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Edited by: Lesly Atlas and Pam Sobotka, Linking Leaders, LLC
Linking Leaders, host of invitation-only roundtable forums for clinical trial executives, has witnessed the rapid advancement of quality approaches supporting modern clinical trials. Quality professionals are in the process of transitioning to the role of quality leaders with specific capabilities to initiate and support Quality by Design (QbD) principles, as they currently have or will acquire skills and experience to bring added value to QbD and Quality Risk Management (QRM) approaches to clinical trials. Historically, the Quality Assurance (QA) organization has been viewed as a separate, independent auditing entity. Across the clinical development enterprise, the mindset is shifting from one of “quality as a rule” to one of “quality as a culture” where compliance is assured as part of the overall quality management and where quality and compliance is everyone’s responsibility. In addition, quality professionals, regardless of whether they have quality or compliance titles, should work together with Operations professionals to embed QbD in clinical development and clinical trials execution from study planning through completion. Rather than be an identifier of retrospective problems, QA must position itself as a bridge to solutions. Linking Leaders asked several key QA professionals for their perspective on how the role of the quality professional is being re-defined as a catalyst for the transformation of the design and execution of the modern clinical trial.
Linking Leaders: What do you feel are the fundamental skills of the quality professional in the current environment, and how must these evolve to support and ensure success in the future?
Fryrear: Since 2007, the expectations for quality in clinical trials have evolved rapidly. The concept that was emerging at that time, being advanced most strongly by FDA and EMA, was leveraging approaches to quality in clinical trials that were traditionally seen in manufacturing. These are the principles of a quality management system (QMS), such as those found in ICH Q10, and quality risk management. The clinical trial enterprise did not embrace these early on and, in many cases, it was a mix of befuddlement or dismissiveness that these truly only applied to manufacturing. After a few high profile regulatory agency enforcement actions and rejections of products due to quality questions, the industry started to take this seriously. The problem has been that you can’t just flip a switch and have QMS and QRM experts in clinical QA, nor is it a successful strategy to simply apply solutions developed for manufacturing. The new clinical quality professional needs to have developed those skills and be able to apply them in the context of clinical research across all contributing disciplines, e.g., stats, data management, laboratories, etc. The QMS elements—CAPA, change management, etc.—are essential.
Wilczek: In addition to the obvious high level of proficiency with current GxPs, the current regulatory environment requires a quality assurance auditor to possess fundamental interpersonal skills of diplomacy, persuasion, tactfulness, and influence. With the change of regulatory requirements around the world mandating QbD and a risk based approach, it is essential that the auditor’s role evolve to meet those demands. Additional needed skills include the ability to analyze data, understand RCA and CAPA processes and outcomes, and an ability to drive continuous process improvement. Auditors will need to be able to identify risk and failure points within a system and process, establish a solution, and the conduct of error analysis. They will need to see patterns and learn from trends and ensure proper escalations. Providing real time feedback to the stakeholders will be an important function of the evolving role of the auditor.
Driscoll: There are several technical and behavioral competencies we include for our quality professionals including, clinical expertise, attention to detail, teamwork, communication, influencing, time management, and cultural agility. There are also several areas that I consider fundamental and where we must evolve to ensure future success. Flexibility is critical because although there are processes overarching activities being performed, a quality professional has to be able to understand and help implement these in the context of the local environment. There may be multiple ways of achieving a given goal, while still remaining compliant with process requirements and regulations. In addition, one of the key aspects is the ability to identify potential issues upstream in the process and help teams and business process owners with risk assessment and mitigation strategies. Systemic evaluation and assessment are important because not only should a quality professional be able to identify an issue or gap with respect to a given process, but should also be able to understand how that fits in the larger context, the relevance of this issue with respect to the broader goal. This also helps from the perspective of evaluating the “severity” of the issue and identifying if additional activities would be impacted by this issue and help address this. Root cause analysis (RCA) and investigation skills are needed to be able to identify all possible issues and then subsequently be able to understand the overall impact (as described above). Good interpersonal and communication skills are required to be able to explain and convince auditees of the validity of the observations being raised. Negotiating skills are also an asset as in several instances, quality professionals are interacting with senior managers and need to get their point across while still being mindful of the context in which this audit is being performed. Finally, decisiveness is a needed skill, since quality professionals need to be able to make an assessment and help support the organization in the implementation of a prompt remediation.
