By Ed Miseta, Chief Editor, Clinical Leader
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TransCelerate Biopharma is all about collaboration. The group’s goal is to identify, prioritize, design, and facilitate the implementation of solutions to help sponsors efficiently and effectively produce needed medicines for patients. Its initiatives certainly bear that out. The non-profit organization currently has 18 member companies engaged in developing 16 initiatives to forward its collaboration mission. Those initiatives include risk-based monitoring, shared investigator platforms, site qualification and training, and a common protocol template.
I recently had the opportunity to speak with Deb Driscoll, VP of quality assurance at Merck and lead of the TransCelerate QMS (quality management system). Driscoll was able to discuss how the initiative aims to bring together industry stakeholders to explore ways to improve quality, and the progress it is making.
Ed Miseta: Tell us about the TransCelerate QMS initiative.
Driscoll: The goal of this initiative is to promote quality across the industry. As part of this initiative, we developed an initial vision and outline for a conceptual framework for a clinical QMS, which includes 9 elements supported by 4 foundational aspects. As we established this concept, we kept in mind several principles: the framework needed to be proactive – to focus attention on preventing risks from materializing – and it needed to be flexible and adaptable to account for the diversity of organizations that may have interest in voluntarily implementing it.
Foundational aspects are key to establishing and sustaining a clinical QMS – for example, understanding the context helps organizations fully appreciate the internal and external environment relevant to the company and its objectives, and permits tailoring of a clinical QMS.
There are seven horizontal elements of a clinical QMS that are intended to integrate quality and risk-based thinking across clinical development activities (similar to new ISO 9001 focus on risk-based thinking). One example is partnering, which includes collaborations in which organizations jointly develop a product as well as outsourced activities. Partnering focuses on prospectively understanding the needs and challenges of all involved parties, and on proactively and collaboratively identifying and addressing risks inherent to the activities that are the basis of the partnership.
The other elements are:
- Resources, roles, and responsibilities
- Risk management
- Issue management
- Knowledge management
- Documentation supporting achievement of quality
This conceptual framework provides professionals working on clinical trials with the foundational principles needed to develop and progress towards systems for managing quality in a clinical environment. The framework therefore represents a significant step forward on the industry’s path towards a workable and more efficient clinical QMS. To take the clinical QMS form concept to practice, clinical trial professionals need more detailed guidance than what we have covered in the Conceptual Framework. TransCelerate’s QMS initiative has therefore been working with ICH and health authorities around the world to encourage ICH to issue guidance on what an effective clinical QMS might look like.
In addition, TransCelerate’s QMS team will develop tools and perhaps also more detailed guidance, which would be developed in conjunction with other stakeholder groups, on how to implement and operationalize a clinical QMS effectively and efficiently.
Miseta: Why did TransCelerate feel this initiative was necessary?
Driscoll: Various health authorities have been advocating for clinical QMS publicly; further, quality requirements are fragmented across guidance documents. In the absence of guidance, companies may use ICH Q10, but it’s not fit-for-purpose. It is critical therefore that ICH or other regulatory authorities provide harmonized guidance to the industry. In the interim, we have published in our Conceptual Framework the building blocks that we feel would be essential to any efforts by ICH or by any clinical organization to develop a workable clinical QMS. And, if necessary, we would consider joining with other stakeholder groups to develop more detailed and practical guidance in this area.
Miseta: For sponsors, how will the initiative improve the quality of clinical trials?
High quality built into clinical research through Quality by Design principles, which fit under the umbrella of a clinical QMS, can expedite trial completion by reducing and/or eliminating errors that result in rework. Therefore, it can deliver high quality data supporting important health authority submissions. Further, high quality submissions can also lead to faster review cycles.
The initiative can also help to get new medicines to market faster. Following the elements of the clinical quality management system can support the embedding of quality throughout the conduct of studies, which will in turn contribute to high quality data and improved submissions. This can lead to expedited review cycles and approvals, therefore accelerating the timeline of bringing medicines to market. I would add that high quality data and the resulting submissions can potentially lead to expedited review cycles and approvals, therefore leading to the faster delivery of important medicines to the patient community.
Miseta: Why is this framework more flexible and proactive than other approaches?
Focusing on clinical quality rather than trying to utilize ICH Q10, which focuses on manufacturing quality, allows for the flexibility necessary for clinical trial conduct. Additionally, the conceptual elements of the clinical quality management system described in our work are flexible and scalable in ways that a large, medium and small companies can implement.
Miseta: Can we expect this initiative to improve clinical trials at every phase?
Driscoll: That is certainly our goal. A well-functioning QMS should improve clinical trial conduct from the drafting of the protocol all the way through to the preparation of the submission to a regulatory agency. Additionally, the Quality by Design principles embedded throughout study conduct should provide a quality experience for the sites and patients as well. It is truly an all-encompassing approach.
Miseta: One element of QMS is issue management. How does that work and how will it impact companies conducting trials?
Driscoll: Issue management provides a proactive approach for end-to-end management of issues with escalation (triage based on the impact), and uses existing methodologies for the full benefit (root cause investigation, impact analysis and Corrective and Preventive Actions (CAPAs)).
It can also validate the effectiveness and sustainability of the corrective and preventive actions from the CAPA process.
Further, it can introduce a methodology for trending and analytics that will signal potential risks, enhance risk management strategies and drive continuous improvement through predictive analytics.
Miseta: What feedback have you received from regulators thus far?
Driscoll: In general, the Health Authorities we have met with are very supportive. For example, we have received comments from FDA noting ICHQ10 was not appropriate for a clinical QMS, and they have acknowledged the benefits of our initiative. It has also suggested examples of how a practical application would benefit organizations seeking to apply guidance. The EMA (European Medicines Agency), Health Canada, and other regulators have also provided strong support for a clinical QMS ICH guidance.