Top 5 Challenges to ICH E6 Rev 2 Compliance


Let’s look at the intent and purpose of the revision … The revised Addendum is proposed to modernize ICH E6 and enable implementation of innovative approaches to clinical trial design, conduct and management that will better ensure subject protection and data quality.

This is a significant and positive step, but we will only realize the benefits if we embrace the intent behind the revision and our processes allow us the latitude to be innovative and focus on what is critical to success.

The top 5 challenges to implementing compliant processes:

1   Assessing scope and impact

Determining how far reaching the revision is across the Quality Management System (QMS). The revision is not just about monitoring practices, the principles of quality management will have cross functional impact.


2  Creating a culture that focuses on ‘what matters’

For many years our functional practices have regurgitated what has been done in the past.  The intent of the revision is to make us think about the specifics of a trial and how best to implement and manage what is important for the trial.


3  Over complicating the process

Coming from the position of ‘one size fits all’ approach, we are so used to providing or being provisioned with very specific and clear processes that apply to all trials, indiscriminately. There is a temptation to take a similar approach when implementing revision 2.  However, because the very basis of the guideline is to determine an appropriate approach to conducting and managing the specifics of each trial, trying to set out a process for every possible permutation will create a very complicated approach that will be difficult to implement and to demonstrate compliance with.  Or, conversely, trying to fit all trials into pre-defined ‘boxes’ in an attempt to set out detailed processes for fewer permutations runs the risk of missing the important nuances of the trial.  Instead, set the quality expectations for the organization, document the standard practices, and allow the study teams assess, define and document the specifics for their trials.


4  Over documenting the process

Following on from item 3, standard processes are often documented in SOPs and repeated in study plans resulting in the study plans being difficult to read, and the important study points are often overshadowed by the copious amount of standard practice.  Set the standard practices with the QMS, the quality expectations should be such that standard practice is followed unless specified otherwise in the study documentation.  Allow the study documents to focus on what is important and different for that study. This has the added benefit of supporting challenge 2, if we can clearly identify what matters in our study documents, without the foliage of standard practice, we can focus on what matters.


5  Temptation to make E6 R2 a bigger change than it needs to be

Keep it simple, it doesn’t need to be a big bang approach, with new roles, functions, processes and technology.  The intent behind the revision can be better achieved by some simple process changes, clear expectations on standard practices, some simple tools to facilitate process change, and education on why we are changing how we do things.  We don’t need to do it all at once.  Organizational roles, functions, processes and technology can and will evolve as we gain in experience.



Keep it simple, pragmatic and effective to avoid inertia.




TRI are specialists in helping companies understand and implement ICH E6 Rev 2. Whatever your time frame, current capabilities and needs, we are able to help. For more information please click on the link below to contact us directly:

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