ICH GCP E6 (R2) Addendum

[Shahnaz]

I had read that Revision 2 to ICH GCP would be signed off in Nov 2016 a while back. Does anyone know if this has happened and if so when we can expect implementation? This is what I came accross when searching for more info:
http://rephine.com/need-know-ich-gcp-e6-r2-addendum/

[a123456]

The ICH press release of 17 Nov 2016 stated that :- "Global good clinical practice (GCP) guideline amendment adopted. The 1996 ICH guideline on GCP is one of the most significant achievements of the ICH process, establishing harmonised standards for clinical trials. The ICH Assembly adopted an important amendment (ICH E6(R2)) that aims to encourage sponsors to implement improved oversight and management of clinical trials, while continuing to ensure protection of human subjects participating in trials and clinical trial data integrity. This amendment will now be implemented by ICH members through national and regional guidance".

However the ICH website for E6 still (as of 29 Nov 2016) have only the draft Step 2b available and not yet the final step 4 version.

[a123456]

At last ICH GCP E6 R2 (version adopted date 09Nov2016) is published on ICH website
Despite the fact that ICH adopted GCP E6 R2 on 9th Nov 2016 and published a Press Release saying this on 17 Nov 2016, it was not until 30 Nov 2016 that they new draft appeared on the ICH website.
http://www.ich.org/fileadmin/Public_...R2__Step_4.pdf

[Shahnaz]

Many thanks for this

[ClinicalQuality]

I have a follow up question on this topic. ICH website indicates that each region is to determine the timeline for implementation of ICH GCP E6(R2).
Does anyone know how it will be implemented in the EU? For example, will Directive 2005/28EC be updated or will implementation coincide with implementation of the new CTR 536/2014 (which is not before 2018)? Does the EMA plan to publish further guidance before implementation?

[a123456]

ICH GCP E6 is guidance and not EU legislation. Although no one knows when this guidance will be implemented in the different regions, there was a suggestion at the Osaka meeting:- "Europe:- the Step 4 document to be adopted December 2016 by CHMP and as Step 5 will be published on the website, with most likely 6 months to come into effect. FDA:- publish it as a final guidance in the Federal Register and then post the guidance on FDA website. ----- does not expect that FDA will assign an implementation period.” No one knows for sure if this timetable will be implemented.
As I said, ICH GCP E6 is guidance and not EU legislation and hence there will be no need to update any legislation.

Of interest is the fact that the new CTR 536/2014 does reference ICH GCP:-
Whereas 43 "the ICH guidelines on good clinical practice should be taken appropriately into account for the application of the rules set out in this Regulation, provided that there is no other specific guidance issued by the Commission and that those guidelines are compatible with this Regulation".
Also Article 47 "Without prejudice to any other provision of Union law or Commission guidelines, the sponsor and the investigator, when drawing up the protocol and when applying this Regulation and the protocol, shall also take appropriate account of the quality standards and the ICH guidelines on good clinical practice. The Commission shall make publicly available the detailed ICH guidelines on good clinical practice referred to in the second paragraph".

[a123456]

ICH E6 (R2) Good Clinical Practice adopted by CPMP (Europe) Dec2016, effective 14June2017
Several of the links on the EMA website do not work correctly and some of the revision numbers may be muddled. . However it is clear that the EMA has adopted ICH GCP E6 (R2) and that it comes into "operation from 14 June 2017.
http://www.ema.europa.eu/ema/index.j...01ac0580032ec4

[a123456]

EU has adopted R2 (Step 5) on 15 Dec2016 with a "Date for coming into effect" of 14 June 2017"

[WillC]

Another item from the Addendum worth noting (under 8.1):
"The sponsor should ensure that the investigator has control of and continuous access to the CRF data reported to the sponsor. The sponsor should not have exclusive control of those data."

One interpretation of this is that a typical arrangement where a CTU hosts their own EDC system would be non-compliant (there is no local investigator copy of the data). It would be possible to modify an EDC tool to - say - save CRF PDFs on the investigator's local network but there are obvious complications of this approach.

It would be useful to get clarity from MHRA on this, ideally before they pay CTUs a visit with a particular expectation.

[Dorothea Regina Waser]

Could somebody tell me if there is any further change in regard ICH-GCP E6 (R2) step 4 versus step 5, beside the fact that it became effective? I am really puzzled. Many thanks!