Navitas welcomes the opportunity to provide comments on this Reflection Paper...

Navitas welcomes the opportunity to provide comments on this Reflection Paper.

The current recommendations certainly take a significant step towards providing guidance on clinical trial management, with an emphasis on quality by design. This is particularly noticeable in the paper’s focused discussion on “Critical to Quality” factors. We believe that a revision to ICH E6 and E8 could go further, as proposed below.

Use of real world data

For the revised guidelines to stand the test of time, we should accept, and embrace, the fact that real world data sources such as electronic health records will become part of the standard data set for traditional trials of unapproved drugs. Therefore, we believe that to limit real world data to the annex on non-traditional trials is short-sighted. Instead, we would propose a reorganization of the annexes themselves; categorising them based on risk, rather than if they are traditional or not. This may mean that trials on unapproved drugs are still maintained, rightly, in a separate annex to those on approved drugs. However, it would remove the distinction primarily on data source. Software tools that can aggregate multiple sources of data for a variety of clinical studies that encompass very different risk levels already exist and are gaining prevalence in the industry. We should not limit our categorisation to the tools we have available today as they will no doubt continue to evolve rapidly.

E8 revision through working groups

In reviewing E8, working groups could also include members from outside the field of clinical trials. Quality by design has been an integral part of the manufacturing and automotive industry for decades and there may be opportunities for experts from these fields to help guide discussions. Pharma external SMEs would not only provide best practices and lessons learned but can offer a unique/outsider opinion on the current guidance.

Using a revised E8 as a platform to reference key documents is an essential step, and removes a significant pain point for users of this guidance.

Structure of ICH E6 revision and annexes

The revisions to ICH E6, and the associated annexes, focus on including and expanding “Critical to Quality” factors in the new guidelines. However, the CTTI list of Critical to Quality factors is extremely broad and there is a risk that ICH guidelines as a result, will simply duplicate considerable effort that has already been put into these and national clinical trial regulations. It may be more useful to provide context and metrics for these critical to quality factors. For example, it would be enormously valuable to provide insight into how risk based, or central monitoring can be effectively executed, globally. This can include circumstances where it is appropriate to use 100% central monitoring. Recall that the open letter explicitly details the absence of good information on central versus on site monitoring. Unfortunately this has received scant attention in this reflection paper.

Approach to revision

We are hopeful that the revisions to ICH E6 and E8 are not written in a similar style to this Reflection Paper as the readability of the reflection paper is extremely low. The Flesch Kincaid grade level score is 18 demonstrating that this document is “very difficult to read” and only understandable by postgraduate qualified readers. Although readers of ICH guidelines are likely to be highly qualified, this should not be a requirement to understanding the text. We sincerely hope that the final guidance is written in a more accessible fashion. Public consultation processes are an opportunity for all stakeholders to observe how ICH will conduct its own processes in the forthcoming revisions. If the internal processes result in unreadable documents, it does not provide stakeholders with confidence that the new guidelines will be different.

Communication with regulatory authorities

As outlined in the response letter to the EMA and ICH, communication and transparency are key issues with the current process. This results in groups feelings unheard, frustrated, and at odds with regulators. Furthermore, silence or lack of openness impacts execution of clinical trials and ultimately affects the development of new products and treatment of patients. The reflection paper does take steps to address this concern through stakeholder meetings and an open invitation for comments, however, it does not directly address how new guidance will allow for two way communication between regulators and companies. We recommend that a new approach is taken to encourage openness between both parties. An ideal solution would utilize current online resources to hold forum discussions, promote an open answering of questions, and allow the public to view responses/best practice guidance.

In summary, the reflection paper outlines several important areas for expansion and update however, we suggest that the revisions expand further. There should be more clarity around risk based monitoring and how critical to quality factors should be used. A different approach to the annexes should be employed, categorising trials by risk, rather than the extent to which they are traditional. New regulations should be clear and concise so that they are of practical use. Finally, ICH should strive to improve the level of two way communication to ensure understanding, promote ongoing guidance, and provide transparency.

