Although my blog posts so far have been about the generalities of Standard Operating Procedures (SOPs), in future posts I’ll focus a bit more on their significance for GCP in clinical research. So, to begin, I thought I’d provide a bit of context. Besides, occasionally the question comes up about which GCP we should be following in Europe, implying that there’s another standard. So, is there a GCP standard other than ICH E6 GCP?
Yes, there is another GCP standard (aside from FDA GCP). Namely, the WHO’s Guidelines for GCP. And no, it’s not the pop group from the 1960s, but the World Health Organisation. The WHO started the process of developing guidelines in the late 1960’s. By the mid-1970s, one of their Scientific Groups formulated proposals and guidelines for research in the field of drug development, which eventually concluded with the WHO-GCP guidelines being published in 1995. These reports also provided the basis for the ICH-GCP, as an international guideline (published in 1996). So, the WHO-GCP guidelines and ICH-GCP were more or less written in parallel, by some of the same experts, and are basically similar. Differences in content and style reflect differences in their intended purpose.
On the one hand, ICH-GCP was intended as a harmonised guideline, in the three main ICH regions (the USA, Japan and Europe), to meet the “Technical Requirements for Registration of Pharmaceuticals for Human Use”. It was meant for adoption as a regulatory standard wherever trials were performed, irrespective of local regulatory requirements (unless these were more demanding than ICH-GCP). By contrast, WHO-GCP was intended as an informative tool for less experienced users, including regulatory agencies in countries where no other guidance existed.
The WHO also published a Handbook in 2002, which is a fairly comprehensive read. Wearing my hat as a trainer, I’d recommend it as a bit of “light” bedside reading for everyone involved in clinical research. It not only explains how to apply the principles of GCP, but provides Q&A, as well as references for ethics committees, investigators, sponsors and regulators. Covers all the bases, I’d say.
In the meantime, the principles of ICH-GCP were adopted into European legislation, in 2001, with the implementation of the Clinical Trials Directive (Directive 2001/20/EC). This Directive provided a common legal framework across Member States for monitoring and enforcing GCP standards applicable to clinical research. The GCP Directive (Directive 2005/28/EC) clarified the principles of GCP, with detailed guidelines setting out EU requirements for such aspects as: the manufacture or importation of investigational medicinal product (IMP); Trial Master File (TMF) and archiving; and inspectors and their inspection procedures – to name but a few. These guidelines are published in Eudralex Volume 10: Clinical Trial Guidelines.
So, to sum up, in case you don’t get round to that bedtime reading: the top-line difference between ICH-GCP and WHO-GCP is that ICH-GCP has 13 principles and WHO-GCP has 14.
But actually, it’s just that Principles 5 & 6 in WHO-GCP have been merged in ICH-GCP Principle 6. And, the order of some of the principles has been swapped around a bit. Apart from that, GCP is GCP regardless of whether it came from the International Conference on Harmonisation (ICH) or the WHO. But, let’s not forget, although one made it into the “Statute” books, the other serves to educate in those parts of the world that haven’t quite got their act together yet, in a legal sense.
There’s a big gold star waiting for the reader who can tell me where it says this in the 2002 WHO Handbook: “This handbook can be adopted or referenced by WHO Member States. Where national regulations or requirements do not exist or require supplementation, relevant regulatory authorities may designate or adopt these GCP principles and standards. Where national or adopted international standards are more demanding than WHO GCP, the former should take precedence.”