Manufacturing Living Therapies
Enabling “next-generation” drugs through automation and standardization
Cell and gene therapy continues to drive biopharmaceutical investment and pipelines, despite COVID-related research and clinical trial disruptions. Last year, the global cell therapy market size was $7.8 billion, expanding annually by almost 15% in the next 8 years, according to Grand View Research, a market research company. Add in that global pipelines from CAR-T based therapies alone increased by 50% from 2019 to 2020 and you have the makings of an enormous industry willing and able to tackle some of the most challenging human ailments.
The problem with living therapies is that they are alive
In order for cell and gene therapies to reach their potential, unsustainably high manufacturing costs must be addressed. Factors often considered include consumables, quality control, and a highly skilled labor force. Recognizing that no single entity has the resources to innovate every step in the process, several companies have stepped in to offer unique approaches, ranging from software to instrumentation. Emphasizing automation solutions can simultaneously satisfy strict quality control metrics through increased precision and reduced variation between batches, as well as temper expensive hands-on time.
Simply automating processes alone is insufficient towards democratizing cell therapies, until those processes themselves become standardized. Advanced therapies require numerous assays and analytical readouts from donor material characterization to manufacturing quality control . Often protocols and metrics may vary across companies, geographies, or even among individuals, keeping costs high and creating headaches for scientists and regulators alike. Important steps are being taken to standardize methods and streamline the product characterization that is so vital to the success of living therapies.
Towards standardizing flow cytometry
Given the “cell” in cell therapy, flow cytometry is considered an essential analytical tool by labs worldwide. For instance, Charles River Laboratories Principal Scientist III Christoph Eberle, Ph.D. runs the flow cytometry facility at his site in Worcester, Massachusetts, specializing in preclinical pharmacology for clients in cancer immunotherapy. With an eye towards improving cell recovery, reproducibility, and workflow of increasingly difficult to isolate tumor infiltrating lymphocytes from murine tissues, Dr. Eberle turned to Laminar Wash technology from Curiox Biosystems to semi-automate flow cytometry sample preparation. He now uses the methodology to standardize flow cytometry processes in his lab, such as evaluating debris removal kits and identifying whether certain cell subpopulations are real or artifacts.
When it comes to “reducing and eliminating sources of human error and bias” from flow cytometry workflows, “many of us eventually hear the phrase ‘garbage in, garbage out’ to emphasize the relevance of how well samples should be prepared,” Dr. Eberle said in a recent webinar hosted by the flowcytometry UK society. “That is why we are exploring a next-generation technology.”
“Since adopting Laminar Wash technology, it has helped us streamline our sample preparation procedure for tumor microenvironment characterization by flow cytometry. Through automation, we can simplify washing steps in immunostaining protocols to save time. By minimizing variabilities introduced through human error, we observe better staining results in terms of reproducibility and data quality,” concluded Dr. Eberle in the webinar.
Putting automation solutions to the test
While Laminar Wash technology has proven beneficial in characterizing preclinical models, how can it address standardizing cell therapy manufacturing workflows? Currently, initiatives are underway to unify flow cytometry methods nationally and across Europe. The National Institute of Standardization and Technology (NIST) launched the Flow Cytometry Standards Consortium in February with the mission of “[developing] measurement solutions and standards in flow cytometry to improve confidence, establish traceability, and enable comparability,” a keystone for widespread adoption and scaling of cell therapy product development.
Consortium technical lead Lili Wang, Ph.D. identified “the lack of reproducibility and comparability of results across various flow cytometry platforms” as major challenges facing advanced therapy development. By bringing together expertise across industry, academia and government, the Consortium aims to overcome these roadblocks through the “[development of] measurement solutions, standards, and best practices for flow cytometry.” (1)
“By minimizing variabilities introduced through human error, we observe better staining results in terms of reproducibility and data quality.”
-Dr. Christoph Eberle, Charles River Laboratories
To this end, Curiox recently announced its membership in the Consortium, contributing expertise and its AUTO1000 system, a fully automated platform to prepare cells for flow cytometry. Together with NIST scientists, Curiox plans to convert common cell assay protocols into standardized, hands-free and walkaway workflows that are easy for training new users and materialize the benefits of automation.
Incremental improvements focusing on process standardization through automation are crucial for next-generation therapies to become mainstream. Bringing down costs and proving product quality and safety are key to the widespread adoption of such therapies for the patients who desperately need them.
By Geoffrey Feld, Ph.D.
Marketing & Content Manager, Curiox Biosystems
1 Wang, Lili, PhD, “Flow cytometry standards are needed to ensure effective diagnosis and treatment” BioPhotonics, July/August 2021