Meeting Lot-Size Challenges of Manufacturing Adherent Cells for Therapy

TLDR

Adherent cells such as MSCs and hPSCs must be produced in lot sizes ranging from billions to trillions, yet current two‑dimensional culture platforms only support about one log of expansion and are labor‑intensive with limited scale‑up potential. The study seeks to evaluate planar, packed‑bed, and suspension platforms for their capacity to meet large‑scale lot requirements and to preempt downstream processing bottlenecks. The authors compare planar technologies, packed‑bed systems, and suspension microcarrier or aggregate cultures, and propose large‑volume downstream processing solutions to enable scalable production.

Abstract

Adherent cells such as adult primary cell lines and human multipotent (MSCs) and pluripotent stem cells (hPSCs) present a manufacturing challenge as lot sizes increase from 109 (billions) to 1012 (trillions) cells (1). Typically, manufacturing platforms are good for one log of expansion. So new methods will be required to achieve commercially relevant lot sizes. Traditional two-dimensional culture methods have been used to grow anchorage-dependent cell types. Although such methods are reliable and well defined, they are very labor intensive and limited in scale-up production potential by the available growth surface area (Table 1). Allogeneic “off-the-shelf ” therapies based on adherent-cell platforms may require manufactured lot sizes from 100 billion to a trillion cells depending on a given indication’s market size (2). Here, we examine the three platforms available for producing adherent cells — planar technologies, packed-bed systems, and suspension platforms such as microcarriers and aggregate cultures — for their potential of meeting lot requirements at different scales. As new production methods are introduced, we propose addressing downstream processing bottlenecks before they occur and introduce some large-volume downstream process technologies.