Thank you once again for the opportunity to provide a response.

About Navitas:

Navitas integrates the proven Life Sciences capabilities of the legacy brands under its parent TAKE Solutions to offer end-to-end solutions to Biopharma companies. We have built the Navitas team specifically to deliver subject matter expertise and insights to our clients, to develop pragmatic solutions together, and to support their deployment and operation. We deliver advice, process and IP-driven solutions, and outsourcing services in Clinical, Regulatory and Safety. The team comprises of a range of experts from the worlds of Regulatory Affairs, Pharmacovigilance, Clinical Development, Life Sciences Big Data, Technology and Consulting.

We are proud that our legacy businesses have served the sector for over 20 years and have allowed us to work with 100 of the top Life Science companies. With a global footprint across the Americas, Europe and Asia Pacific, our team has now grown to over 1500 staff. For more information, visit


Latest News


ICH Reflection on “GCP Renovation”: Modernization of ICH E8 and...

Navitas welcomes the opportunity to provide comments on this Reflection Paper... Navitas welcomes the opportunity...


Navitas Life Sciences Augments Global Executive Management Team

Navitas Life Sciences announced the appointment of Dr. Krishnan Rajagopalan as Chief Growth Officer....


Navitas Networks announce Forum dates for Spring, 2017

The Navitas Networks are pleased to confirm the dates for our upcoming Spring forums... ...


Navitas Launches Labeling Assessment Express

Regulators are changing the way they look at labeling. The emphasis is on ensuring...


BioVectra chooses pharmaREADY for eCTD Solution

BioVectra has chosen pharmaREADY for its eCTD requirements. BioVectra, located in Canada, manufactures...


Navitas at DIA's 10th Annual Forum for Qualified Persons...

Navitas Principal Jeffrey Ho will present "Efficient content management for the compilation and...


News 2016

[row id="1" class="ROW_CLASS"] [col class="span12"] 02 Nov 2016 AbbVie and Navitas Present Case Study on the Evolution...


Navitas releases paper on CDISC, the standards and why the...

The FDA (and eventually, regulatory agencies from around the world) will require clinical data...


AbbVie and Navitas Present Case Study on the Evolution and...

At 10:30a.m. (East Coast Time) on September 22nd, Navitas and AbbVie will...


Navitas Networks announce Forum dates for Autumn, 2016

The Navitas Networks are pleased to confirm the dates for our upcoming Autumn forums....


Navitas Celebrates 100th pharmaREADY customer

pharmaREADY is Navitas’ intuitive and easy to use, fully integrated, regulatory compliant, web-based suite...


Navitas' PVTech Summit Defines Future Success

Navitas’ PVTech Summit was held on June 15th at the Hudson Hotel in New...


Navitas Welcomes Tara Baer to Navitas

Navitas is pleased to welcome Tara Baer, who joins Navitas' Regulatory Practice. With over...


Navitas Speaks at Sparta Connection in Orlando

David Gwyn, Navitas' Technology Practice lead, will unveil idmpREADY at the Sparta Connection conference...


Navitas Earns Speaking Sessions at DIA’s 52nd Annual Meeting

In two different sessions, Subject Matter Experts from Navitas will address new challenges facing...


Navitas is pleased to announce the introduction of our networks...

Navitas' inaugural pvindia meeting took place in Mumbai on Thursday 03 March, 2016. ...


Navitas Announces the Inaugural pvindia Forum

Navitas will soon be adding to our portfolio of industry leading networks with the...


Navitas Relaunches is Navitas' next generation website for its fully integrated, regulatory compliant document management,...


Steve Arlington, Navitas Advisor, Spoke on the Challenges, Opportunities and...

Steve Arlington, Navitas Advisor, Spoke on the Challenges, Opportunities and Future of the Pharmaceutical...


The changing trends in drivers of life sciences R D...

Outsourcing is not new in the life sciences sector. Clinical research outsourcing, contract sales...