Notices to applicants

The Rules Governing Medicinal Products in the European Union, Volume 2, Notice to Applicants, Medicinal Products for Human Use. http //ec.europa.eu/enterprise/pharmaceuticals/index en.htm. 

The procedures and timelines for obtaining marketing authorisations for veterinary products are essentially the same as those for human medicines. Extensive guidance can be found in The Rules Governing Medicinal Products in the European Union, Volume 6 - Notice to Applicants, Veterinary Medicinal Products. The products that may follow centralised procedures and receive Community authorisations are shown in Eigure 7.5. All other products must obtain authorisations from national... 

Three volumes of information on the format and content of applications for marketing authorization and relevant regulatory guidelines have been prepared by the Commission (Enterprise Directorate General) and published as the Notice to Applicants. These volumes do not have legal force, but applications that fail to follow their prescriptions can be returned to applicants as invalid. 

Volume 2A Notice to applicants—Medicinal products for human use—Procedures for marketing authorisation Volume 2B Notice to applicants—Medicinal products for human use—Presentation and content of the dossier Volume 2C Notice to applicants—Medicinal products for human use—Regulatory guidelines Commission of the European Communities, Luxembourg, 1998/1998/ 1999 (and amendments)... 

The suggested headings and arrangement of the document may be found in The Rules Governing Medicinal Products in the European Union Volume 2, Notice to Applicants Volume 2B Presentation and Content of the Dossier, Common Technical Document which can be accessed at the Commission website www.pharmacos.eudra.org. Information is also available at the European Medicines Agency website www.emea.eu.int. 

The only other reference at a European level appears in Volume 9 (Pharmacovigilance) of the Notice to Applicants issued by the European Commission. The Notice to Applicants does not have the force of law, but represents best practise. Paragraph 1.3.4 states ... 

Volume 1 Pharmaceutical Legislation Volume 2 Notice to Applicants... 

From 1975 onward, however, the EU has requested experimental validation studies for a manufacturing process to be included in the application dossier where a nonstandard method is being used or where it is critical for the product (Council Directive 75/319/EEC [36] as amended by 91/356/EEC [37]). This requirement is amplified in the Notice to Applicants [38]. 

Medical products for human use, presentation and contents of the dossier. 1998. The rules governing medicinal products in the European Union Notice to Applicants. Luxembourg Office for Official Publications of the European Communities 2B. 

Notice to Applicants (Part III F Jan. 1989) Pharmacodynamics Studies conducted to establish the pharmacodynamis effects and the mode of action should be evaluated in the following order ... 

Notice to applicants for market authorization for veterinary medicinal products (1989, revised edition 1993) Establishment by the European community of maximum residue limits (MRLs) for residues of veterinary medicinal products in foodstuffs of animal origin (1991)... 

An applicant for a Product Authorisation should supply a dossier as set out in The Rules Governing Medicinal Products in Europe Volume II-Notice to Applicants. This sets out in detail what the required elements of the dossier are. 

The application format is to be harmonised with the EU Notice to Applicants (Expert Reports will also be requested). The particulars cind documents accompanying an application for marketing authorisation (MA) must be presented in four parts ... 

Figure 34.3 provides a flowchart and timelines for the MRP (see also Vol. 2A of the Notice to applicants Procedures for Marketing Authorisation... 

In all cases, the appropriate fees for the national applications must be paid and all necessary translations provided, at the time of the MRP submission. Chapter 7 of the Notice to Applicants provides, for each MS, the administrative details such as number of hard copies of the dossier, specified languages, samples of active substance and finished product, electronic formats and so on. 

To start a referral procedure different forms must be used, according to the type of referral such forms are annexed to the Guideline included in the Notice to Applicant Volume 2A - Procedures for Marketing Authorization - Chapter 3 - Community Referral - February 2004. 

Frequently, MA holders find it difficult to classify the requested labeling change into Type IA, IB and so on. The Notice to applicants of the EU Commission - Guideline on the categorisation of new applications versus variations applications, Jan 2002 aims to clarify these issues, and it has now been supplemented (July 2003) by the Guidance on dossier requirements for Type I A and IB notifications which lists of all foreseen variations, their classification and the documentation required. Revisions of the former are expected in late 2005. 

The assessment of safety in the use of medicinal products starts before the first administration to humans and continues throughout the development of the medicine to the MA for the lifetime of the drug. It is governed by a set of comprehensive rules, which are published in Volume 9 of the rules governing the use of medicinal products in the EU, notice to applicants (see boxed item above). These rules have seen several major updates in the time since the first publication in 1986, and a comprehensive review is currently ongoing. The nonclinical aspects of product safety are discussed elsewhere in this book. 

The European Commission. Notice to applicants, a guideline on Summary of product characteristics, December 1999 (included in the rules governing medicinal products in the European Community Vol. 2A and 2B). 

Notice to applicants of the EU Commission - guideline on the categorisation of new applications versus variations applications Jan 2002 (currently under revision to reflect the new regulations in force since Oct 2003). 

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