandatory dissolution test in the monographs; 在各论中保留强制检测溶出度
2.include a dissolution test as an example in the monographs; 在各论中加⼊⼀种溶出度检测作为例⼦
轮廓度3.do not include a dissolution test since the dosage form monographs on Tablets (0478) and Capsules (0016)
contain the requirement to carry out such a test, in addition to the preions of guideline ICH Q6A. 不加⼊溶出度检测，因为除了ICH Q6A指南中所述要求外，⽚剂各论（0478）和胶囊各论（0016）中已有执⾏此类检测的要求
Based on the results of the survey and on experiencegained by other pharmacopoeias elaborating such monographs, a compromise wasfound and adopted at the 168th session of the European Pharmacopoeia Commission(November 2020). The latter decided that a dissolution or disintegration testwill be included in each medicinal product monograph on an immediate-releasesolid dosage form.
根据调查结果以及其他药典对此类专题论⽂的研究经验，在欧洲药典委员会第168届会议（2020年11⽉）上到了折衷⽅案并予以采纳。欧洲药典委员会在所有速释固体制剂各论中放进溶出度或崩解度测试项⽬。
The details of the scope of such a test and theconditions for its use in a marketing authorisation application will beincluded in the General Notices (Chapter 1 of the Ph. Eur.). An excerpt isshown below:
此类测试的范围及其在上市许可申报中使⽤的条件的详细信息将包含在通则中（欧洲药典第1章）。摘录如下所⽰：
“In line withthe relevant guidelines applied nationally or regionally (such as the ICH Q6Aguideline) and with the relevant Ph. Eur. dosage form monograph, asuitable product-specific dissolution test ha
s to be proposed by the applicantfor routine quality control to confirm batch-to-batch consistency. This testmust be described in the MAA for submission to the competent authority, unlessthere is data justifying the replacement of the dissolution test by adisintegration test (see below). The demonstration of the suitability of thedissolution test has to be made by the applicant to the satisfaction of thecompetent authority.
“根据国家或地区适⽤的相关指南（例如ICH Q6A指南）以及相关的欧洲药典制剂各论，申请⼈必须提出适当的针对产品的溶出度测试进⾏⽇常质量控制，以确认批次之间的⼀致性。除⾮有数据证明⽤崩解度测试代替溶出度测试是合理的（见下），否则必须在MAA中描述该测试以提交给药监当局。申请⼈必须证明溶解度测试的适⽤性，并使主管当局满意。
Where appropriate, a dissolution test is described inan individual monograph on a medicinal product. In such cases, the applicantmay either select the monograph dissolution test or develop an in-housedissolution test as the product-specific dissolution test. In any case, theapplicant has to demonstrate the suitability of the selected test to the satisfactionof the competent authority.
在适当的情况下，在针对药物的单个各论中描述了溶出度测试。在这种情况下，申请⼈可以选择各论溶出度测试，也可以开发内部溶出度测试作为特定产品的溶出度测试。⽆论如何，申请⼈必须证明所选测试的适⽤性，使药监当局满意。浦东新区空气质量
If an in-house dissolution test is proposed,justification for not selecting the monograph dissolution test anddemonstration of compliance with the monograph dissolution test is normally notrequested in the MAA.
如果提议进⾏内部溶出度测试，则在MAA中通常不要求论证为何不选择各论溶出度测试，以及证明符合各论溶出度测试的理由。
However, when tested, the medicinal product has tocomply with the monograph dissolution test, unless otherwise justified by theapplicant.
但是，在进⾏测试时，药品必须符合各论溶出度测试，申报⼈另有论证者除外。
Where a given medicinal product does not comply withthe monograph dissolution test and this product is approvable by a competentauthority, then the competent authority shall bring this to the attention ofthe Ph. Eur. Commission so it can review the monograph and revise it whereappropriate.”
如果指定的药品不符合各论中的溶出度测试，且该产品经药监当局批准，则药监当局应将此事提请欧洲药典委员会注意，以便委员会对各论进⾏审查并在适当时进⾏修改。”
Consequently, the following monographs have beenrevised to delete the sentence in italics mentione
d above and to add a footnotereferring to the General Notices:
因此，对以下各论进⾏了修订，以删除上述⽤斜体字表⽰的句⼦，并添加脚注引⽤该通则：
•Deferiprone tablets (2986)
•Deferiprone tablets (2986)
•去铁酮⽚（2986）
•Dronedarone tablets (3038)
•决奈达隆⽚（3038）
•Lacosamide tablets (2989)
•拉考酰胺⽚（2989）
•Raltegravir chewable tablets (2939)
•雷特格韦咀嚼⽚（2939）
•Raltegravir tablets (2938)
•拉尔格韦⽚（2938）
澳洲唐人街•Regorafenib tablets (3023)
•雷⼽⾮尼⽚（3023）
•Riociguat tablets (3079)
•⾥奥西⽠⽚（3079）
•Rivaroxaban tablets (3021)
•利伐沙班⽚（3021）
•Rosuvastatin tablets (3008)
•罗苏伐他汀⽚（3008）
•Sitagliptin tablets (2927)
•西他列汀⽚（2927）
•Sorafenib tablets (3022)
•索拉⾮尼⽚（3022）
•Ticagrelor tablets (3097)
•替卡格雷⽚（3097）
These monographs and the revised General Notices willbe published in Supplement 10.6.这些各论和修订后的通则将在增补10.6辑中发布。
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