What changed between the plenary report and the adopted text

Added:The name and address of the applicant shall be given, together with the name and address of the manufacturers and the sites involved in the different stages of the manufacture (including the manufacturer of the finished product and the manufacturer(s) of the active substance(s)), and where relevant the name and address of the importer.

Added:The applicant shall identify the type of application and indicate what samples, if any, are also provided.

Added:Annexed to the administrative data shall be copies of the manufacturing authorisation as defined in Article 40, together with a list of countries in which authorisation has been granted, copies of all the summaries of product characteristics in accordance with Article 11 as approved by Member States and a list of countries in which an application has been submitted.

Added:As outlined in the application form, the applicants shall provide, inter alia, details of the medicinal product subject of the application, the legal basis of the application, the proposed marketing authorisation holder and manufacture(s), information on orphan medicinal product status, scientific advice and paediatric development program.

Added:1.3. Summary of product characteristics, labelling and package leaflet

Added:1.3.1. Summary of product characteristics

Added:The applicant shall propose a summary of the product characteristics, in accordance with Article 11.

Added:1.3.2. Labelling and package leaflet

Added:A proposed labelling text for immediate and outer packaging as well as for the package leaflet shall be provided. These shall be in accordance with all mandatory items listed in Title V on the labelling of medicinal products for human use (Article 63) and on package leaflet (Article 59).

Added:1.3.3. Mock-ups and specimens

Added:The applicant shall provide specimen and/or mock-ups of the immediate and outer packaging, labels and package leaflets for the medicinal product concerned.

Added:1.3.4. Summaries of product characteristics already approved in the Member States

Added:Annexed to the administrative data of the application form shall be copies of all the summaries of product characteristics in accordance with Articles 11 and 21 as approved by Member States, where applicable and a list of countries in which an application has been submitted.

Added:1.4. Information about the experts

Added:In accordance with Article 12 (2) experts must provide detailed reports of their observations on the documents and particulars which constitute the marketing authorisation dossier and in particular on Modules 3, 4 and 5 (chemical, pharmaceutical and biological documentation, non-clinical documentation and clinical documentation, respectively). The experts are required to address the critical points related to the quality of the medicinal product and of the investigations carried out on animals and human beings and bring out all the data relevant for evaluation.

Added:These requirements shall be met by providing a quality overall summary, a non-clinical overview (data from studies carried out in animals) and a clinical overview that shall be located in Module 2 of the marketing authorisation application dossier. A declaration signed by the experts together with brief information on their educational background, training and occupational experience shall be presented in Module 1. The experts shall have suitable technical or professional qualifications. The professional relationship of the expert to the applicant shall be declared.

Added:1.5. Specific requirements for different types of applications

Added:Specific requirements for different types of applications are addressed in Part II of the present Annex.

Added:1.6. Environmental risk assessment

Added:Where applicable, applications for marketing authorisations shall include a risk assessment overview evaluating possible risks to the environment due to the use and/or disposal of the medicinal product and make proposals for appropriate labelling provisions. Environmental risk connected with the release of medicinal products containing or consisting of GMOs (Genetically Modified Organisms) within the meaning of Article 2 of Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of modified organisms and repealing Council Directive 90/220/EEC () shall be addressed.

Added:Information pertaining to the environmental risk shall appear as an appendix to Module 1.

Added:The information shall be presented in accordance with the provisions of Directive 2001/18/EC, taking into account any guidance documents published by the Commission in connection with the implementation of the said Directive.

Added:The information shall consist of:

Added:— an introduction;

Added:— a copy of any written consent or consents to the deliberate release into the environment of the GMO(s) for research and development purposes according to Part B of Directive 2001/18/EC;

Added:— the information requested in Annexes II to IV of the Directive 2001/18/EC, including detection and identification methods as well as unique code of the GMO, plus any additional information on the GMO or the product of relevance to evaluating the environmental risk;

Added:— an environment risk assessment (ERA) report prepared on basis of the information specified in Annexes III and IV of Directive 2001/18/EC and in accordance with Annex II of Directive 2001/18/EC;

Added:— taking into account the above information and the ERA, a conclusion which proposes an appropriate risk management strategy which includes, as relevant to the GMO and product in question, a post-market monitoring plan and the identification of any special particulars which need to appear in the Summary of Product Characteristics, labelling and package leaflet;

Added:— appropriate measures in order to inform the public.

