A Design of Experiments Approach to Identify Critical Processing Parameters for Manufacture of an Autologous Platelet Gel for Diabetic Foot Ulcer.

Background/Objectives: RAPIDTM Biodynamic Haematogel is a platelet-based gel for wound healing in diabetic foot ulcers. This study aimed to identify the processing parameters that impact on the quality of this autologous point-of-care manufactured product. Methods: An innovative design of experiments (DOE) approach utilizing a split-plot factorial design and linear mixed-effects models enabled the evaluation of six processing parameters on time to gel and the exudation of gel releasate. Results: Across all manufacturing conditions, time to gel was 181.3 ± 179.2 s (n = 28) and the total mass of releasate exuded in 2 h was 5.6 ± 2.1 g (n = 28). Two processing parameters (temperature 15-30 °C and pre-mixing of ascorbic acid and L-PRP) had a significant impact on releasate exudation and/or time to gel. The other processing parameters (time-to-thrombin use, mixing time, WBC content and filtering of the thrombin) had little effect. The amount of releasate exuded was affected by the interaction of the temperature and time-to-thrombin use. Time to gel was affected by the mixing time and by pre-mixing the ascorbic acid and L-PRP in conjunction with temperature. Conclusions: This study illustrates an optimization of DOE methodology to inform pharmaceutical product development and identify factors that influence variability in the RAPID Biodynamic Haematogel product.