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

Arteriocyte, Inc., Cleveland OH

Investigators

Abstract

Abstract With the rapid development of new cell-based products, and the push from regulatory bodies to move away from animal-derived products, there is an urgent need to find a scalable, high quality, and cost-effective replacement for fetal bovine serum (FBS). Despite efforts to develop inexpensive, chemically defined culture media, replicating 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 media. Our PLUS? human platelet lysate (hPL) product is poised to fulfill this unmet need. PLUS? is manufactured using expired, transfusion-grade platelets that are widely available as a waste product from blood banks. As a human-derived product, PLUS? lacks all of the bovine-derived antigens and viruses that may contaminate cell- based products produced using FBS. The use of PLUS? can lead to overall lower costs for expanding cell types such as human bone marrow mesenchymal stromal cells (hMSCs) and human adipose-derived stromal cells (hASCs), due to increased growth rates for the cells in PLUS?-supplemented medium compared to FBS. Despite manufacturing PLUS? using only platelet units that have undergone rigorous serology and infectious disease screening, contamination of the product with undiscovered and emerging pathogens is possible. Our 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 risks. The 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 performance. The 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 proliferation. The project will next evaluate the ability of varying gamma doses to inactivate an array of model viruses that could infect the platelets utilized in PLUS? manufacturing. The project will finally seek to obtain feedback on the virally inactivated PLUS? product from a range of end users actively developing cell-based technologies in the areas of tissue engineering, cellular therapy, cell expansion. This project will require collaboration with multiple organizations, including contract research organizations (CRO), contract sterilizers, and end users in tissue engineering and cellular therapies. The project will be completed within a one-year timeframe and result in a commercially available product manufactured in accordance with current good manufacturing practice (cGMP) requirements under our quality management system (QMS). The availability of a virally inactivated hPL product would help to fuel innovation in the manufacturing of next generation cellular products.