TransCelerate’s Clinical Quality Management System: From a Vision to a Conceptual Framework

Abstract

The Quality Management System (QMS) initiative of TransCelerate BioPharma Inc has identified potential benefits that could be captured from the development of a flexible, proactive clinical QMS conceptual framework for clinical research. Such a framework would aid organizations in seamlessly managing the complex clinical trial environment and, ultimately, in expediting delivery of needed treatments to patients. This article chronicles the evolution of a TransCelerate concept paper describing a proposed clinical QMS framework and reviews feedback from varied global clinical trial stakeholders during socialization of the concept paper. Many stakeholders recognized the potential for the concept paper to inform development of a harmonized International Council for Harmonisation (ICH) guideline, providing needed clarity from regulators on their expectations for QMS in the clinical realm. Accordingly, the article also describes TransCelerate's efforts to work with regulators to facilitate harmonization on this important topic and reviews ongoing work to develop additional tools and resources that may support organizations in evaluating whether and how they might translate the conceptual framework principles into practice. KeywordsTransCelerate, QMS, clinical development, risk management, issue management, knowledge management, clinical quality IntroductionOrganizations engaged in drug development face an increasingly challenging environment: an expanding global footprint for clinical trials, evolving regulatory requirements, dynamic partnership models, and rapidly evolving technology. At the same time, many organizations are also innovating how trials are designed and conducted, adding to the complexity. Managing this complexity could be greatly enhanced by an effective and efficient Quality Management System (QMS). However, what constitutes an effective and efficient QMS is not well defined for clinical development. This article provides an update on the activities of a TransCelerate initiative developing a flexible, holistic, clinical QMS conceptual framework to address this gap. Initial Development of a Vision and Outline for a Clinical QMS Conceptual FrameworkThis TransCelerate effort started with identifying the gap in regulatory guidance for clinical trials. Prior to this, many organizations had been attempting to implement the International Council for Harmonisation Guidance Q10 (ICH Q10) for Good Manufacturing Practices (GMP), 2 or to follow other international standards dedicated to quality, such as ISO methodology.3 None, however, suited the unique circumstances of clinical trials. This issue, and other related quality issues, led TransCelerate to work to develop a vision and outline for a clinical QMS conceptual framework.1 This outline incorporated feedback from TransCelerate member companies on their existing clinical QMS, perspectives on QMS from other nonpharmaceutical industries, and key concepts (ie, risk-based thinking) from the revised International Organization for Standardization 9001 sta...

Evaluation of opportunities for the use of modern methods for correction and prevention of risks in the quality control of clinical trials

“…CT QMS according to Meeker-O'Connell et al includes a combination of senior management development and quality assurance, compliance with standards, understanding of consumer needs, compliance with policies and procedures, adequate training, implementation of quality control, use of risk-based monitoring and audits, the existence of a strict corrective and preventive action policy, as well as ensuring a continuous improvement process [8].…”

“…The analysis of the selected publications showed (Table 1) that the key issues highlighted in them were the study of factors that determine the need for implementation of QMS in CT, the establishment of an effective system of quality management that operates at all stages of organizing and conducting of CT, management of non-conformances within the framework of the CT quality management concept, application of the Quality-by-Desing concept for quality management during organizing and conducting of CT, as well as the benefits of using risk-based monitoring [4][5][6][7][8][9].…”

TransCelerate’s Clinical Quality Management System: Issue Management

“…Establishing thresholds (eg, predefined tolerance limits) [1][2][3] for action Documentation requirements consistent with the level of impact Communication plan (including, but not limited to, notification and escalation to drive actions and accountability for appropriate levels of management) Corrective and preventive action (CAPA) management Trending and analytics requirements (including identification of stakeholders) This process will enable the end-to-end management of issues within the clinical development enterprise.…”

“…The value of trending and analytics is realized as identified risks are transformed into actionable recommendations through appropriate risk assessment. 1 The recommendations and learnings from such analyses can then be shared and embedded within an organization's risk management strategy.…”

“…Issue management is one of the elements of the Trans-Celerate clinical quality management (QMS) conceptual framework. 1 This manuscript lays out key concepts for defining, developing, establishing, and building a foundation and strategy for effectively addressing and separating issues as described above. This principled approach is grounded in proactivity, agility, sustainability, and progressive thinking.…”