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

In the UK, the NHS spent GBP 8.3 billion on wound management in 2017/18 [1]. A significant proportion of this spending was for chronic ulcers of which diabetic foot ulcers (DFUs) are one of the most prominent. It has been estimated that around 19–34% of all diabetic patients will develop a DFU at some point during their life [2,3]. The increasing prevalence of diabetes together with a lack of successful long-term treatments for DFUs brings an urgent need to develop accessible, effective treatments.

Platelet-rich plasma (PRP) products, such as the RAPID Biodynamic Haematogel, are a novel treatment modality for various indications including topical treatment for DFUs. Rich in crucial growth factors, PRP and its gel form have been shown to aid wound healing [4]. Autologous PRP gels are prepared at the point of care (POC) and often exhibit high batch-to-batch variability due to the heterogeneity of the starting material (individual patient’s blood) and variation in manufacturing processes. Consequently, control of PRP gel manufacturing using Good Manufacturing Practice (GMP) is a critical part of quality assurance and can be achieved by adopting a quality by design approach in line with ICH Q8 [5].

In this study, RAPID Biodynamic Haematogel, a leukocyte and platelet-rich plasma (L-PRP) product, was investigated to identify putative critical processing parameters (cPPs) in gel manufacture that might require control to ensure product quality. Processing parameters that may have an impact on the final product attributes included white blood cell (WBC) content (% hematocrit) and temperature, along with filtration, time-to-thrombin use and mixing variables [5,6,7,8]. The effects of these processing parameters on two gel attributes that are reflective of gel quality and consistency were measured, (i) time to gel and (ii) exudation of releasate from the gel. A state-of-the-art design of experiments (DoE) methodology was applied to efficiently evaluate the influence of multiple cPPs on product quality [8]. While DoE has been widely applied in pharmaceutical manufacturing and bioprocess optimization [9,10], its application in POC autologous product development is novel.

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