The UK’s emerging regulatory framework for point-of-care manufacture: insights from a workshop on advanced therapies

Abstract

Point-of-care (POC) manufacture can be defined as the production of therapies in clinical settings or units close to hospitals and patients. This approach is becoming increasingly viable due to the emergence of flexible manufacturing technologies. Expecting an increase in this kind of production, the UK's regulatory agency, the Medicines and Healthcare products Regulatory Agency (MHRA) is proposing a regulatory framework specifically designed for POC manufacture. To discuss the challenges of POC manufacture and the MHRA's proposal, the EPSRC Future Targeted Healthcare Manufacturing Hub (FTHMH) organized a workshop drawing insights from specialists in cell and gene therapy manufacture. Through presentations and discussion roundtables, the workshop highlighted the challenges for the UK and other countries implementing POC manufacture. The workshop attendees stressed four main issues: quality control; standardization and equipment use; availability of qualified personnel; and the challenges to be met by hospitals participating in POC manufacture systems. This commentary provides a summary of the points discussed in this workshop.

Polish regulatory system regarding ATMP hospital exemptions

“…Together, these four countries are a good illustration of the interplay between unifying concepts versus national differences in the way ATMP-HE are managed in different healthcare systems. Footnotes to Table 5 cite the breakdown of these parameters in previous studies of ATMP-HE practices in Europe ( 3 – 15 ). It is worth pointing out that many aspects of healthcare in general are not fully harmonized at the EU level.…”

“…To date there is no full harmonization of ATMP-HE regulations among EU countries, beyond the overall guidelines provided in the original EU regulation that created ATMP-HE ( 2 – 15 ). We have demonstrated that the Polish implementation of the EU directive is within the mainstream of practices among EU countries regarding manufacturing of products and management of ATMP-HE programs.…”

“…One source of creative tension in the application of the ATMP-HE pathway is that each EU member country has developed their own method of interpreting and applying the ATMP-HE regulations. As a result, the landscape of what therapies are covered by ATMP-HEs and how these treatments are offered may differ significantly from one country to another, as previous authors have noted ( 3 – 15 ). Studies of the sociology of science have pointed out that scientists and regulators may feel pressures to modify universal standards to their own national circumstances, either because of a need to adapt to local realities like pre-existing practices, or out of a desire to be competitive with other nations ( 16 – 18 ).…”

“…Studies of the sociology of science have pointed out that scientists and regulators may feel pressures to modify universal standards to their own national circumstances, either because of a need to adapt to local realities like pre-existing practices, or out of a desire to be competitive with other nations ( 16 – 18 ). Some members of the cell and gene therapy (CGT) community have argued that the ATMP-HE regulations in various countries should be more harmonized ( 5 , 13 , 14 ), whereas others feel that the current system encourages innovation, localization, and cost savings ( 10 , 12 , 15 ).…”

Retrospective Analysis of Autologous Chondrocyte-Based Cytotherapy Production for Clinical Use: GMP Process-Based Manufacturing Optimization in a Swiss University Hospital

“…Specifically, due to the autologous nature of many of these cell-based products, process-related adaptations have been made to the ad hoc manufacturing workflows, to optimally account for the short shelf-life and the volatile nature of the processed biological materials [16]. Due to burdening temporal and logistical constraints, several initiatives for point-of-care manufacturing of cell-based therapeutic products have emerged, which imply small-batch processing and multi-professional specific expertise [17]. Alternatively, several cost rationalization drivers have led to the emerging technological transition toward mobile infrastructures and automated bioreactor systems, for the insurance of both flexibility and efficiency of the GMP-compliant cell production [18][19][20][21].…”