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  1. Advancing Regulatory Science

Engineering quality control into biomanufacturing of extracellular vesicle-based products

CERSI Collaborators: Steven M. Jay, PhD, University of Maryland-College Park

FDA Collaborators: Steven R. Bauer, PhD, CBER

Project Start Date to End Date: May 29, 2020 – January 25, 2022

Regulatory Science Challenge

Extracellular vesicles (EVs), including exosomes and other subtypes, have emerging commercial potential for use as cell-derived therapies - this would require FDA to develop a strong science-based regulatory approach. EVs are small lipid sacs released from cells that transfer material to other cells. Over 150 clinical trials involving EVs are ongoing as of May 2020 (clinicaltrials.gov), yet there are currently no quality control standards for the manufacture of EVs that would enable validation of a potential commercial product. The goal of this project is to fill this gap related specifically to mesenchymal stromal cell (MSC)-derived EVs, which are heavily cited in the academic literature as useful for a variety of therapies and are currently being studied in several clinical trials. MSCs are cells capable of becoming several different cell types.

Project Description and Goals

MSC EVs are associated with many different positive effects on health, with one of the most important being anti-inflammatory properties. In this project, we will first assess whether EV anti-inflammatory activity can be predicted based on the appearance of the EV-producing MSCs. This will be done by comparing microscopic analysis of MSCs to performance of EVs in reducing inflammatory secretions of relevant cell types, such as macrophages. Macrophages are blood cells that remove foreign material or organisms. To confirm this, we will generate scaffolds to control MSC morphology and assess outcomes of MSC EVs. Overall, this study will attempt to establish proof-of-concept that monitoring and controlling MSC morphology can be employed for quality control of MSC EVs.

Research Outcomes/Results

Microfabricated (miniature) devices were generated to confine MSCs into an elongated morphology (visual appearance of the cell). The EVs produced by these elongated MSCs were found to have increased anti-inflammatory properties. Thus, the premise that MSC morphology can be used as part of quality control for MSC EV production has been established.

Research Impacts

These outcomes could inform FDA’s regulatory decision making related to developing quality control parameters for MSC EV production. The results of these studies will be disseminated through peer-reviewed publication.


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