Bajpai: The fundamental skills of today’s quality professional include conducting audits, gathering metrics, trending, and providing an overall pulse on the state of the QMS. The new quality professional is someone who can contribute to the various phases of the quality continuum. This entails combining cross-organizational experience with knowledge of regulations, providing compliance guidance, and utilizing trends from compliance reviews, audits and inspection outcomes for data-driven quality improvement. This new role may also serve to inform the organization with regard to the implementation of risk-based monitoring. The evolved quality professional should also have expertise in using methodologies for driving RCA for more comprehensive CAPA plans for significant issues and to guide the organization in effective quality improvement efforts.
Linking Leaders: What are your thoughts on where quality professionals reside in the organization? How might this evolve to better suit the emerging expectations and needs?
Driscoll: QA specifically must remain an independent function from clinical and development lines executing clinical trials to minimize bias and ensure impartiality in the assessments being performed. That being said, quality individuals or processes should be imbedded in all steps of a given process, and it is beneficial to the teams to have quality representatives providing support to some of these activities, as they are particularly knowledgeable about these processes and can provide advice. They can act as the “first line of contact” to teams while larger and more complex issues may be escalated to QA for support. I believe a model of first line quality and operational quality is paramount within a QMS.
Bajpai: We have to broaden the definition of a quality professional to include any group that might be involved in overseeing the quality of clinical trials and informing on the state of the QMS within an organization. This should include both the operationally aligned compliance and traditionally defined QA auditing groups. QA groups are typically set up as separate, independent auditing entities, conducting site, process, and document audits while compliance groups are aligned with the business or operations groups.
Where I think the existing models can further evolve and become part of the full quality continuum is for quality professionals (compliance and QA as currently defined) to work more closely and in congruence with each other. Sometimes, these groups are involved in separate activities aimed at the common goal of ensuring quality and compliance in clinical trials. When these groups are closely aligned and have an understanding of each other’s information and perspectives, they are more successful in driving a streamlined quality continuum and improving the state of the QMS collectively.
Fryrear: Right now, I would say that the quality professionals in the QA organization are best positioned to champion these concepts and play an educator, advocate role across areas, and be the catalyst for quality transformation. However, for the concepts to get traction, everyone working in clinical research will have to have a certain level of understanding. Again, I would look to QA to do this education. Ideally, as we move to a culture of quality in the industry, everyone would understand these modern quality approaches and how to apply them.
Linking Leaders: In what ways are companies beginning to define specific quality system roles beyond “Auditor” or enhancing the skills of existing auditors?
Fryrear: First, let me say auditing is important and always will have a place. How we approach auditing will certainly have to evolve, perhaps leveraging much of what we are learning about monitoring. That said, most auditors I know have always been leveraged as consultants. Much of that traditionally has been focused specifically on GCP compliance – does a situation comply or not. That’s certainly important, but in the current environment, being able to guide on an approach to a matter – a quality Sherpa, if you will – would be very powerful.
Driscoll: Auditing is just one component, usually an assessment performed post completion of an activity. QA colleagues can provide support in a multitude of ways upstream in the process, ranging from providing guidance on requirements for the development of study related documents, support in risk mitigation strategies, and development of processes. Skills of existing auditors can be developed by exposure to other aspects of the business, such as involvement in process development initiatives, rotational assignments in other functional areas to gain exposure and more in depth understanding of the processes, mentoring colleagues with other skill sets, shadowing or on the job training with more experienced and senior colleagues, and webinars and other industry sharing of information.
Linking Leaders: What types of roles do you feel will be necessary in the modern quality organization?
Bajpai: The quality continuum and the role of the quality professional within it will become more relevant as the biopharmaceutical industry begins to shift from reactive error detection to adopting the principles of QbD and QRM, which in my opinion, requires building, managing, and improving quality in a proactive, systematic, data-driven approach. In addition to error detection and quality checks, quality professionals will offer collective analysis and signals from data trends emerging from quality and compliance activities. This will inform the organization towards prioritizing and driving quality improvement in the current processes. The quality professional has a key role in applying the risk-based quality framework to clinical trials and play a pivotal role in educating on the quality continuum and being an advisor of GCP incidences which might occur during the course of a study or program.
Fryrear: I’ve touched on many of these already – champion, educator, quality guide. These certainly aren’t traditional titles and aren’t meant to have job descriptions written for them – although it certainly would be exciting to have a job title of “Quality Champion,” but I do think these describe roles that are needed. Thinking ahead, it certainly would be useful to have roles that can lead in QbD.
