【技术交流】在CEP中引用另一个CEP作为起始物料

Certification ofsuitability to Monographs of the European Pharmacopoeia

Use of a CEP todescribe a starting material in an application for another CEP

CEP证书

在CEP中引用另一个CEP作为起始物料

Address: 7 AlléeKastner, CS 30026

F-67081Strasbourg (France)

Tel: +33 (0) 388 41 30 30 – Fax: +33 (0) 3 88 41 27 71 - e-mail: cep@edqm.eu

Internet: http://www.edqm.eu

Introduction 介绍

As described inthe EDQM guideline, Content of the dossier for chemical purity andmicrobiological quality, PA/PH/ CEP (04) 1 current version, “for startingmaterials described in the European Pharmacopoeia certificates of suitabilitycan be provided , if available” to replace the information on the manufactureand control of the starting material.

正如EDQM的指南“化学纯度和微生物质量文件内容，PA/PH/ CEP (04) 现行版本1”中所述，“如果所采用的起始物料引用已有CEP”，可以替代对起始物料的生产和控制资料。

The use ofcertificates of suitability (CEPs) for starting materials in an application fora chemical CEP is applicable where there is a monograph of the EuropeanPharmacopoeia for the substance identified as a starting material as theavailability of such a monograph is a prerequisite to the issue of a CEP.Typically the substances concerned are therefore active substances and if theCEP were not available would usually be regarded as intermediates in thesynthesis. The CEPs can be accepted as the manufacturing process and controlsbeing applied have been assessed before the CEP has been granted for the startingmaterial.

如果在欧洲药典中有一个物质的各论，而该物质被作为起始物料，则在化学CEP的申请中，可以引用该物料的CEP。因此，这种情况下所讨论的起始物料一般是也是一种原料药，如果没有CEP，则通常会被作为是合成中的一个中间体。起始物料的CEP颁发前，如果生产工艺和控制已经被审评，可以被接受（被新CEP引用）。

It is thereforeappropriate to clarify the practical aspects of the use of one CEP for a startingmaterial in an application for another CEP.

因此需要澄清一下如何在实际中操作在一个CEP申报中引用另一个CEP作为其起始物料。

Conditions 条件

The startingmaterial must be the substance which is covered by the CEP being submitted.

起始物料必须是被已提交的CEP所包括的物质。

The CEPapplication for the starting material must have already been approved by theEDQM and the corresponding CEP must have been granted and be valid.

作为起始物料的CEP必须是已经由EDQM批准的，且相应的CEP必须已签发并有效。

A copy of theCEP for the starting material must be included in the submission for the newCEP and the box of access for the CEP must be completed appropriately.

起始物料的CEP复印件必须包括在新CEP申报材料中，CEP中的授权表必须填写完整。

The fullspecification described on the CEP for the starting material must be applied tothe starting material to allow release for use in the manufacturing process forthe new CEP.

在起始物料的CEP中的全套质量标准必须适用于起始物料，这样放行的物料均可以用于新CEP生产工艺。

LifecycleMaintenance 生命周期维护

Any regulatoryactivity on the CEP for the starting material must be complemented by theappropriate regulatory activity on the new CEP. Therefore if the CEP for thestarting material is revised then a copy of the revised CEP must be submittedas a revision to the new CEP.

针对起始物料的CEP的所有法规活动，新的CEP必须有适当的法规活动进行补充。因此，如果起始物料的CEP被修订，则修订后的CEP的复印件必须由新的CEP作为修订提交。

The submissionof a revised or renewed CEP for the starting material is considered as anannual notification except in the following cases:

除以下情况外，（新CEP为）修订或更新后的起始物料CEP的提交会被作为是年度通知：

—      The specification of the substance (starting material)covered by the revised or renewed CEP is changed, in which case a minorrevision by default should be submitted.

—      修订或更新后的CEP中物质（起始物料）的质量标准发生变更，此时默认申报为微小变更

—      There is a change to the manufacturing sites mentioned on the CEP forthe starting material (but no change in the specification of the startingmaterial), in which case an immediate notification should be submitted.

—      起始物料CEP上的生产场所发生变更（但起始物料的质量标准不变），此时应作为立即通知来申报

If the CEP forthe starting material is no longer valid (due to suspension, withdrawal orexpiry) then the CEP application which references it must be updated to eitherdelete the reference to this CEP (where there are multiple sources of startingmaterial described) or replace the reference to this CEP with details ofanother source of material. If the new source of material does not have a CEPthen it will be necessary to redefine the starting material to an appropriatepoint earlier in the synthesis and update the CEP dossier accordingly.

如果起始物料的CEP不再有效（由于搁置、撤销或过期），则引用该CEP的CEP申报必须更新，要么删除该引用（如果起始物料有多家来源），要么将对该CEP的引用替换为另一来源。如果新的原料来源没有CEP，则必须重新界定起始物料至适当的合成点，并对CEP文件进行相应地更新。

Transparency ofManufacturing Supply Chain 生产供应链的透明性

Since the startingmaterials covered by a CEP are typically active substances and would usually beregarded as intermediates in the synthesis if a CEP were not available, thedetails of the manufacturing sites involved in the manufacturing processdescribed in the CEP for the starting material should also be mentioned in thesection “3.2.S.2.1 Manufacturers” of the submission dossier for the new CEP.

由于被CEP覆盖的起始物料通常都是原料药，而在没有CEP时会作为合成中的一个中间体来对待，所以要新CEP的申报资料中的“3.2.S.2.1生产商”部分也要提供起始物料CEP中生产工艺部分的生产场所详细信息。

The details ofall manufacturing sites involved in the manufacturing process described in theCEP for the starting material will also be mentioned in the annex 1 of the newCEP which describes the manufacturing sites.

起始物料CEP中的生产场所详细信息还要在新CEP中列出

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