Scalable manufacturing of human platelet lysate for next generation cell-based technologies

Abstract With the rapid development of new cell based productsand the push from regulatory bodies to move away from animal derived productsthere is an urgent need to find a scalablehigh qualityand cost effective replacement for fetal bovine serumFBSDespite efforts to develop inexpensivechemically defined culture mediareplicating the complex mix of nutrients and growth factors provided by FBS has been a huge challenge and the vast majority of cells cannot yet be successfully cultured in serum free mediaOur PLUShuman platelet lysatehPLproduct is poised to fulfill this unmet needPLUSis manufactured using expiredtransfusion grade platelets that are widely available as a waste product from blood banksAs a human derived productPLUSlacks all of the bovine derived antigens and viruses that may contaminate cellbased products produced using FBSThe use of PLUScan lead to overall lower costs for expanding cell types such as human bone marrow mesenchymal stromal cellshMSCsand human adipose derived stromal cellshASCsdue to increased growth rates for the cells in PLUSsupplemented medium compared to FBSDespite manufacturing PLUSusing only platelet units that have undergone rigorous serology and infectious disease screeningcontamination of the product with undiscovered and emerging pathogens is possibleOur preliminary studies have indicated that incorporation of gamma irradiation as a viral inactivation step would be a robust and cost effective solution to alleviate safety concerns and risksThe overall objective of this Phase I project is to identify an optimal gamma dose capable inactivating a range of model viruses without detrimentally impacting product performanceThe project will initially seek to evaluate the effects of varying gamma doses on product characteristics and performance using assays to measure the concentrations of important growth factors and assess hMSC proliferationThe project will next evaluate the ability of varying gamma doses to inactivate an array of model viruses that could infect the platelets utilized in PLUSmanufacturingThe project will finally seek to obtain feedback on the virally inactivated PLUSproduct from a range of end users actively developing cell based technologies in the areas of tissue engineeringcellular therapycell expansionThis project will require collaboration with multiple organizationsincluding contract research organizationsCROcontract sterilizersand end users in tissue engineering and cellular therapiesThe project will be completed within a one year timeframe and result in a commercially available product manufactured in accordance with current good manufacturing practicecGMPrequirements under our quality management systemQMSThe availability of a virally inactivated hPL product would help to fuel innovation in the manufacturing of next generation cellular products Project Narrative With the rapid development of new cell based productsand the push from regulatory bodies to move away from animal derived materialsthere is an urgent need to find new media supplements that are scalablehigh qualityand cost effectiveOur PLUShuman platelet lysate product is poised to fulfill this unmet needbut before this can be realizedthe safety of the product against unknown and emerging pathogens must be ensuredBy optimizing the dose of gamma irradiation to ensure viral inactivation without loss of product performancethis project will help to fuel innovation in the manufacturing of next generation cellular products