12月10日，就溶出度试验的相关要求，欧洲药典委员会发布一项通知。基于其168届会议的结论，对于速释固体制剂，将在每个药物专论中包括溶出度或崩解检验。同时将在通则中提出要求：上市许可申请人必须提出针对产品的适当溶出度试验，以进行常规的质量控制，确认批次间的一致性。申请人必须证明溶出度试验的适用性，并获得主管当局的认可。

溶出度试验的现状

Over the last few years, the European Pharmacopoeia (Ph. Eur.) has been elaborating monographs on medicinal products containing chemically defined active substances, applicable to immediate-release solid dosage forms (tablets, capsules).

在过去的几年中，针对速释固体制剂（片剂/胶囊剂）的化学成分药物，欧洲药典一直在撰写相应的专论。

These monographs include a mandatory test for dissolution 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 authorisation application. This is indicated in the monographs by the sentence:

这些专论包括对溶出度或崩解的强制性检验。但是，在论证和批准的情况下，生产商可以提议另一种程序和/或提出不同的可接受标准（适当时），作为其上市许可申请的一部分。关于这一点，在专论中有以下句子可以表明：

The tablets comply with the test and the acceptance criterion described below, unless otherwise justified and authorised.

除非另有论证和批准，否则片剂应符合以下所述的检验和可接受标准。

Since the result of the dissolution test may be affected by the formulation and/or the manufacturing process, the Ph. Eur. Commission launched a substantive examination of users’ expectations with regard to this test in medicinal product monographs.

由于溶出度试验的结果可能会受到处方和/或生产工艺的影响，因此，就用户在药品专论中对该检验的期望，欧洲药典委员会进行了独立的的审查。

问卷调查

Users in the pharmaceutical industry, the licensing authorities, national pharmacopoeias and OMCLs, for example, were therefore invited to participate in a survey in January 2019.

例如，2019年1月，来自制药行业、许可当局、国家药典和OMCL的用户被邀请参加了问卷调查。

Three options were proposed:

当时，提出了三个选项：

keep a mandatory dissolution test in the monographs;

include a dissolution test as an example in the monographs;

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 prescriptions of guideline ICH Q6A.

在专论中，保留强制性的溶出度试验；

在专论中，溶出度试验以示例的方式列出

不包含溶出度试验，因为在片剂（0478）和胶囊（0016）剂型专论中，除了包含指南ICH Q6A的要求外，还包含了进行该检验的要求。

欧洲药典委员会结论

Based on the results of the survey and on experience gained by other pharmacopoeias elaborating such monographs, a compromise was found and adopted at the 168th session of the European Pharmacopoeia Commission (November 2020). The latter decided that a dissolution or disintegration test will be included in each medicinal product monograph on an immediate-release solid dosage form.

根据调查结果和其它药典编写此类专论的经验，在欧洲药典委员会第168届会议（2020年11月）上找到了折衷方案，并予以采纳。后者决定：对于速释固体制剂，溶出度或崩解检验应包括在上每个药物专论中。

The details of the scope of such a test and the conditions for its use in a marketing authorisation application will be included in the General Notices (Chapter 1 of the Ph. Eur.). An excerpt is shown below:

有关此类检验的范围及其在上市许可申请中使用的条件，其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 with the relevant guidelines applied nationally or regionally (such as the ICH Q6A guideline) and with the relevant Ph. Eur. dosage form monograph, a suitable product-specific dissolution test has to be proposed by the applicant for routine quality control to confirm batch-to-batch consistency. This test must be described in the MAA for submission to the competent authority, unless there is data justifying the replacement of the dissolution test by a disintegration test (see below). The demonstration of the suitability of the dissolution test has to be made by the applicant to the satisfaction of the competent authority.

“与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剂型专论相一致，申请人必须提出针对产品的适当溶出度试验，以进行常规的质量控制，确认批次之间的一致性。除非有数据证明用崩解检验代替溶出度试验是合理的，否则必须在MAA中描述该检验，以提交主管当局。申请人必须证明溶出度试验的适用性，并获得主管当局的认可。

Where appropriate, a dissolution test is described in an individual monograph on a medicinal product. In such cases, the applicant may either select the monograph dissolution test or develop an in-house dissolution test as the product-specific dissolution test. In any case, the applicant has to demonstrate the suitability of the selected test to the satisfaction of the competent authority.

在适当的情况下，在针对药物的单个专论中将对溶出度试验进行描述。在这种情况下，申请人可以选择专论溶出度试验，也可以开发内部溶出度试验，作为特定产品的溶出度试验。无论如何，申请人必须证明所选检验的适用性，使主管当局满意。

If an in-house dissolution test is proposed, justification for not selecting the monograph dissolution test and demonstration of compliance with the monograph dissolution test is normally not requested in the MAA.

如果提议进行内部溶出度试验，则在MAA中通常不要求论证不选择专论溶出度试验的理由，也不要求证明符合专论溶出度试验。

However, when tested, the medicinal product has to comply with the monograph dissolution test, unless otherwise justified by the applicant.

但是，除非经过申请人另行论证，否则在进行检验时，药品必须符合专论溶出度试验。

Where a given medicinal product does not comply with the monograph dissolution test and this product is approvable by a competent authority, then the competent authority shall bring this to the attention of the Ph. Eur. Commission so it can review the monograph and revise it where appropriate.”

如果给定的药品不符合专论中的溶出度试验，且该产品经主管当局批准，则主管当局应将此事提请欧洲药典委员会注意，以便该委员会可以审查专论，并在适当时进行修改。”

后续修订

Consequently, the following monographs have been revised to delete the sentence in italics mentioned above and to add a footnote referring to the General Notices:

因此，对以下专论进行了修订，以删除上述用斜体字表示的句子，并添加引用“通则”的脚注：

Deferiprone tablets (2986)

Dronedarone tablets (3038)

Lacosamide tablets (2989)

Raltegravir chewable tablets (2939)

Raltegravir tablets (2938)

Regorafenib tablets (3023)

Riociguat tablets (3079)

Rivaroxaban tablets (3021)

Rosuvastatin tablets (3008)

Sitagliptin tablets (2927)

Sorafenib tablets (3022)

Ticagrelor tablets (3097)

去铁酮片（2986）

决奈达隆片（3038）

拉考酰胺片（2989）

拉格韦韦咀嚼片（2939）

雷格列韦片剂（2938）

雷戈非尼片（3023）

里奥西瓜片（3079）

利伐沙班片（3021）

瑞舒伐他汀片（3008）

西他列汀片（2927）

索拉非尼片（3022）

替卡格雷片（3097）

These monographs and the revised General Notices will be published in Supplement 10.6.

这些专论和经修订的通则将在补编10.6中发布。

Ref:

New policy for dissolution and disintegration testing in Ph. Eur. Monographs. 10 DECEMBER 2020. EDQM