by Giuliana Miglierini
Innovative approaches to the development manufacturing and quality control of medicines are becoming the new paradigm to be faced both from an industrial and regulatory perspective. Not only innovative technologies for delivery, such as mRNA vaccines, many novel materials as well as new types of interconnected devices, wearables and digital health approaches need a particular attention to ensure the European regulatory network will be able to intercept and address gaps in the current framework. An increased predictability for developers is the final target objective.
EMA’s answer to this need passed through the establishment, in September 2022, of the new Quality Innovation Expert Group (QIG). The Group will act also as a preferential location for exchange and interaction between regulators and other stakeholders, at the European and global level. QIG is part of the Quality Domain of EMA’s working party structure; all its activities will be aligned to EMA’s Regulatory science strategy to 2025.
The eight members of the Quality Innovation Expert Group have a background in chemical, biological quality assessment and Good Manufacturing Practice (GMP) inspections. They have been nominated from the list of European experts and adopted by the CHMP and CVMP. Other ad hoc experts may be recruited were needed.
The Chair of the new group is Marcel Hoefnagel (he will also become a member of the Domain Governance); other members include Giampiero Lorenti, Leticia Martinez-Peyrat, Christina Meissner, Silke Schül, Barbara Stubbe, René Thürmer, and Marcos Timon. Further members may be appointed in future, based upon workload considerations.
The members’ selection process aims to include in the QIG two experts for each of the following areas: quality assessment for chemical medicinal products, quality assessment for biological medicinal products and ATMPs, GMDP inspections. Membership will be reviewed every three years; the chair’s appointment may be renewed only once.
The current schedule described within QIG’s provisional mandate indicates a maximum of six meetings per year (one of which face-to-face), planned to fit with Biologics Working Party (BWP), Quality Working Party (QWP) and/or GDMP Inspectors Working Group (IWG) meetings. Ad hoc meetings can also be organised as required. QIG’s work plan shall also include topics and frequency of the “Listen and Learn” platforms, while interactions with the stakeholders should be accommodated as needed, as well as meeting with other international regulators.
The technical, scientific and administrative support to the QIG will be provided by the EMA Secretariat.
QIG’s provisional mandate
The provisional mandate and rules of procedure of the Quality Innovation Expert Group was published in November 2022. The complete 2023 work plan is also expected to be published.
The main goal of the new QIG is to facilitate the translation into practice of innovative pharmaceutical manufacturing approaches, with respect to all the different range of medicinal products (i.e. chemical, biological and/or biotechnological substances, advanced therapy medicinal products).
To achieve this very ambitious task, the QIG shall be involved in many different activities, starting from the identification of innovative manufacturing approaches for pharmaceuticals and of the regulatory challenges associated with them. To this instance, possible tools to be used include horizontal scanning of emerging technologies, followed by proposals of regulatory measures to address them in the form of developing position papers, Q&A documents, etc.
Translation of innovative technologies into regulatory submissions or manufacturing and control facilities may be supported through actions at the level of scientific advice, marketing authorisation applications, related post-authorisation lifecycle changes and routine manufacturing and control operations. This objective shall be supported by the interaction with other EMA’s structures, such as the BWP and QWP Working Parties, and IWG Working Group.
Harmonisation at the European level of the approach to be used by regulators for the quality assessment of submissions and GMP inspections also falls under QIG’s mandate to operate. Attention should be paid to the advancement of regulatory sciences, by mean of a research driven agenda aimed to increase the effectiveness and awareness of the European Union as a centre for innovation, and shared between the European regulatory network and the academia.
QIG’s representatives are expected to participate to various international regulatory fora (e.g. ICH, ICMRA, PICs, IPRP) to inform about the European position and to facilitate cross-regional convergence on open issues. Existing channels and confidentiality agreements may also be used to facilitate the dialogue between the Group and other international regulatory partners on product- specific or technology-specific topics. Outcomes from QIG’s activities will be reported to the Quality Domain Governance, EMA Committees and Working Parties as needed.
The main initial tasks
The provisional mandate lists the points to be addressed by QIG’s experts as the first tasks for new new-born group. Acting as an entry point for developers to discuss new approaches along the entire life cycle of innovative medicinal products is a main one, to be declined by QIG on technology only. Continuity with other dialogue pathways already put in place by EMA should be pursued through the participation of a QIG member to the primary assessment as part of the (Co)-Rapporteur team or alternatively, as CHMP peer reviewer.
Emerging technologies that might impact regulatory decision making in the medium to long term represent another QIG’s priority; their assessment may be performed also with engagement of ad hoc experts and academia.
QIG members may support the Quality Domain Governance with recommendations on the quality and GMP requirements of medicinal products (e.g. data requirements and expected regulatory impact of analytical technologies, control strategy approaches, devices, drug delivery systems, materials, manufacturing technologies and novel facility designs for active substances and finished products – including continuous manufacturing and decentralised manufacturing-, digitalisation). The implications for the regulatory and supervisory system of the implementation of innovative quality and manufacturing technologies may also be addressed.
The QIG group may contribute to the preparation, review and/or update of quality position papers and guidance documents, in collaboration with the BWP, QWP and/or GMDP IWG, as well as to the training and quality-related workshops for EU quality assessors and GMP inspectors. Harmonisation of efforts within the entire EMA’s and Heads of Medicines Agencies (HMA) structures shall be enabled by the interaction with EMA’s ITF/Innovation Office/SME Office and the HMA Innovation Office. Communication with the external stakeholders (including the industry, academia and regulators) shall be supported by the creation of a dedicated set of communication platforms.