EU Module 1 Requirements

EU Module - 1 CTD Requirements 

EU Regional Requirements or Module 1 EU CTD: This module contains the specific EU-requirements for the administrative data (e.g. the application form, the proposed summary of product characteristics, labelling and package leaflet, etc.). 

EU Module 1 CTD consists 10 sections.

1.0 Cover Letter:  MA Holder has to provide the separate cover letter for each member state. 

Ex: In DCP, RMS - Germany (DE),  CMS - Sweden (SE), Ireland (IE), Netherlands (NL)

MA holder has to provide the cover letters as follows:

de-cover

se-cover

ie-cover

nl-cover

1.1 Comprehensive Table of Contents: ToC of Module1 to Module 5  as per the ICH CTD (granularity)

1.2  Application Form: It contains---

• Declaration and signature of MA holder
• Type of application
• MAA particulars
• Annexes

Further information:

New Applications and Extension Applications

Variation applications

Renewal applications

Annexes (Where appropriate):

1. Proof of payment
2. Informed consent letter of marketing authorisation holder of authorised medicinal product.
3. Proof of establishment of the applicant in the EEA.
4. Letter of authorisation for communication on behalf of the applicant/MAH.
5. Curriculum Vitae of the Qualified Person for Pharmacovigilance.
6. Manufacturing Authorisation required under Article 40 of Directive 2001/83/EC (or equivalent, outside of the EEA where MRA or other Community arrangements apply); any proof of authorisation in accordance with Article 8(k) of Directive 2001/83/EC.
7. Copy of the ‘Qualification of SME Status’.
8. Flow-chart indicating all manufacturing and control sites involved in the manufacturing process of the medicinal product and the active substance.
9. GMP certificate(s) or other GMP statement(s); Where applicable a summary of other GMP inspections performed.
10. Letter(s) of access to Active Substance Master File(s) or copy of Ph. Eur. Certificate(s) of Suitability.
11. Copy of written confirmation from the manufacturer of the active substance to inform the applicant in case of modification of the manufacturing process or specifications according to Annex I of Directive 2001/83/EC.
12. Ph. Eur. Certificate(s) of suitability for TSE.
13. Written consent(s) of the competent authorities regarding GMO release in the environment.
14. Scientific Advice given by CHMP and/or by member state(s).
15. Copy of Marketing Authorization(s) required under Article 8(j)-(L) of Directive 2001/83/EC in the EEA and the equivalent in third countries on request (a photocopy of the pages which give the marketing authorization number, the date of authorisation and the page which has been signed by the authorizing competent authority will suffice).
16. Correspondence with European Commission regarding multiple applications.
17. List of Mock-ups or Samples/specimens sent with the application, as appropriate
18. Copy of the Orphan Designation Decision.
19. List of proposed (invented) names and marketing authorisation holders in the concerned member states.
20. Copy of EMEA certificate for a Vaccine Antigen Master File (VAMF).
21. Copy of EMEA certificate for a Plasma Master File (PMF).
22. For each active substance, attach a declaration(s) from the Qualified Person of the manufacturing authorisation holder in Section 2.5.1 and from the Qualified Person of each of the manufacturing authorisation holders (i.e. located in EEA) listed in Section 2.5.2 where the active substance is used as a starting material that the active substance is manufactured in compliance with the detailed guidelines on good manufacturing practice for starting materials.  Alternatively, such declaration may be signed by one Qualified Person on behalf of all QPs involved (provided this is clearly indicated). 

Further information: Data requested for New Applications in the MRP/DCP

1.3 Product Information: Applicants/marketing authorisation holders must include proposals for (revised) Summary of Product Characteristics (SPC), labelling and package leaflet in their application.

1.3.1SmPC, Labelling & PL: Content is defined in legislation: Dir 2001/83 as amended with 2004/27/EC

• SmPC: Listing of particulars which must appear in the SmPC,
• Label: Content is legally defined which must appear on the label
• Package leaflet: Listing of particulars which must appear in the Package Leaflet, order of PL is fixed

The national competent authorities and the EMEA have published templates in all EU languages  for the presentation of product information.

MRP/DCP Procedures: QRD annotated template

Centralized procedure: Annotated & Clean template

1.3.2 Mock-up:  A “mock-up” is a copy of the flat artwork design in full colour, providing a replica of both the outer and immediate packaging, providing a two-dimensional presentation of the packaging/labelling of the medicinal product. It is generally referred to as a “paper copy” or “computer generated version”.

