Are you also trying to correctly interpret the wording of the new ICH GCP E6(R3) guideline? – Picture by FGK generated with AI
Come with us on a journey through the depths of the GCP jungle in search of truths ... and puns
We start with an overview of the changes which will be followed by various topics that our FGK regulatory expert (100% human, not AI!) will take apart and bring back together for you.
Here we go:
The 30 year old ICH E6 guideline, issued by the “International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use” with the title “Guideline for Good Clinical Practice” that is often referred to as “Good Clinical Practice”, “ICH GCP”, “ICH/GCP”, “GCP” is completely revamped, resulting in the 2025 version called ICH E6 (R3), which will probably be completed until 2026 with Annex 2.
- ICH E6(R3) has a new structure starting with an introduction and the principles of ICH GCP as in previous versions, but the glossary is stapled carelessly at the end of the booklet, it has even lost section numbers.
- The section with ICH GCP principles is followed by Annex 1, containing the familiar chapters about the ethics committees, sponsor, investigator, investigator’s brochure, clinical trial protocol, essential records and a new chapter on data governance, which accounts for most of the text expansion from 68 to 71 pages.
- Annex 1 describes principles for “traditional” interventional clinical trials. ICH GCP will be supplemented with Annex 2, which describes principles for clinical trials that incorporate decentralised and pragmatic elements and/or real-world data.
Apart from changes in the overall structure, the familiar topics of the larger chapters are still there. However, with only few sentences left unmodified, content and wording was revised and updated in a comprehensive way. For example:
- The previous "subjects" are now called “participants”, adverse events are now “unfavourable” instead of “untoward”.
- Unlike the versions of ICH GCP until ICH E6 (R2), ICH E6 (R3) no longer assumes that the interaction with the ethics committee may be made by the investigator alone, but acknowledges that this might be the task of the sponsor.
- The provision to retain essential documents “until at least 2-years after the last approval of a marketing application […] or at least 2-years have elapsed since the formal discontinuation of clinical development” is replaced by a reference to “applicable regulatory requirement(s)”.
- This type of reference is a general feature: ICH E6 (R3) refers to “applicable regulatory requirement[s]” 108 times, but ICH E6 (R2) only 52 times.
- In addition, in ICH E6 (R3) you find “remote” or “remotely” 10 times, in ICH E6 (R2) only 2 times. This is associated with new options to obtain consent outside of the trial centers, ship medication directly to patients, conduct remote monitoring.
- Finally, while ICH E6 (R2) has 127 hits for “data”, ICH E6 (R3) has 306. In a series of short articles we shed some light on new aspects of ICH E6 or on recently emerged points of friction with the EU Clinical Trials Regulation.
In the EU, ICH E6 (R3) with Annex 1 will become effective from 23 July 2025. Annex 2 might become effective in late 2025 or in 2026.
It is not clear what sponsors have to do for transition from ICH E6 (R2) to ICH E6 (R3). In the EU, authorised protocols, investigator brochures, consent forms and SOPs about authorisation processes do not need to be updated to add new items and update definitions (since this is governed by the EU Clinical Trials Regulation and national rules). However, sponsors might revise their processes for data and document handling, for oversight, monitoring, risk management, etc.
Does this have to be done even for a clinical trial that will end in two months? Traditionally, unlike legal acts, ICH guidelines have no provisions for transitions that allow the conduct of ongoing clinical trials according to the recently superseded guidelines. However, since ICH guidelines are only guidelines, sponsors could probably prepare justifications for not transition clinical trials that, e.g., have already entered their second half.
Read the guideline for yourself: ICH E6(R3)