EMA’s “toolbox guidance on scientific elements and regulatory tools to support quality data packages” for priority medicines targeting unmet medical needs, released in April 2022, reflects extensive stakeholder input and will evolve further as experience and learnings from the pandemic are evaluated.
Developed as an outcome of the 2018 joint EMA/FDA workshop on quality support to Priority Medicines (PRIME) and Breakthrough Therapy (BT) designated products, the guidance outlines the tools available in the EU to address the challenges in generating robust quality packages under accelerated conditions. It is applicable to small molecules, biological/biotech products, and advanced therapy medicinal products (ATMPs).
The guidance was drafted, consulted on, and revised throughout the COVID pandemic.
Initial consultations were held with the biologics, quality, inspection and advanced therapy working groups at EMA (BWP, QWP, IWG and CAT respectively) between September and December 2020.
Following a public consultation period from February to July 2021 – by which time a number of vaccines had undergone accelerated development – the revised draft was reviewed again by the expert committees in early 2022 and published in April.
Comments on the document were received from nine organizations, including the International Society for Pharmaceutical Engineering (ISPE), BioPhorum, the Alliance for Regenerative Medicines (ARM), the European Federation of Pharmaceutical Industries and Associations (EFPIA) and Vaccines Europe. EMA’s overview of the comments and responses to them runs to 117 pages. [Links to the final guidance and EMA’s overview of the comments are provided in Part I.]
At a session focused on an “efficiency toolbox for development and lifecycle management” at the CASSS CMC Europe Strategy Forum held in Bruges, Belgium in mid-October, regulators and industry representatives shared their collective experiences and learnings in applying flexibility tools from a regional and global perspective. The story below explores the knowledge sharing and dialogue at that session.
● Part I: EMA Perspective on its Toolbox Guidance and OPEN Initiative
In the first part of the story, EMA’s Quality Office Head Veronika Jekerle discusses her team’s perspective on the development, use, and future direction of the agency’s toolbox guidance in the context of: ● prior knowledge ● flexibilities used for COVID vaccine lifecycle considerations, ● and EMA’s collaboration with other regulatory agencies and globally with WHO.
Jekerle addressed the industry comments on the draft guidance and the criteria that led to successful interactions, approvals and proactive lifecycle management using post-approval change management protocols (PACMPs). In the final part of her talk, she explained the “Opening our Procedures at EMA to Non-EU authorities” (OPEN) procedure and the significant impact it has had on vaccine approvals in low- to middle-income countries.
● Part II: Industry View on Efficiency Tools and CMC Flexibility Learnings from COVID
The second part of the story provides industry perspectives on the challenges and solutions in accelerated CMC development.
At the CASSS session, BioMarin’s David Kirke shared a case study on setting acceptance criteria based on limited batch data in the face of regulatory expectations. Seagen’s Kavita Aiyer discussed a BioPhorum proposal for use of QbD and ICH Q12 tools for enabling efficient second sourcing of raw materials and provided a case study on applying QbD principles to determine “critical material attributes” and “target material profiles” for virus filters. AstraZeneca’s Mark Pellett then shared the lessons learned from the accelerated development, manufacture, and distribution of the AZ COVID-19 vaccine, Vaxzevria, and how the EMA toolbox was successfully utilized.
● Part III: Panel Discussion on Effective Tools for the Future
A panel discussion followed the individual presentations, during which the CMC flexibility challenges and opportunities were further explored – with the managing of post-approval changes in a global context receiving particular attention. The speakers were joined in the panel by AGES’ Ilona Reischl and CDER’s Chana Fuchs. Participating from the audience were European industry and regulatory agency thought leaders involved in key CMC global initiatives.
Among the subjects covered during the discussion were: ● prior knowledge and acceptance criteria for rare disease drugs ● lifecycle management of pandemic products ● taking a proactive approach to QbD for raw materials, and ● strategies for global alignment. A review of an industry paper on product sameness and a regulator proposal for a global product quality knowledge management system (PQ KMS) as foundation blocks for regulatory reliance is included.
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