From The Editor | August 5, 2021

A Proactive Approach To Preparing For The Release Of ICH E6

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical


Approximately 25 years ago work began on a document intended to revolutionize and improve the efficiency of new drug development. The document, dubbed ICH E6, was intended to provide guidance for clinical trials conducted around the world. ICH E6 is quickly becoming a reality and will soon be updated for the second time in just five years.

For many in the industry, the updates could not come at a better time. Clinical trials are experiencing the emergence of new technologies, data is streaming from sources that did not exist just five or 10 years ago, and the industry continues to grapple with changes brought on (and necessitated) by the COVID-19 pandemic. With all that change occurring, how can you expect the new guidelines to impact you, your company, and your clinical trials?

A recent webinar hosted by Oracle Life Sciences addressed the issue with a team of experts including Crissy MacDonald, VP of client delivery for the Avoca Group; Andy Lawton, consultant for Risk Based Approach Ltd; Erika Stevens, principal consultant for Recherche Transformation Rapide; Marina Acosta Enslen, associate director of clinical management at Rho; and Elvin Thalund, director of industry strategy for Oracle Health Sciences.

When discussions around ICH E6 began in 1996, the conversations centered on the conduct of ethical and scientific clinical trials, the safety of patients, and having trust in the data being produced by them. With the release of (R2) in 2016, a couple of additional objectives entered the picture. Clinical trials have become more complex and along with that complexity has come cost increases and longer timelines. Fortunately, the industry has also seen the advent of new technologies that will help reduce the time and cost of trials, and efficiency became a point of focus for the ICH. For example, electronic reporting and oversight replaced paper-based methods. Risk assessment entered the picture.

Now that (R3) is taking center stage, what are the new developments? First, quality by design (QbD) will certainly play a role and will help define a company’s quality success factors. The concept of critical thinking will also come into play. After the guidance has been released, regulatory agencies will issue new regulations and drug developers will implement SOPs to ensure compliance. According to the panel, now is the time to start thinking about risk assessments and ways to make trials more efficient. There is no need to wait for the new regulations to emerge.

Get Everyone Involved

When making changes within an organization, properly training individuals is essential. It’s also important to ensure everyone is involved in the process. Proper training will help everyone be comfortable with the new SOPs and support should be gained at every level of the organization. The panel recommends starting with the CEO and gaining the support of senior management. Their thinking must be the first to change as that will empower change throughout the organization. A key point for them to keep in mind is that we are not attempting to add costs to the equation. The goal is to increase efficiency and focus on constant process improvement that is sustainable over time.

In terms of critical thinking, firms will require the ability to enable reflection and creativity. They will need foresight to think about what will be needed, the pitfalls that should be considered moving forward, and what has been learned that will enable sustainability for the organization and the ability to remain fluid. Improvements must be an evolving and evolutionary process.

According to the panel, drug developers must focus on being proactive rather than reactive. As an industry, companies tend to be reactive to new regulatory guidance. With ICH E6, there needs to be foresight and consideration of all stakeholders and how they may be impacted by the changes.

The transformation that takes place within a company must center on continuous improvement that is ongoing and enables management to be evolutionary and think about future transformation. “Don’t wait for ICH to provide you with guidance,” notes on panelist. “Take ownership and be prepared to implement new trial designs.”

Companies should also ensure their SOPs are not stagnant. Many companies have SOPs that have not been revised in a long time. Others are searching for a magic pill – an SOP template that tells them what they need to do. Neither scenario is very realistic. It is rare to find a standardized template that works for multiple organizations. SOPs allow for repeatability within an organization. Therefore, an SOP from a large organization simply would not work in a smaller biotech. Each SOP also has an output proving the process was completed. That output can also vary from one firm to the next.

Quality Concerns Remain

When it comes to quality, it seems the industry has not made much progress. Firms rely too much on auditing and retrospective document checking. Organizations remain siloed, meaning data and SOPs are not integrated. CTMS systems often do not talk to each other, and most companies have too many plans in place. At a senior management level, there is still a lot of dependence on budgets and timelines. For inspectors, that is a clear sign that the company does not have a great interest in quality.

What companies should be looking at is quality dependent on defined and measured quality. That is what will lead to continuous quality improvement. An integrated data system will avoid siloing and lead to integrated SOPs. At the board level individuals need to be looking at quality metrics, not just timelines. Timelines can be a useless measure especially if you know you’re not going to meet them only after they haven’t been met. Companies need quality by design. They need to specify quality tolerance limits, define what you expect, and measure whether you achieve it. These quality factors will continue to be a part of ICH E6.

Build Better Systems

Today companies perform study startup, study execution, and then close out the study. Different systems are used for the different phases. Oftentimes new systems are added without improving quality or efficiency. The panel recommends that the TMF be placed into the operational system. Investigators, sites, and auditors can all access the operational system in real-time and be involved with the quality process. Rather than purchasing additional systems, the focus will be on making operational adjustments.

Finally, don’t hold off on implementing a new plan until you know that it is perfect. It is easy to get paralyzed by not implementing a process that is still in draft mode. Companies will struggle with perfection and not implement something until it is perfect. Don’t hold off on putting a process in place because you’re not sure what the quality tolerance limits will look like. It’s better to think about the process you developed, document why you made the choices you did, move forward with it, and make adjustments as necessary. That approach will also show you are thinking about quality proactively.