Challenges and opportunities in the manufacture and expansion of cells for therapy

ABSTRACT

Introduction: Laboratory-based ex vivo cell culture methods are largely manual in their manufacturing processes. This makes it extremely difficult to meet regulatory requirements for process validation, quality control and reproducibility. Cell culture concepts with a translational focus need to embrace a more automated approach where cell yields are able to meet the quantitative production demands, the correct cell lineage and phenotype is readily confirmed and reagent usage has been optimized.

Areas covered: This article discusses the obstacles inherent in classical laboratory-based methods, their concomitant impact on cost-of-goods and that a technology step change is required to facilitate translation from bed-to-bedside.

Expert opinion: While traditional bioreactors have demonstrated limited success where adherent cells are used in combination with microcarriers, further process optimization will be required to find solutions for commercial-scale therapies. New cell culture technologies based on 3D-printed cell culture lattices with favourable surface to volume ratios have the potential to change the paradigm in industry. An integrated Quality-by-Design /System engineering approach will be essential to facilitate the scaled-up translation from proof-of-principle to clinical validation.

KEYWORDS:

• 3D printed cell culture lattice
• cell therapy
• cost-of-goods
• meltelectro-spinning writing
• norms
• quality-by-design
• systems engineering
• T cells
• translation

Article highlights

• Laboratory-based cell culture methods rely on expensive manual processes and reagent usage is seldom optimised.

• COG needs to be affordable and will require some level of automation and optimisation of media and growth factors be included in the scale-up process.

• Technical and economic push/pull drivers are already providing the impetus for translation from proof-of-principle to clinical validation and standardization.

• Collaboration is an imperative during the early preclinical phase of product development to bridge the gap between research and commercialization.

• The manufacturing process must be underpinned by a suite of validated standard operating procedures, testing and controls to ensure that it meets the standards of GMP for human therapies

• New cell culture technologies based on 3D-printed cell culture lattices with favourable surface to volume ratios have the potential to change the paradigm in industry

This box summarizes key points contained in the article.

Declaration of interest

EM De-Juan-Pardo, FM Wunner and JH Maartens, DW Hutmacher, SC Barry and A Simula are all members of CTMCRC while EM De-Juan-Pardo, FM Wunner and JH Maartens are also holders of a CTMCRC grant. NH Voelcker is a former member of CTMCRC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript is sponsored by the Cooperative Research Centre for Cell Therapy Manufacturing (CTMCRC).