In order to speed up the processing of the applications at validation the following current requirements for submission should be taken into account.

Biowaiver: table of contents concerning Module 1 / Point 9

Documents concerning the bioavailability generally have to be submitted along with the application for marketing authorisation as a constant requirement.
If no comparative in vivo studies concerning the bioavailability / bioequivalence are being presented, significant documents, which substantiate the waiver for in vivo studies, have to be submitted as additional annexes to the application for marketing authorisation in duplicate, combined and stapled separately.

Power of Attorney / Point 2.4.2

If another person than the one stated in point 2.4.1 of the application form is appointed for communication during the procedure, a power of attorney has to be added as Annex 6.4 to the application.

Manufacturer / Point 2.5.2

A valid manufacturing license of the companies involved in the manufacture has to be submitted pursuant to Sections 13 and 16 AMG. If this is not available in German or English, a translation drawn up by a publicly appointed or certified interpreter or translator has to be presented additionally.

Import License

Pursuant to Section 22 sub-section 5 AMG, evidence has to be provided within the authorisation procedure that the manufacturer is authorised to manufacture medicinal products according to the regulations of the country of production, if the manufacturing of the medicinal product (finished drug or bulk) takes place in countries which are not Member States of the European Union or contractual states of the convention of the European Economic Area. Additionally, an import license for the importer has to be presented pursuant to Section 72 AMG.A so-called MRA-agreement does not pose an exemption from the obligation to submit an import license.

The import license is to be applied for from the EU Member State/State of the EEA to which the medicinal products are to be imported.

The import license has to be presented. If applicable, a translation into German or English drawn up by a publicly appointed or certified interpreter or translator has to be presented.

Should delays occur in the provision of the import license, a written confirmation of the competent authority has to be presented stating that an import license has been applied for.

However, in accordance with Section 72 AMG (cf. Section 22 sub-section 5 AMG), a import license as to be handed in before finalising the procedure, because a missing import license may result in the rejection of an application for marketing authorisation pursuant to Section 25 sub-section 2 No. 1 AMG.

EDMF/ ASMF / Point 2.5.3

In case participation in a European Drug Master File (EDMF) procedure is intended, a declaration of the applicant concerning the European Drug Master File procedure has to be presented stating the name of the active substance, the EDMF number as well as the national procedure number.

A form to be filled in electronically is available on the BfArM Homepage.

Furthermore, it has to be ensured that the documents which have to be submitted directly by the manufacturer of the substance are being presented in accordance with the announcement stated below:

• The restricted part and the applicant´s part of the EDMF / ASMF
• The letter of access including statement of the present applicant
• The Quality Overall Summary concerning the restricted part of the EDMF / ASMF

Certificate of Suitability (CEP)/ Point 2.5.3

If it is stated in the application that a certificate of the European Pharmacopoeia exists (Ph. Eur. Certificate of Suitability) for the substance, a copy of this certificate (CEP) is to be presented.

Module 1.4

The signed declarations of the experts concerning the submitted expert reports and the curriculae vitae (details regarding the scientific and professional backgrounds of the experts) have to be submitted in module 1.4 pursuant to Directive 2003/63/ EG amending Annex I of Directive 2001/83/ EG.

14^th Amendment of the German Medicines Act

Additionally, the following documents are to be submitted since the coming into force of the 14^th Amendment of the German Medicines Act pursuant to Section 22 AMG:

• Declaration on clinical trials which were conducted outside the EU (cf. Section 22 sub-section 2 no. 4 AMG), Module 1.9
• Characterisation of the pharmacovigilance system and, if applicable, of the intended risk management system(cf. Section 22 sub-section 2 no. 5 AMG) Module 1.8
• Verification of the qualified person pursuant to Section 63a AMG(cf. Section 22 sub-section 2 no. 6 AMG)
• Copy of any designation of the medicinal product as an orphan medicinal product
  (cf. Section 22 sub-section 2 no. 7 AMG) Module 1.7
• Documents regarding potential environmental risks (cf. Section 22 sub-section 3c AMG) Module 1.6
• Results of the evaluation of the Package Leaflet / "User testing“(cf. Section 22 sub-section 7 AMG) Module 1.3.4

In any case, a detailed justification has to be given in case the presentation of individual documents is deemed unnecessary.

