There are often issues associated with challenging accepted working practices through the introduction of statistical tools. This paper outlines common objections to the use of DOE (design of experiments) and our standard responses to overcome these obstacles.

Experimental design (Box, G. E. P.; Hunter, W. G.; Hunter, J. S. Statistics for Experimenters; Wiley: New York, 1978 and Carlson, R. Design and Optimisation in Organic Synthesis; Elsevier: Amsterdam, 1992) is an established and proven methodology for product and process improvement in the pharmaceutical industry. This paper presents a step-by-step approach to optimisation of a synthetic transformation using a central composite experimental design, in conjunction with automated on-line HPLC. Highly predictive models for the reaction were obtained using a commercially available software package. [There are many commercially available DOE packages. The software package we used was Design-Expert 5 (DX-5) ().] These mathematical models were interrogated to examine the effect on yield and quality under a variety of reaction conditions or constraints. The synergy of experimental design and automation is also discussed.

Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment.