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Is an application for authorisation of an "integrated" protocol, which combines several parts possible at the BfArM? Date: 02. December 2008 Topics: Licensing Type: FAQ

In accordance with Directive 2001/20/EC, the principle "Each clinical trial must have a primary question" must be observed in clinical trials. In this context, a clinical trial may include several parts, provided the principle of a single …

What shall be submitted as a plan for further treatment? Date: 02. December 2008 Topics: Licensing Type: FAQ

In this context, applicants should describe which medical treatment the trial subjects will receive after completion of the clinical trial. Normally, patients will continue to receive their standard therapy or they will continue to be treated …

Which documents will be validated by the Subunit 'Clinical Pharmacology'? Date: 02. December 2008 Topics: Licensing Type: FAQ

In the formal validation, the Subunit 'Clinical Pharmacology' inspects the application form “Request for Authorisation” (parts E and F) with regard to mistakes or inconsistencies. Furthermore, the following documents are examined with respect to the …

What needs to be considered in paediatric trials? Date: 02. December 2008 Topics: Licensing Type: FAQ

The German Medicines Act (Arzneimittelgesetz, AMG) stipulates special safety provisions for minors participating in clinical trials. For all minors the provisions of § 40 AMG Section 40 sub-section 4 of the AMG apply; in addition, for minors …

Do special documents have to be submitted for paediatric trials? Date: 02. December 2008 Topics: Licensing Type: FAQ

Pursuant to Section 40 sub-section 4 number 2 of the German Medicines Act (Arzneimittelgesetz, AMG), a paediatric trial may only be conducted if clinical trials performed on adults or other research methods cannot be expected to produce satisfactory …

How often are paediatric trials currently submitted for authorisation at the BfArM? Date: 02. December 2008 Topics: Licensing Type: FAQ

Currently, approximately 6 % of all clinical trials conducted in Germany and approved by the BfArM are paediatric trials. Most often, clinical trials on minors are conducted in the fields neurology and psychiatry, respiratory tract, and …

Which objections regarding the trial protocol are the most frequent content-related objections in authorisation procedures? Date: 02. December 2008 Topics: Licensing Type: FAQ

Which objections regarding the trial protocol are the most frequent content-related objections in authorisation procedures?

  • The most frequent content-related objections regarding the trial protocol are:

  • inadequate risk-benefit …

Should a separate protocol be prepared for an extension phase of a clinical trial in which all subjects will receive verum or should the extension phase be submitted as an amendment to the protocol already authorised? Date: 02. December 2008 Topics: Licensing Type: FAQ

Whether the extension “treatment” is an amendment to the protocol or whether it is considered an “open-label extension study” depends on the objective and on the design of the previous study.

  • If the primary and secondary objectives …

How often shall the Investigator’s Brochure be updated? Date: 02. December 2008 Topics: Licensing Type: FAQ

Pursuant to Directive 2005/28/EC of the Commission dated 8 April 2005 Article 8 (3), the sponsor shall validate and update the Investigator’s Brochure, if necessary, at least once a year. If an update of the Investigator’s Brochure is not considered …

Which requirements should a trial protocol fulfil from the BfArM's point of view? Date: 02. December 2008 Topics: Licensing Type: FAQ

The trial protocol should contain information regarding the following issues, in compliance with the Guideline for Good Clinical Practice (CPMP/ICH/135/95), Chapter 6. Clinical trial protocol and protocol amendment(s):

  • table of …

What are the requirements for first-in-man clinical trials from a clinical point of view? Date: 02. December 2008 Topics: Licensing Type: FAQ

The trial protocol of first-in-man clinical trials involving a novel substance should include a critical discussion of whether the new investigational medicinal product is a potential high-risk medicinal product. The draft GUIDELINE ON REQUIREMENTS …

What is meant by "justification for sex distribution"? Date: 02. December 2008 Topics: Licensing Type: FAQ

In this context, applicants can specify that in the course of data analysis, stratification according to sex will be performed. If no sex-specific differences are meant to be investigated within the clinical trial, there should be an …

Which documents are to be submitted as a final clinical trial report? Date: 02. December 2008 Topics: Licensing Type: FAQ

It is not necessary to submit the entire final clinical trial report; submission of the trial synopsis is sufficient. A paper version of the trial synopsis is to be submitted, however, additional electronic submission would be greatly …

How long is the sponsor obliged to keep the documents of a clinical trial? Date: 02. December 2008 Topics: Licensing Type: FAQ

In accordance with Section 13 sub-section 10 of the GCP Ordinance, the sponsor shall ensure that the important documents of the clinical trial, including the protocol, are kept for at least ten years after the end or termination of the trial. …

Does the final clinical trial report have to be submitted to the national competent authority? Date: 02. December 2008 Topics: Licensing Type: FAQ

In accordance with Section 13 sub-section 9 of the GCP Ordinance (GCP-Verordnung), a summary of the clinical trial report shall be submitted to the national competent authority within a year after the end of the trial, covering all important …

Does the final clinical trial report have to be submitted one year after completion of the clinical trial in Germany or one year after completion of the trial worldwide? Date: 02. December 2008 Topics: Licensing Type: FAQ

Since a final clinical trial report can only be prepared after worldwide completion of the trial, the one-year period is calculated starting from the actual date of trial completion.

What needs to be considered in paediatric trials? Date: 02. December 2008 Topics: Licensing Type: FAQ

The cover letter shall state that it is intended to include minors in the clinical trial. We recommend describing as early as in the cover letter, how the following regulations will be implemented:

Pursuant to Section 40 sub-section 4 …

Is it possible to omit preclinical data in the IMPD? Date: 25. November 2008 Topics: Licensing Type: FAQ

Yes, in a simplified submission the preclinical section in the IMPD can refer to the corresponding IB section. In this case the IMPD layout should be used (see 15.). On the other hand, please keep in mind that the preclinical section in the IB

When should the applied doses in preclinical studies be declared in mg/kg as well as in mg/m2? Date: 25. November 2008 Topics: Licensing Type: FAQ

This is necessary if the dose for the use in humans is also declared in mg/m2 body surface.

Which guidelines in general are important for preclinical safety testing and documentation (IB, IMPD)? Date: 25. November 2008 Topics: Licensing Type: FAQ

The following guidelines are at minimum to consider (list is not complete):

  • ICH M3(M): CPMP/ICH/286/95

  • ICH S6: (Biotechnology) CPMP/ICH/302/95

  • ICH S7A: (Safetypharmacology) CPMP/ICH/539/00

  • ICH S7B (QT …