Active Substance Master Files (ASMF)
Here you will find answers to frequently asked questions about ASMF.
Are separate documentations regarding the active substance (Active Substance Master Files [ASMF]) accepted in the course of authorisation procedures for clinical trials?
Yes, as a rule Active Substance Master Files [ASMF] are also accepted for chemically defined active substances in authorisation procedures for clinical trials.
However, as in the case of marketing authorisations for medicinal products, ASMF are not (!) accepted for biological active substances (cf. guideline CPMP/QWP/227/02 Rev 2 Consultation). Use of ASMF is also not possible for excipients or for investigational medicinal products themselves.
Can reference be made to ASMF that were already used for previous marketing authorisation procedures?
Yes, the BfArM collects ASMF in a central archive. Reference can be made to ASMF already used in marketing authorisation procedures.
Which parts does an ASMF for a clinical trial have to consist of?
ASMF used for a request for authorisation of a clinical trial must contain the documentation on manufacture and testing of the active substance to the same extent necessary for the evaluation of investigational medicinal products. Furthermore, a letter of access from the manufacturer of the active substance must be submitted which authorises the BfArM to access the documentation for processing of the corresponding request for authorisation of a clinical trial.
A Quality Overall Summary, as is necessary for applications for marketing authorisation does not (!) have to be included.
Does an ASMF for the authorisation procedure of a clinical trial have to contain a Quality Overall Summary?
No, as no Quality Overall Summaries have to be submitted in the course of authorisation procedures for clinical trials, an ASMF for a clinical trial does not have to contain a Quality Overall Summary.
However, an ASMF without a Quality Overall Summary cannot be considered in marketing authorisation procedures.
How should the documentation be submitted?
The ASMF should be submitted at least 2 weeks prior (!) to the request for authorisation of a clinical trial. The reference line of the cover letter should make clear that an ASMF is being submitted. The EudraCT number of the clinical trial for which the ASMF is being submitted is also to be stated in the letter.
Prior submission of the ASMF is necessary as authorisation procedures for clinical trials have very narrow deadlines and processing of a request can only start when all parts of the documentation (including ASMF) have been submitted.
In cases in which the ASMF has already been submitted to the BfArM, it is sufficient to submit the letter of access from the manufacturer of the active substance. The BfArM's ASMF number should also be stated.
The original letter of access from the manufacturer of the active substance should be submitted together with the request for authorisation of a clinical trial. A copy of this letter should be included in the ASMF.
The cover letter accompanying the request for authorisation of a clinical trial should contain a reference to the use of the ASMF.
What information is to be included in the request for authorisation of a clinical trial when referring to an ASMF?
In addition to submission of the letter of access from the manufacturer of the active substance, the cover letter accompanying the application should point out that reference is being made to an ASMF. This ensures prompt consolidation of the documents.
What happens if the ASMF is updated by the manufacturer of the active substance?
If the BfArM is supposed to consider an updated ASMF for an ongoing clinical trial, a substantial amendment must be applied for by the sponsor of the clinical trial concerned.
Please note that in connection with clinical trials only so-called substantial amendments are subject to approval. For classification of substantial and non-substantial amendments cf. section 8 of the "Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials (CHMP/QWP/185401/2004-final)".
Thus, submission of an updated ASMF by the manufacturer of the active substance does not (!) lead to its automatically being applied to all clinical trials originally referring to the ASMF.