Legal Basis of the Application
In Europe, the first step for any new registration is “what is the proposed legal basis of the application”. The legal basis will dictate the dossier content, market exclusivity, and paediatric requirements in a very profound way. Directive 2001/83/EC as amended outlines the various “legal basis” that a new application can adopt. It is also important to note that in Europe your legal basis is independent of the procedural route that your company wishes to take. Whether you decide the Centralised, Decentralised, or National route your choice in a legal basis will remain the same. In the majority of circumstances, only one legal basis will be appropriate whereby your product only fits into one category. But what happens when your product doesn’t fit nicely into one of the legal basis categories. You can be left navigating the depths of Directive 2001/83/EC and coming up with more questions than answers. When your product is an established active substance where there is no current patent but includes a new dosage form, strength, route of administration, a new indication, or any combination of these, your product cannot be considered as a generic medicine. Three possible legal bases may be open to you:- Article 8 (3) Full Dossier Mixed Marketing Authorisation
- Article 10 (a) Full Dossier Well established use
- Article 10 (3) Abbreviated Dossier (hybrid application)
Article 8 (3) Full Dossier Mixed Marketing Authorisation | Article 10 (a) Full Dossier Well Established Use | Article 10 (3) Abbreviated Dossier (hybrid application) | |
Dossier Requirements | · Company’s own studies + published peer-reviewed literature · No reliance on EU Reference product. · Paediatric regulation 1901/2006 is applicable · PIP/waiver must be submitted · Advantages due to certain data protection and market exclusivity | · Must demonstrate “well established use” of the active substance in the community over a 10 year period. This use must also demonstrate that the active substance has a recognised efficacy and an acceptable level of safety. · Proposed indication must be aligned with the existing recognised indication within the EU · Risk of rejection in certain member states if an alternative route of administration is proposed · No reliance on an EU reference product · Paediatric regulation 1901/2006 is not applicable · No PIP/waiver is required | · EU reference product is required and must be referenced in the dossier · Company’s own studies which must have been conducted using the EU reference product (i.e. bioequivalence) · Reference is made in the dossier to the Non-clinical and Clinical data of the EU reference product · Paediatric regulation 1901/2006 is not applicable · No PIP/waiver is required |
Module 1
Another area that can present problems for companies who are inexperienced in the EU regulatory process is Module 1. Module 1 is crucial to the successful validation of any procedure within Europe and requires time to compile and generate properly. It is important that you identify what documents you will require in Module 1 and that is largely based on your proposed legal basis. Documents that require planning at an early stage are outlined below.- Section 1.3.4 Consultation with Target Patient Groups (PIL User Testing)
- Section 1.6 Environmental Risk Assessment
- Section 1.8.1 Pharmacovigliance System
- Section 1.8.2 Risk Management System
- Section 1.10 Paediatrics (PIP/Waiver)
- Section 1.2 Application Form eAF
Module 2
Module 2 is generic across all the proposed legal basis and all documentation should be supplied as outlined in the eCTD guidelines.Module 3
While the large proportion of any Module 3 dossier is consistent no matter where the dossier is registered it is important to note the following points:- All non-EU references must be removed and replaced with the EU equivalent (e.g. USP to Ph.Eur.)
- Appropriate EU Guidance documents must be referred too throughout each document in module 3
- European specifications and associated limits as detailed in the various EMA guidance documents must be adhered to