ICMRA Workshop on Decentralised or Distributed Manufacturing

Background

The development of innovative manufacturing and analytical technologies offers the potential for the decentralisation of manufacturing facilities, including point of care (PoC) manufacturing. This is an important area with a number of potential applications such as facilitating the production of effective treatments for individual patients or groups that are underserved by traditional large-scale manufacturing models (e.g., paediatrics, rare diseases), addressing challenges associated with the production of medicines with a very limited shelf-life and enabling more ‘on-demand’ manufacturing via manufacturing units that assist in making the supply chain more resilient, and responding to increased demand or emergency situations. 

Effective and appropriate regulatory oversight of decentralised or distributed manufacturing, collectively described by using the term DM, may also lead to changes to some established regulatory tools and approaches applied to established large-scale manufacturing facilities.  Many regulatory authorities are currently considering the optimal approach to the regulatory oversight of DM and, with this in mind, ICMRA organised a workshop to share findings and experiences among regulatory authorities to date and to help facilitate the greatest possible alignment in this area.

 

Overview of the Workshop

The workshop was held in virtual format on Tuesday 3rd December 2024. Following the opening remarks from Yasuhiro Fujiwara, ICMRA vice chair, PMDA, Naoyuki Yasuda of the PMDA provided an introductory presentation, outlining overview of the background to the workshop and the objectives of the workshop which were to:

  • Establish a common understanding of terminology of DM
  • Share experience of ICMRA members
  • Recognise regulatory and technical challenges in DM including PoC manufacturing and consider possible approaches to address them
     

The main part of the workshop was divided into three main sessions.

Session 1 was chaired by Adam Fisher from the US FDA and focussed on terminology and definitions associated with DM. During this session a number of ICMRA members provided an overview of working definitions that they were developing associated with DM, which, where appropriate, took into account engagement with stakeholders. The potential benefits associated with DM were discussed and acknowledged.

In session 2, which was chaired by Ian Rees from the MHRA, the focus turned to GxP aspects. It was noted that the application of DM would have implications for Good Manufacturing Practice (GMP) but also potentially for other areas such as Good Clinical Practice (GCP) and Good Pharmacovigilance Practice (GPvP). There was a discussion in relation to potential models for the regulation and inspection of manufacturing sites applying DM approaches and the key roles and responsibilities of any central site overseeing the operations of DM sites. The importance of collaboration between GXP inspectors and quality assessors and engagement with a range of institutions and other national regulators was emphasised for the effective implementation of DM. There was also discussion on the potential greater use of digital technologies to enable enhanced control strategies.

Session 3, which focussed on Chemistry, Manufacturing and Controls (CMC) aspects, was chaired by Marcel Hoefnagel, the chair of the Quality Innovation Group at EMA. This session considered a number of important CMC considerations associated with the application of DM approaches including the need to ensure the comparability of the product and process at all sites by appropriately controlling potential sources of variability. Enhanced product development and control strategies can facilitate the implementation of DM. Post-approval change management was also considered particularly the approach to the addition of new manufacturing sites. Existing tools (such as post-approval change management protocols) could be used where possible and appropriate, but it was also noted that some changes to existing quality assessment approaches may be needed to facilitate DM.

 

Summary and Conclusions

Finally in a summary session Johanne Veenstra from Health Canada and Laurence O’Dwyer from the HPRA provided an overview of each session and possible next steps. The potential benefits associated with DM were noted as was the need to ensure appropriate regulatory approaches that would allow those benefits to be realised while ensuring that quality standards are maintained. 

The opportunity to share experience ensure the maximum possible alignment of regulatory approaches related to DM from an early stage was noted and the following topics were identified as requiring further discussion and consideration: 

  • Key terminology and definitions associated with DM
  • Where appropriate, justification for the use of DM and PoC manufacturing approaches
  • Approach to the regulatory oversight and inspection of DM sites
  • Roles and responsibilities of a control site overseeing the activities of DM sites
  • Need to ensure process and product comparability at all DM sites
  • Impact on product testing and release processes
  • Approach to post-approval change management such as the addition of new DM site
     

It was agreed that where possible existing tools and approaches could be used and that the use of existing fora such as ICMRA, the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) to encourage alignment in this area could be considered.

A number of the participants in the workshop had engaged with stakeholders to inform the development of their approaches to the regulation of DM. The importance of continuing such engagement to help inform the development of such approaches was acknowledged.