FDA 1572 in Germany
Интересная новость из Германии. А подписывают ли наши исследователи FDA 1572 и соответствует ли это нашему законодательству?
There were a lot of questions regarding the use of the FDA 1572 form in Germany.
We would like to share some general information about this with you.
In Germany we have a federal structure of Regulatory Authorities. They are responsible for surveillance and inspection of investigators working under their responsibility. The ZLG is the coordinating body of the local authorities in Germany in the human and veterinary medicine area.
There were some inspection findings in relation to FDA 1572 forms signed by German investigators, like:
FDA Form 1572 was signed by the investigator. By signing, investigators commit to United States law. Studies in Germany are subject to the AMG [ German Drug Law ] and other European regulations, as applicable. It is a known fact that the FDA does not necessarily need Form 1572 from European investigators for IND studies.
An opinion of expert task force 05 – Clinical Trials – on this topic will be available here shortly: https://www.zlg.de/arzneimittel/deutschland/qualitaetssystem.html
The ZLG developed a position paper how to deal with the 1572 form and to avoid major inspection findings. This position paper is final and effective now.
Please note that this position is not a real new information. As per German Drug Law the investigators are obliged to comply to German legislation without exceptions.
In the past the signing of FDA1572 has always been an inspection finding, but now the German authorities have a common point of view how to deal with and now this issue constitutes a major finding.
See below translated from this paper
2. Question /Problem:
For inspections of multinational clinical trials by US sponsors or sponsors conducting a US regulatory trial (hereafter referred to as a «sponsor»), the FDA will often provide «FDA 1572» forms signed by the examiner. The form «FDA 1572» is enshrined in the Title 21 Code of Federal Regulations (CFR) 312.53 © «Responsibilities of Sponsors and Investigators: Selecting Investigators and Monitors» and is to be underwritten by the investigator if a clinical trial Examination as a so-called IND study (Investigational New Drug Study).
Under point 9 «Commitments» of the form, the examiner agrees with his signature u. a. to comply with the following requirements:
-Title 21 CFR Part 50 (getting informed consent)
-Title 21 CFR Part 56 (assuring that to IRB that complies with the requirements of 21 CFR Part 56 wants to be responsible for review and approval)
-Title 21 Part 312 (compliance with all other provisions concerning the obligations of clinical investigators and all other pertinent requirements)
-Title 21 CFR 312.62 (maintaining adequate and accurate records, making these re-cords available for inspections in accordance with 21 CFR 312.68)
-Title 21 CFR 312.64 (reporting of adverse experiences that occur in the course of the investigation)
These rules are US regulations that are not valid in the EU.
Title 21 CFR 312.120 also allows a sponsor to include sites outside the scope of the Investigational New Drug (IND) Regulations in the conduct of the clinical trial as so-called non-IND sites. The US requirements for conducting clinical trials are therefore also met if the clinical trial is conducted in accordance with international ethical and quality standards that are bindingly implemented in EU regulations. In this case, the signing of FDA Form 1572 is dispensable.
The question then arises as to how to proceed when finding a signed FDA Form 1572 or how it can be reacted to in the case of corresponding requests for admissibility.
The signing of the FDA 1572 Form by the investigator is inadmissible from the ZLG perspective, as the sponsor is provided with assurances regarding the conduct of the study in accordance with US law, which, in relation to various issues, do not comply with local or EU law.
For this reason, sponsors should preferably involve German test centers as non-IND sites in a clinical trial.
However, if the sponsor has decided to involve clinical trial sites in Germany as IND sites, it should be clearly stated in the investigator contracts that EU or national law generally takes precedence over US law.
In this case, the sponsor is expected to conduct a comparative analysis to identify discrepancies between the legal requirements in Germany / Europe and the US, and to demonstrate how to ensure compliance with EU or national primary legislation. If the FDA grants a waiver at the request of the sponsor, it must be checked whether this extends to all requirements of the CFR that do not comply with the German / European requirements, such as: Eg IRB requirements (Institutional Review Board), notification of security data, data protection requirements, archiving periods, etc.
The trial centers are to be informed by the sponsor about the requirements of the CFR, in particular those that oppose or supplement the German / European legal requirements.
The sponsor's comparative analysis and waiver (if applicable) granted by the FDA must be permanently linked to the FDA Form 1572 and, as well as the sponsor's documentation, placed in the trial master file and investigator folder. The documents must be submitted to inspectors upon request.
Finding a signed FDA Form 1572 without the documents described above constitutes a serious deficiency to be attributed to the sponsor. The classification of the deficiency attributable to the investigator should be based on the circumstances encountered during the inspection.