AMG Submission Ordinance

On 1 January 2001, the "Ordinance on the Submission of Documents within Licensing and Renewal Procedures (AMG Submission Ordinance – AMG-EV)“ of 21 December 2000(Federal Law Gazette Part I No. 60 of 29 December 2000, page 2036) came into force. All documents mentioned in Section 2 sub-section 1 AMG-EV, e.g. the draft labelling pursuant to Section 10 AMG, the Package Leaflet pursuant to Section 11 AMG, the SPC pursuant to Section 11a AMG and the expert reports pursuant to Section 24 sub-section 1 no. 1-3 AMG (Modules 2.2, 2.3, 2.4. 2.5, 2.6 and 2.7), have to be submitted electronically by e-Mail to the address: zulassung@amg-zulassung.de. The documents pursuant to Sections 10, 11 and 11a AMG as well as the expert reports pursuant to Section 24 AMG have to be submitted electronically each as separate files in Rich Text Format (rtf), as described under point 4.3.2 of the explanations given below (e.g. no summing-up of the draft labelling and draft Package Leaflet and SPC pursuant to Sections 10, 11 and 11a AMG in one file).

However, it is possible to exclusively submit Module 2.3 as a pdf file. The pdf file must not be blocked or contain scanned documents.

Combination Argument

If a medicinal product contains more than one active substance, a reason for this combination pursuant to Section 22 sub-section 3a AMG has to be submitted which proves that each active substance contributes to a positive assessment of the medicinal product.

If such a combination argument is missing, this may lead to the rejection of the application for marketing authorisation pursuant to Section 25 sub-section 2 no. 1 AMG.

Sources

• Guide to submission of applications for marketing authorisations at the Federal Institute for Drugs and Medical Devices on the BfArM Homepage under http://www.bfarm.de
• "Explanatory notes concerning applications for marketing authorisation of medicinal products", 3^rd edition, of 31 October 1996 (German Federal Gazette, Volume 49 of 5 March 1997 No. 44a) – as far as still applicable with regard to contents
• Guide to submission of applications for marketing authorisations in CTD format to the Federal Institute for Drugs and Medical Devices on the BfArM Homepage under http://www.bfarm.de
• Ordinance on the Submission of Documents within Licensing and Renewal Procedures (AMG Submission Ordinance – AMG-EV)“ of 21 December 2000 (Federal Law Gazette Part I No. 60 of 29 December 2000, page 2036) and explanatory notes on the execution of the AMG Submission Ordinance – Version 4.09 of 1 August 2004 on the BfArM Homepage under http://www.bfarm.de
• 2nd Announcement concerning the European Drug Master File procedure of 9 June 1995 (German Federal Gazette No. 126 of 8 July 1995, page 7389)
• 3rd Announcement concerning the European Drug Master File procedure of 25 April 1997 (German Federal Gazette No. 92 of 22 May 1997, page 6226)
• Guideline on Active Substance Master File Procedure (CPMP /QWP/227/02 Rev 1; EMEA/CVMP /134/02 Rev 1, April 2005)
• Announcement concerning the authorisation pursuant to Section 21 AMG (Bioavailability / Bioequivalence) of 18 December 2002 (German Federal Gazette of 25 March 2003, page 5296)
• Note for Guidance on the Investigation of Bioavailability and Bioequivalence (CPMP/EWP/QWP/1401/98, July 2001)
• Directive 2004/27/ EC of the European Parliament and the Council of 31 March 2004 amending the Directive 2001/83/EG on the Community code relating to the medicinal products for human use
• Directive 2003/63/ EC of the Commission of 25 June 2003 amending the Directive 2001/83/EC of the European Parliament and the Council on the Community code relating to the medicinal products for human use
• Notice to Applicants, Volume 2A, Chapter 1 (November 2005) and Chapter 7 (March 2006), Volume 2B - Common Technical Document (CTD) (June 2006)