A study was conducted under the UK Regenerative Medicine Platform as part of the work of the Cell Behaviour, Differentiation and Manufacturing Hub. It comprised part of the Pluripotent Stem Cell Platform (PSCP) project funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council (grant number MR/L012537/1).

• In order to ensure market launch as quickly as possible and with judicious outlay, the process developer must reconcile two opposing needs. To ensure comparability of manufacturing process at commercial scale there must be manufacturing research sufficient to satisfy the ‘Chemical, Manufacturing and Control’ section of the regulatory application dossier. This must occur at a stage in the project cycle early enough to avoid unnecessary process re-engineering late in development. However, by no means all candidate products succeed at clinical trial and it is desirable to avoid spending money unnecessarily on process research for these putative products. The dilemma can be addressed through the careful use of three decision-making tools. The tools are illustrated in this paper using a case study of a treatment for Parkinson’s disease.

The tools that were applied

Tool 1: new product introduction map

• The tool allows the examination of the decision points in the context of the overall product development.

Tool 2: risk-based approach

• A development of the normal requirement for product and process risk analysis, this tool identifies the topics that warrant focused attention.

Tool 3: expected current value-based prioritization

• A project-specific modification of a portfolio-balancing tool, this tool allows decisions about timing of investment to be made on a quantitative basis.

Case study: Parkinson’s disease

• Parkinson’s disease (PD) is a debilitating condition that is costly to manage and control. It is of growing importance as the average age of citizens in the developed world increases.

Developing cell-based medicinal products for PD

• The characteristics of a cell-based therapeutic product candidate for PD are discussed in the context of a specific project within the UK Regenerative Medicine Platform programme.

Dopaminergic neuron process description

• The overall process is described and the challenges are described that arise from the need to ‘freeze’ the process as early as possible in a form in which the product can be made at scale to a predictable and acceptable specification. Two situations are used to show how a value-based development decision may be made: one based upon prioritizing early evidence of efficacy and the other based upon prioritizing the early evidence of process capability.

Discussion

• The application of the tools described in this paper is considered in the context of management of risks to the patient that will otherwise arise. The potential for realization of the risks is illustrated with reference to the known behavior of embryonic and induced pluripotent stem cells.

Conclusion

• The importance of brevity and focus in process development for advanced therapies is re-emphasized and the application of the tools described is placed in that context.

Future prospects

• The future of cell therapy manufacture is likely to be divided between products that require up- or out-scaling for manufacture. Robust process characterization is essential for both yet the features of the process that are relevant may differ between the two categories. Both need systematic assessment. Over time, a growing familiarity with effective techniques for focused process research coupled with a growing library of case studies will empower the user community.