1.3.3 Specimen: A “specimen” is a sample of the actual printed outer and immediate packaging materials and

package leaflet.Further information: Notice to Applicants, Vol. 2A, Chapter 7

1.3.4 Consultation with Target Patient Groups: Articles 59(3) and 61(1) of Directive 2001/83/EC require that the package leaflet reflects the results of consultations with target patient groups to ensure that it is legible, clear and easy to use, and that results of assessments carried out in cooperation with target patient groups be provided to the competent authority/EMEA.

Further information: Guideline on the readability of the label and package leaflet of medicinal products for human use

1.3.5 Product Information already approved in the Member States

1.3.6 Braille

1.4 Information about the Experts:

• The Quality Overall Summary, Non-clinical Overview / Summary and Clinical Overview / Summary in Module 2,
• A declaration signed by the experts in Module 1.4.
• A brief information on the educational background, training and occupational experience in Module 1.4.

1.5 Specific requirements for Different Types of Applications

1.5.1 Information for Bibliographical Applications: For bibliographical applications based upon Article 10a of Directive 2001/83/EC applicants should provide here a concise document (up to approximately 5 pages), summarizing the grounds and evidence used for demonstrating that the constituent(s) of the medicinal product have a well-established use, with an acceptable level of safety and efficacy.

1.5.2 Information for Generic, ‘Hybrid’ or Bio-similar Applications: For applications based upon Article 10(1), 10(3) or 10(4) of Directive 2001/83/EC, applicants should provide here a concise document (up to approximately 5 pages), summarizing the grounds and evidence used for demonstrating that the medicinal product for which an application is submitted, is:

• Generic Applications (Art 10.1) : Summary should include details on the medicinal product, its qualitative and quantitative composition in active substance(s), its pharmaceutical form and its safety/efficacy profile of the active substance(s) in comparison to the active substance(s) of the reference medicinal product, as well as details related to the bio-availability and bio-equivalence, where necessary, of the medicinal product concerned.
• Hybrid applications (Art 10.3): Summary should include details on the medicinal product, its active substance, pharmaceutical form, strengths, therapeutic indications, route of administration as appropriate in comparison to the reference medicinal product, as well as details related to the bio-availability and bio-equivalence, where necessary, of the medicinal product concerned.
• Bio-similar applications (Art 10.4): Summary should include details on the similar biological medicinal product, its active substance, raw materials and manufacturing process.

1.5.3 (Extended) Data / Market Exclusivity: This section is required in case the marketing authorisation holder/applicant wishes to claim (additional) data / market exclusivity when applying for a new indication or change in classification of drug.

1.5.4 Exceptional Circumstances: An authorisation may be granted in exceptional circumstances subject to a requirement for the applicant to introduce specific procedures, in particular concerning the safety of the medicinal product, notification to the competent authorities of any incident relating to its use, and action to be taken.

1.5.5 Conditional Marketing Authorisation: only applicable to applications in the centralised procedure.

1.6 Environmental Risk Assessment: Relate to those risks to the environment arising from use, storage and disposal of medicinal products and not for risks arising from the synthesis or manufacture of medicinal products.

1.6.1 Non-GMO: Applications for marketing authorisations for medicinal products which do not contain GMOs (Genetically Modified Organisms) should include in Module 1 an indication of any potential risks presented by the medicinal product for the environment.

Further information: Guideline on the Environmental Risk Assessment for medicinal products for human use

1.6.2 GMO: Applications for marketing authorisations for medicinal products which contain GMOs

(Genetically Modified Organisms) should include in Module 1 an environmental risk assessment.

1.7 Information relating to Orphan Market Exclusivity: Not applicable for generics

1.7.1 Similarity

1.7.2 Market Exclusivity

1.8 Information relating to Pharmacovigilance

1.8.1 Pharmacovigilance System: Applicant has to provide DDPS (Detailed description of the

pharmacovigilance system). This should include proof that the applicant has the services of a qualified person responsible for pharmacovigilance and the necessary means for the notification of any adverse reaction

occurring either in the Community or in a third country.

1.8.2 Risk-management System: Applicant has to provide the detailed description of a risk management system should be provided in the form of an EU Risk Management Plan (EU-RMP).

The EU-RMP contains 2 parts:

Part I

• A Safety Specification
• A Pharmacovigilance Plan, and

Part II

• An evaluation of the need for risk minimisation activities, and if there is a need for additional (ie non- routine) risk minimisation activities:
• A risk minimisation plan

Further information: Volume 9A of Eudralex

1.9 Information relating to Clinical Trials: This statement should indicate that “clinical trials carried out outside the European Union meet the ethical requirements of Directive 2001/20/EC” together with a listing of all trials (protocol number) and third countries involved.

1.10 Information relating to Paediatrics: Required for Paediatric Use marketing authorisation applications (PUMA)