EU: Quality of Drug Substance in the Dossier - Revised CPMP Guidelines

GMP News No. 462

9 September 2004

EU: Quality of DrugSubstance in the Dossier –
Revised CPMP Guidelines

The revised Note for Guidance on the European Drug Master FileProcedure was adopted by CPMP/CVMP in January/February 2004 and came into operation on 31 August this year. What's new compared tothe drafted guideline, we commented about on 23 August 2002. 

Quality of Drug Substance in the dossier for an application of amarketing authorisation

Since 01 July 2003 the harmonised format of the CTD (Common TechnicalDocument) is mandatory in the EU for all types of marketing authorisationsirrespective of procedure (national, Mutual Recognition Procedure orcentralised) or whether they are based on a full or abridged applicaton.
The CTD is an internationally agreed upon format for the preparation ofa presentation for applications to be submitted to the regulatoryauthorities.

The CTD is organized into 5 modules. Chemical, pharmaceutical andbiological documentation is provided by Module 3, the 'Quality Part' thatis subdivided into the drug substance ('S') and the drug product ('P')part.

According to the revised Guideline on Summary of Requirements forActive Substances in the Quality Part of the Dossier (CHMP/QWP/297/97Rev 1 corr - EMEA/CVMP/1069/02) that will be coming into operation on 01February 2005, there are 4 feasible ways to submit the requiredinformation for the drug substance:
2.1 Certificate of Suitability to the Monograph of the EuropeanPharmacopoeia
2.2 Active Substance Master File (ASMF) Procedure
2.3 Full details of manufacture
2.4 Other supportive data in consideration of the qualification ofimpurities

Details about the CEP procedures are laid down in Resolution AP-CSP(99) 4. The revised Guideline on Active Substance Master File Procedure(EMEA/CVMP/134/02 - CPMP/QWP/227/02) that is coming into operation on31 August this year is intended to help applicants for human andveterinary medicinal products, when using the European Drug Master File(EDMF) procedure for active substances in the preparation of a dossier foran application to a marketing authorisation.

Adopted Note for Guidance on the European Drug Master File Procedure

The draft revision of the NfG on the European Drug Master FileProcedure (EMEA/CVMP/134-02-CPMP/QWP/227/02-Consultation, February 2002)proposed to make the CEP procedure mandatory for those existing activesubstances described in the European Pharmacopoeia. This proposal was notagreed upon in the adopted version, where the EDMF procedures can still beused for all active substances, i.e.:

  • New active substances
  • Existing active substances not included in the EuropeanPharmacopoeia (Ph.Eur.) or the pharmacopoeia of an EU Member State
  • Pharmacopoeial active substances included in the Ph.Eur. or in thepharmacopoeia of an EU Member State

Additionally, the adopted version clarifies the cases where the EDMFholder may have an EDMF as well as a CEP for a single substance: "(…)Generally, it is however not acceptable that the Applicant/MA holderrefers to an EDMF as well as to a CEP for a single active substance of aparticular MAA. In cases where the CEP contains too little information(e.g. stability) the Competent Authorities/EMEA may decide that additionalinformation should be provided in the dossier. In such case it may beacceptable to refer both to an EDMF and a CEP (…)"


  • CEP = Certificate of Suitability to the Monograph of the EuropeanPharmacopoeia
  • EDMF = European Drug Master File
  • MAA = Marketing Authorisation Application

Dr Barbara Jentges

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