Regulators and industry are sitting down together to mine their experience and map out some clearer directions and expectations about what is needed to empower quality risk management (QRM) in improving the pharmaceutical quality system (PQS) and the industry/regulatory communication process at the review and inspection levels.
These discussions are taking concrete form in a number of papers and guidances from various agency, industry and academic organizations, including a revision that has begun of ICH’s 15-year-old QRM guideline Q9.
The “business plan” on the Q9 revision effort was endorsed by the ICH Management Committee in late October, 2020. Endorsement of the Q9(R1) “concept paper” followed in November.
The revision plan and paper explain that while ICH was instrumental in advancing industry and regulator understanding of QRM principles and approaches, the benefits envisaged by ICH Q9 “have not yet been fully realized.”
Highlighted are four current QRM problem areas: ● “the high levels of subjectivity in risk assessments and QRM outputs, leading to a lack of good science” ● “challenges in the management of product availability risks, resulting in continued shortages of important medicines for patients” ● “a lack of understanding of what constitutes formality in QRM, and how to apply varying degrees of formality in QRM activities so that a better use of resources can be made,” and ● “a lack of clarity on what constitutes good risk-based decision-making.”
The plan and paper explain how the Q9 revision could help in addressing these issues, leading to “more effective, robust, integrated, and science-based QRM activities within the pharmaceutical environment,” and increased harmonization around QRM’s use and implementation.
In turn, the benefits from more effective QRM strategies would include: ● significant savings in reduced quality defects and product recalls ● efficiencies from better-designed manufacturing processes, more effective control strategies, and validation activities, and ● increased ability to invest in optimizing/modernizing manufacturing processes and technologies.
The timeline included in the business plan calls for a Step 2b draft of the revision to be released in the fall of 2021, with Step 4 adoption of the final revised guideline targeted for June 2022.
The three-part story below explores the current dialogue on QRM and its interrelationship with knowledge and change management, the PQS, and the control strategy across the process and product lifecycle.
As the Q9 revision proposal indicates, the stakes are high in strengthening the effectiveness of QRM in the various roles it needs to play and how this effectiveness is communicated – particularly as the technical complexity of products and processes continues to grow. Shifting the QRM focus from “reactive to proactive,” the proposal stresses, “will enable continual improvement to become a key aspect of the PQS.”
In turn, central to the dialogue that has taken place in the ICH Q12 context is how to evolve the post-approval change (PAC) regulatory paradigm to empower rather than inhibit this proactive risk and knowledge management approach in order to realize the continual improvement goal. [Editor’s Note: IPQ has closely tracked the QRM/KM/PAC dialogue as it has evolved over the past decade. A chronological bibliography with links to this in-depth IPQ coverage is provided below.]
Part I: ICH Q9 Revision Lead O’Donnell on the Evolution of QRM
The first part of the story focuses on a presentation at a late February QRM Summit by Ireland HPRA’s Kevin O’Donnell, who is serving as lead on the ICH Q9 revision Expert Working Group (EWG). O’Donnell explored how the principles of quality risk management could be furthered in practice in conjunction with advancements in knowledge management, quality systems, and regulatory communications.
Part II: FDA’s Rick Friedman on Advancing Aseptic Processing through QRM
The second part offers insights on the relevance of current QRM concepts and practice to improving the reliability, compliance and efficiency of aseptic processing, provided by FDA CDER’s Rick Friedman at the 2021 ISPE Aseptic Conference. Friedman is representing FDA on the ICH Q9(R1) EWG, and brings CDER compliance office experience to bear in discussing how to improve aseptic processing risk management and control.
Part III: Industry/Academia Thought Leaders on the Evolving QRM/KM Relationship
The members of the Technical University of Dublin’s Pharmaceutical Regulatory Science Team have been making an important contribution to the QRM/KM dialogue through their cumulative industry experience and ongoing research in conjunction with TUD’s PhD program. The third part focuses on insights offered in March by two of the industry team members, in particular: ● Merck’s Marty Lipa at the 2021 PDA Annual Meeting, and ● Genentech’s Emma Ramnarine, in an interview conducted through the PDA-Ireland chapter.