Introduction

With the entry into force of the Act for the Restructuring of the Pharmaceutical Market in Statutory Health Insurance ("Arzneimittelmarktneuordnungsgesetz", AMNOG) on 1 January 2011, Section 42b – Publication of the results of clinical trials was added to the sixth chapter of the German Medicinal Products Act (AMG).

Section 42b AMG refers to the provision of result reports of clinical trials with licensed medicinal products for publication by the higher federal authorities. While the obligations stated in sub-section 1 refer to pharmaceutical entrepreneurs who place a medicinal product subject to the obligation to have a marketing authorisation on the German market the obligations in sub-section 2 are aimed at the sponsors of clinical trials performing clinical trials with a licensed medicinal product with at least one trial centre in Germany.

Obligations of pharmaceutical entrepreneurs

In accordance with Section 42b sub-section 1 AMG, pharmaceutical entrepreneurs who place a medicinal product, which is subject to the obligation to have a marketing authorisation/centralised marketing authorisation and intended for use in humans, on the market within the scope of the AMG are obligated to place reports on all the results of confirmatory clinical trials substantiating the efficacy and safety of the medicinal product at the disposal of the competent higher federal authority. These reports shall be made available within six months subsequent to the granting of the marketing authorisation/centralised marketing authorisation. This obligation applies regardless of whether one or several of the trial sites used were located in Germany, i.e. even when the clinical trial was entirely conducted abroad.

Obligations of the sponsors of clinical trials

In accordance with Section 42b sub-section 2 AMG, sponsors of clinical trials with a medicinal product which has already been granted a marketing authorisation/centralised marketing authorisation as the investigational product and with at least one trial centre in Germany are obligated to make the results of the clinical trial available within one year after its completion pursuant to Section 42b sub-section 1, regardless of whether the clinical trial was performed for the purpose of a change of marketing authorisation or not.

Requirements with regard to contents

The manner in which these reports are to be submitted is specified in Section 42b sub-section 3 AMG. Pursuant to this, the reports written in German or English must contain all of the results of the clinical trials, regardless of whether they are favourable or not. The reports also must include information regarding subsequent essential modifications to the trial protocol as well as interruptions and early terminations of the clinical trial.

Retroactivity

The relevant transitional regulations pursuant to Section 145 AMG are applicable for medicinal products granted a marketing authorisation/centralised marketing authorisation prior to 1 January 2011. This section specifies that result reports have to be submitted by 1 July 2012 for all medicinal products already licensed on 1 January 2011 or for clinical trials with licensed medicinal products completed by 1 January 2011 under the condition that these clinical trials were subject to authorisation by the competent higher federal authority as of 6 August 2004, i.e. the authorisation of the clinical trial had been requested in Germany.

Exception: generically licensed medicinal products

In accordance with chapter 4 of the "Announcement regarding the publication of the results of clinical trials in accordance with Section 42b AMG" of 3 August 2011 (see below) no result reports have to be submitted for generically licensed medicinal products for which no confirmatory studies but only bioequivalence studies were submitted for licensing. Instead, reference to the originator product is to be made via the web portal for Section 42b AMG in the PharmNet.Bund system.

Format of result reports

The result reports in accordance with Section 42b AMG are to be presented in the format of the synopsis described in ICH Topic E 3 - Note for Guidance on Structure and Content of Clinical Study Reports. The following table lists the minimum requirements for this synopsis:

Minimum information required for a synopsis in accordance with ICH E3

1) Name of Sponsor/Company	12) Methodology
2) Name of Finished Product	13) Number of patients (planned and analysed)
3) Name of Active Substance	14) Diagnosis and main criteria for inclusion
4) Individual Study Table: Referring to Part of the Dossier (Volume, Page) Note: This information is only required for submissions in connection with a licensing dossier	15) Test product, dose and mode of administration, batch number
5) Title of Study Note: It must be made clear that the last version of the protocol including all amendments is meant; the amendments are to be listed and identified	16) Duration of treatment
6) Investigators	17) Reference therapy, dose and mode of administration, batch number
7) Study centre(s)	18) Criteria for evaluation: Efficacy, Safety
8) Publication (reference)	19) Statistical methods
9) Studied period (years): date of first enrolment, date of last completed Note: Study interruptions and premature/early terminations are also to be listed here together with the reasons therefore	20) Summary – Conclusions: Efficacy Results, Safety Results, Conclusion
10) Phase of development	21) Date of report
11) Objectives

For further details please consult the "Announcement regarding the publication of the results of clinical trials in accordance with Section 42b of the AMG" of 3 August 2011 (published in the Federal Gazette no. 127 of 24 August 2011, p. 2975) as well as the Frequently Asked Questions on this subject:

FAQs regarding Section 42b AMG (currently only available in German)

Submission of result reports using the web portal

The announcement of 3 August 2011 provides for electronic submission of the reports. For this purpose, a web-based portal for submissions has been created on the internet pages of the PharmNet.Bund portal. The report itself must be available as a PDF file and is then transmitted to the competent higher federal authority by uploading it to the web portal. The web portal in PharmNet.Bund can be reached by clicking the following link:

• Web portal for electronic submission of result reports in accordance with Section 42b AMG (PharmNet.Bund)
• Manual for the web portal (currently only available in German)

Publication of result reports

The competent higher federal authority evaluates the statements made in the synopsis (and attached data/documents) and, if necessary, requests and assesses additional information. A reference is added to the result reports on clinical trials stating that these are the data of the pharmaceutical entrepreneur or sponsor. They are published under the PharmNet.Bund system and as soon as the portal is activated, a corresponding link will be posted here.

Further information

• FAQs regarding Section 42b AMG (in German language)
• Section 42b AMG
• Section 145 AMG
• ICH Topic E 3 - Note for Guidance on Structure and Content of Clinical Study Reports