Added:A dated signature of the author, information on the author's educational, training and occupational experience, and a statement of the author's relationship with the applicant, shall be included.

Added:2. MODULE 2: SUMMARIES

Added:This Module aims to summarise the chemical, pharmaceutical and biological data, the non-clinical data and the clinical data presented in Modules 3, 4 and 5 of the dossier for marketing authorisation, and to provide the reports/overviews described in Article 12 of this Directive.

Added:Critical points shall be addressed and analysed. Factual summaries including tabular formats shall be provided. Those reports shall provide cross-references to tabular formats or to the information contained in the main documentation presented in Module 3 (chemical, pharmaceutical and biological documentation), Module 4 (non-clinical documentation) and Module 5 (clinical documentation).

Added:Information contained in Module 2 shall be presented in accordance with the format, content and numbering system delineated in the Volume 2 of the Notice to Applicants. The overviews and summaries shall comply with the basic principles and requirements as laid down herewith:

Added:2.1. Overall table of contents

Added:Module 2 shall contain a table of contents for the scientific documentation submitted in Modules 2 to 5.

Added:2.2. Introduction

Added:Information on the pharmacological class, mode of action and proposed clinical use of the medicinal product for which a marketing authorisation is requested shall be supplied.

Added:2.3. Quality overall summary

Added:A review of the information related to the chemical, pharmaceutical and biological data shall be provided in a quality overall summary.

Added:Key critical parameters and issues related to quality aspects shall be emphasised as well as justification in cases where the relevant guidelines are not followed. This document shall follow the scope and outline of the corresponding detailed data presented in Module 3.

Added:2.4. Non-clinical overview

Added:An integrated and critical assessment of the non-clinical evaluation of the medicinal product in animals/in vitro shall be required. Discussion and justification of the testing strategy and of deviation from the relevant guidelines shall be included.

Added:Except for biological medicinal products, an assessment of the impurities and degradation products shall be included along with their potential pharmacological and toxicological effects. The implications of any differences in the chirality, chemical form, and impurity profile between the compound used in the non-clinical studies and the product to be marketed shall be discussed.

Added:For biological medicinal products, comparability of material used in non-clinical studies, clinical studies, and the medicinal product for marketing shall be assessed.

Added:Any novel excipient shall be the subject of a specific safety assessment.

Added:The characteristics of the medicinal product, as demonstrated by the non-clinical studies shall be defined and the implications of the findings for the safety of the medicinal product for the intended clinical use in human shall be discussed.

Added:2.5. Clinical overview

Added:The clinical overview is intended to provide a critical analysis of the clinical data included in the clinical summary and Module 5. The approach to the clinical development of the medicinal product, including critical study design, decisions related to and performance of the studies shall be provided.

Added:A brief overview of the clinical findings, including important limitations as well as an evaluation of benefits and risks based on the conclusions of the clinical studies shall be provided. An interpretation of the way the efficacy and safety findings support the proposed dose and target indications and an evaluation of how the summary of product characteristics and other approaches will optimise the benefits and manage the risks is required.

Added:Efficacy or safety issues encountered in development and unresolved issues shall be explained.

Added:2.6. Non-clinical summary

Added:The results of pharmacology, pharmaco-kinetics and toxicology studies carried out in animals/in vitro shall be provided as factual written and tabulated summaries which shall be presented in the following order:

Added:— Introduction

Added:— Pharmacology Written Summary

Added:— Pharmacology Tabulated Summary

Added:— Pharmaco-kinetics Written Summary

Added:— Pharmaco-kinetics Tabulated Summary

Added:— Toxicology Written Summary

Added:— Toxicology Tabulated Summary.