Finding quality in complexity: how cellular therapeutics are shifting analytical paradigms for clinical supply and product manufacturing

Published: 14 May 2021
Vilma Jimenez Sabinina,
Vilma Jimenez Sabinina
Analytical Development and Clinical QC for Biotech Products, Bayer AG, Product Supply, Friedrich- Ebert-Straße 217-233, Bldg. 230, Room 2.205, 42117 Wuppertal, Germany
Dominic Günter Hildebrand
Dominic Günter Hildebrand
Author for correspondence: Bayer AG, Product Supply, Analytical Development and Clinical QC for Biotech Products, Friedrich- Ebert-Straße 217-233, Bldg. 230, Room 2.235, 42117 Wuppertal, Germany

Recent clinical successes of CAR-T cell approaches like Kymriah® or Yescarta® have promoted a boost of clinical trial applications for cellular therapeutics (CT). In terms of quality control, analytical strategies required to assess living cells represent a shift of paradigms compared to how chemical or recombinant biological drugs are typically addressed in a regulated GMP environment. This article elaborates on the corresponding CT-specific challenges and aims to provide standardized strategies for mitigation where available. Furthermore, a generic scheme of critical quality attributes is proposed, which takes into account largely different types of CT, including for example mesenchymal stem cells, CAR immune cells or stem-cell derived cardiomyocytes. Somewhat counterintuitively, rather few analytical core platforms (advanced GMP cell culture, flow cytometry, ddPCR, NGS and microscopy) should suffice to execute the vast majority of the corresponding analytical tasks throughout the product lifecycle. Obviously, internal mastery of these platforms should be achieved in order to ensure proper support of process development activities and product progression throughout clinical development, while other analytical tasks might be prone to be outsourced to contract research organizations.

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