What are the differences in SOPs for clinical trials in Europe and the United States? Despite the fact that FDA and the European Medicines Agency are increasing their cooperation and collaboration there are still some formidable obstacles. One is the difference in regulations. The other is how much influence ICH E6: Good Clinical Practice: Consolidated Guidance has in different parts of the world. Today we have a Guest Commentary from The SOP Doctor, Dr Marie McKenzie Mills MICR, CSci, CBiol, MSB, a clinical scientist and trainer from the United Kingdom. She is here to give us a European perspective on SOPs. In 1996, Marie established McKenzie Mills Partnership (MMP), providing consultancy services including training, medical information, medical writing, and clinical research.
I will be publishing a post in Marie’s blog this weekend. Trans-Atlantic Cooperation!
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Is there a legal requirement to have SOPs for GCP in Europe?
by Dr Marie McKenzie Mills MICR, CSci, CBiol, MSB
Back in January, in his post “reflecting on the TMF”, Carl mentioned that the ICH Topic E6 Guideline for GCP may not appear to receive the same emphasis from some regulatory authorities as in the past. His post raised a flag about whether there’s a GCP standard other than ICH E6 GCP, which got me thinking. In Europe, a similar concern often pops up along the lines of: which GCP should we be following? So here goes with my answer, particularly for those of us affected by European legislation, with a wee bit of context to explain it.
In Europe, ICH GCP was adopted in July 1996, and became operational in January 1997. Despite having no uniform legal framework for implementation, it was largely adhered to within the European Community (EC) as a set of 13 internationally recognised principles for conducting clinical trials, founded in the bioethical principles that were established in the Declaration of Helsinki. But, its adoption as a regulatory standard was neither complete nor uniform.In 2001, Directive 2001/20/EC – legislation known as the Clinical Trials Directive – eventually provided a common legal framework across Member States for monitoring and enforcing GCP standards applicable to clinical research implementation. However, Directives have to be transposed into national law, in each Member State (within three years of their publication). This created scope for differing interpretations of the intended regulatory requirements, somewhat at odds with the goal of harmonisation. Even so, ICH GCP is the cornerstone standard within both the Clinical Trial Directive (Article 1 (3)), and the GCP Directive (Directive 2005/28/EC: Introduction, points 1 and 8; Chapter 1, Article 1 (1a)). So, far from receiving less emphasis, its principles have been adopted in both Directives, where it provides a basic standard for the conduct of clinical trials in a “set of internationally recognised ethical and scientific quality requirements, which must be observed for designing, recording and reporting trials that involve the participation of human subjects”.
This then brings me to the question about requirements for SOPs. Even if this requirement isn’t explicitly stated in European legislation, the burden to satisfy it exists nonetheless, particularly for sponsors because, according to ICH GCP 5.1.1, they’re responsible for “QA and QC systems with written SOPs to ensure that trials are conducted in compliance with the protocol, GCP, and the applicable regulatory requirement(s)”. Likewise, IRBs or IECs – as they’re better known across Europe – also need to have SOPs for their functions (ICH GCP 3.2.2).As it turns out, in the GCP Directive, the requirement for SOPs is emphasised less for sponsors, and more for Member States, since their inspectors need appropriate tools for verifying GCP compliance (Chapter 6, Inspection Procedures, Article 26: “Member States shall establish the relevant procedures for verification of good clinical practice compliance. The procedures shall include the modalities for examining both the study management procedures and the conditions under which clinical trials are planned, performed, monitored and recorded, as well as follow-up measures”.
So there you have it: SOPs are required tools for sponsors to ensure GCP compliance; and, for inspectors they’re required tools for verifying compliance. As an all-encompassing requirement in the GCP Directive it often seems to escape everyone’s notice, perhaps because it appears understated. But, it’s there in Chapter 2, entitled Good Clinical Practice for the design, conduct, recording and reporting of clinical trials in Section 1, Article 2 (4): “The necessary procedures to secure the quality of every aspect of the trials shall be complied with.” I don’t know about you, but I think that’s all about SOPs. What do you think?
Links to the Clinical Trials Directive, GCP Directive and the ICH GCP guideline can all be found on the European Medicines Agency website on the link below.
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For more information about Europe you can read:
Applied Clinical Trials, View From Brussels by Peter O’Donnell
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