Costs, challenges and opportunities of decentralised chimeric antigen receptor T-cell production: a literature review and clinical experts' interviews.

The objectives were to summarise the evidence and clinical experts' views comparing the use of decentralised produced chimeric antigen receptor (CAR) T-cell therapies versus commercially available products, regarding drug costs, time to finalised product and other reported advantages, disadvantages, challenges and facilitators. A literature review according to the PRISMA guidelines was conducted in Medline, Embase and Trip databases. Publications were included if they reported information on cost estimates, time to finalised products and other outcomes of interest of a decentralised CAR T-cell production strategy. A structured interview guide was developed and used for qualitative expert interviews. Five experts were purposively selected, and interviews were either conducted face-to-face or online, and recorded for the purpose of transcription. Transcripts were analysed and categories and codes extracted. Reporting is based on the COREQ checklist for reporting qualitative research. Costs of decentralised produced CAR T-cells appear to be lower by a factor two to 14, compared with commercial products. But there is high uncertainty about this estimate, because it is unclear whether cost components included are comparable and due to the heterogeneity of the studies. The most commonly reported advantages were proximity to patients and decreased product risks and costs, whereas the continuing dependency on centrally manufactured reagents and specific characteristics of 'fresh' CAR T-cells are reported as disadvantages. Compliance with regulatory requirements is mentioned as the biggest challenge. The availability of closed-system production devices is reported as one main facilitator, as are clear commitment, secured financing and knowledge transfer from already experienced centres. Apparent cost differences open a field for healthcare decision-makers to discuss and justify investment costs for implementation of a complementing decentralised production programme and to realise other associated benefits of such a strategy, such as flexibility, patient proximity and expanding patient access.