Merck’s Deborah Driscoll on TransCelerate’s QMS Initiative

Recently, TransCelerate's Quality Management System (QMS) Initiative published an article that delineates specific mechanics that will be used to build a QMS Conceptual Framework to facilitate and encourage proactive approaches towards executing Good Clinical Practices, and proper change management expected to support a culture of quality.  This interview with Deborah Driscoll, VP of Quality Assurance at Merck Research Laboratories and Lead of the TransCelerate Initiative will elaborate on this framework.

Moe Alsumidaie: Can you outline the QMS initiative? How did it come about and what is it going to achieve?

Deborah Driscoll: In February of 2014, heads of quality from large and small biopharmaceutical companies were asked to gather and discuss challenges facing the industry when it came to quality. It was noted that many companies were struggling with issues related to managing quality in their clinical trials and this was, likely impacting regulatory agencies’ time and resources; was delaying submission reviews around the world; and importantly slowing the delivery of innovative medicines to patients. 

We spent time identifying the root cause and found that many of us were trying to implement ICH Q10 in clinical trials, which is a pharmaceutical quality system developed for Good Manufacturing Practices (GMP). We were also looking to follow other international standards, such as ISO methodology. It became evident that nothing quite fit the clinical space because, unlike manufacturing, you don’t get to stop the line; you don’t get to discard a batch. You have to go forward with the data you collect because it's from patients. There is no opportunity for a complete do-over for clinical work. 

We developed the following the problem statements: How do we improve quality in clinical trials in a quality system framework that would improve efficiency for sponsors? How do we do that in an effective way that is voluntarily applicable to any company size, large or small? Those questions spearheaded exploratory work through funding, guidance and oversight from TransCelerate.

MA: Can you describe the work this initiative has done, and your findings?

DD: As part of the TransCelerate Clinical Quality Management System Initiative, we also reached out to biopharmaceutical industry initiatives, regulatory bodies and companies, as well as the research and contract research organization community, and reviewed individual organizations’ philosophy, guidance and other content regarding their overall perception on quality.

We also recognized that many industries outside pharma are quite good at quality systems and thought about how we can integrate those systems and practices into our industry. Equipped with this information, we developed the Clinical QMS Framework, and published it in a concept paper titled, "Enhancing Quality and Efficiency in Clinical Development through a Clinical QMS Conceptual Framework: Concept Paper Vision and Outline." 

We’re also focusing on two directives: issue and knowledge management. In issue management, issues aren’t handled consistently within organizations and we want to be sure that we are handling them well. We believe that an industry based on collected data can be better at issues management and developing better corrective and preventative actions (CAPAs). The area of knowledge management involves understanding how companies make use of information that they’ve learned from good quality programs, and leverage that information for protocols and therapeutic programs across the portfolio.  In the future, we hope to include other elements into the conceptual framework, including quality measurement.

MA: In your published QMS framework, you introduce two core concepts: Organizational Flexibility and Risk-Based Thinking.  Please elaborate on each of those core concepts.

DD: Organizational Flexibility. It’s important that we are flexible in how we develop and provide substrate on the framework because companies vary in size ranging from approximately 50 people to 80,000+ people, and organizations of quality range in size from one person to hundreds of people. How do we deploy a quality system that fits the needs of both? We know that some companies are process driven; they may have a business process or a network that drives CAPAs and deviations, whereas others have one person responsible for quality. The important thing is that the elements work in any way, and we expect companies will execute the QMS framework in new and different ways. An important consideration is that all of the elements have to work synergistically.

Risk-based approaches. When one considers risk in clinical trial conduct, it is critical to think about what’s important and what matters. We want to think about patient safety and appropriateness of the data, so that our actions have an actual impact on the patient. We want to be sure that it has a low-risk threshold: meaning that we are going to focus on that particular effect.

Data quality and integrity are very important for the accuracy of regulatory submissions and assuring that any claims that are made are well-supported by data. It also has a tremendous impact on the first issue that I mentioned, which is the study patient. Using the patient (primary) and data quality/integrity (secondary) as risk drivers allows us to decide how to best allocate resources when auditing and monitoring clinical trials.

MA: Can you describe your work with global regulatory bodies to align the QMS framework?  What are the outcomes of these discussions?

DD: Early in the initiative, we planned on engaging regulatory authorities when developing the QMS framework, and we believe that evolving towards an ICH guidance that focuses on a clinical quality management system framework would best benefit biopharmaceutical companies across the industry. We felt it was absolutely key to engage regulators as stakeholders in efforts to improve clinical quality systems when we developed our hypotheses and plans.  

We spent time talking with the FDA, EMA and PMDA to understand their thoughts on our hypotheses and to obtain feedback in terms of where they thought we should evolve. These agencies have requested an additional round of discussions, so they can be a part of and learn about the evolution of the framework. Their feedback has been helpful and has shaped the progress of our framework. Starting in 2016, we have plans to visit and obtain feedback from the Medicines and Healthcare Products Regulatory Agency (MHRA), Swissmedic, BPharm, Health Canada, and Anvisa, to name a few.

MA: What challenges do you expect to see when the biopharmaceutical industry adopts the QMS framework? Do you expect to see cultural challenges in order to implement this framework? 

DD:  It is really important that we focus on culture because things are different for organizations working within a clinical quality system. In many ways it is virtual, but it also requires a leadership commitment from the top, depending on the makeup of the company.

A key objective of quality requires leadership to be vocal and demanding, and an advocate in ensuring that quality expectations are clear. They need to make sure that staff are trained and available for all the functions necessary to execute a good quality system; there’s some change in thinking that needs to evolve based on any given company’s culture.

There needs to be organizational commitment to quality in an environment where quality has a voice, especially in clinical quality. Companies, in my opinion, tend to comingle good clinical practice and assume it’s the same as manufacturing practice. While the principles of good quality are likely the same, the way that you approach quality management may be very different than how it’s done in manufacturing.

Going forward, it will be a challenge, but, it’s a challenge we are willing to face and our objective is to get people in our industry to think about quality as it’s approached by a clinical quality system. Part of the QMS Initiative program is building a set of tools with change management and culture experts that can help companies ensure the sustainability, efficiency and effectiveness of a clinical quality management system. We want to avoid inefficiencies such as rework or redoing trials and that's why learning about quality and its importance as an investment is needed.