Driscoll: I think that there may be a potential gap from the perspective of individual colleagues “owning” quality. In reality, if all colleagues implemented and embedded quality processes within their daily activities, then QA could evolve to more of a “consultant” role and could strategize oversight activities differently. That being said, currently, I think that there is a need for QC activities and quality support and oversight in the various functions as “go to” colleagues, inclusive of QA oversight. For example, in the data mining and analysis area, we need metrics managers’ help to gauge previous outcomes to support future performance. Likewise, we need QRM experts to drive oversight strategies through integrated risk identification and assessment.
Wilczek: The ability of a QA organization to understand emerging technology is an increasing necessity for an auditor to improve their productivity and data analysis, definition of risks and trend analysis, and activity dependencies. Quality specialists who have backgrounds in forecasting or data analysis will be crucial to help define and develop metrics to track trends in quality operations and to provide service to other departments within an organization.
Linking Leaders: What do you feel is a viable approach to transforming the role of the quality professional as one that enables the QbD and QRM approaches to clinical development?
Bajpai: There are many approaches for implementing QbD and QRM concepts within an organization. I have tried to simplify the way I think of defining, building, and implementing quality proactively. In the GCP environment, I think QRM starts with proactive risk assessment and mitigation planning. In practical terms, the approach for building a quality continuum involves three distinct phases or building blocks aligned with specific phases of a clinical trial. These include quality planning, quality improvement, and quality management aligned with three broad phases of a clinical trial: study startup, study duration, and study closeout. The activities and output of each phase continues to the next phase and is thereby cyclical in nature. I have utilized this approach throughout my career, refining it as I went along. There is much more granularity in this three-phase process which can help an organization adjust their existing process to build in these quality enabling steps. In my experience, this model can be applied in centralized or decentralized, large or small quality and clinical operations groups. The key to successful implementation is strong collaboration, trust, and minimized silos between the quality and operations groups.
Fryrear: First you have to have the deep education and understanding of these topics. This doesn’t really happen in on-the-job-training. It is a significant challenge because we are talking about people who are already busy and carving out time for this education. However, professional development of our employees is an expectation of any leader. It can and should be incorporated into that. We also need some opportunity to experiment here. Again, an open minded manufacturing quality professional doing a tour of duty in clinical, partnering with clinical QA colleagues can be very valuable if managed well. The key here is that we are not talking about GMP coming in and steam rolling solutions onto clinical. It’s a far more sophisticated approach of looking at what is needed and being pragmatic about what works. I know that this idea makes many of my clinical colleagues shudder, but it’s an approach.
Wilczek: It’s necessary to ensure that audit requests, planning, preparation, audit findings, and sharing of data and applicable information are easily accessible for necessary stakeholders. The quality professional should interact very closely with clinical development at the earliest stages of program development. Only in this way can quality features be included as an integral component of the team.
Linking Leaders: How can quality professionals enhance influence across the organization?
Driscoll: I believe that we can enhance influence first by education and generating analytics, performing trending of audit and inspection metrics, and sharing this information with study teams and business process owners for awareness and to influence process enhancements and quality thresholds. This influence can be furthered by involvement in risk assessments being performed, and with support to develop risk mitigation strategies. Finally, quality professionals can drive forums to cascade quality culture and guide teams to adhere to quality policy and goals across the organization.
Wilczek: I think quality professionals can exert influence by ensuring that data exchange is part of the process of workflow within an organization and not a separate process. The quality professional must strive continually to represent themselves as concerned allies, not as adversaries.
Fryrear: Interesting question as it’s one thing to be present and an entirely different thing to influence. The key to being able to influence is to establish credibility and provide meaningful solutions that work on actual problems. Alternately, saving the day in a tough inspection also works.
Bajpai: Quality professionals should be key partners with operation teams to guide quality planning, quality management, and quality improvement activities as described for implementing a “quality continuum.” It is critical for an organization to have visibility into the state of their QMS at all management levels. This can be achieved by systematically collecting and analyzing quality and compliance data and connecting the dots for the organization. Quality professionals can play a direct role in simplifying the message to illustrate impact of noted trends and empowering the organization to make improvements at all levels. This approach can allow organizations to build quality into their clinical trial process and establish a structure in which to plan, measure, and improve quality in a continuous, systematic, and data driven manner.
Collectively, quality professionals are powerful catalysts for driving and establishing quality and compliance as a “culture” rather than just a “rule” within an organization where compliance is everyone’s priority. The key to success is establishing a common language, partnership, and evolved leadership between operational and quality organizations for information sharing, minimization of silos, collaboration, transparency, and communication.