Cell and Gene
The cell and gene therapy (CGT) sector is grappling with multiple challenges in the post-pandemic era. Despite a partial recovery this year, the financial landscape remains difficult, further strained by limited R&D advancements, insufficient business analytics, and lack of customized platforms suited to CGT demands.
Industry experts in conversation with BioProcess Insider at Biotech Week Boston (BWB) 2024 noted a significant industry-wide dip in investments post 2020. The decline was especially pronounced for CGTs, moving away from previous investment approaches.
From “2015 to 2019 there was a big, wild, wild west investment approach to CGTs. Everybody wanted to get in. Money was flowing very well,” said Renee Hart, chief business officer (CBO) of cell analysis tech firm LumaCyte.
“At the time”, she continued, “the challenge was – the industry’s unfamiliarity with the biological effects of these products, their potency in process development and manufacturing, along with their clinical outcome. This hurt the industry dramatically.”
Drawing parallels to innovation in other modalities, Olivier Loeillot, the recently installed CEO of bioprocess vendor Repligen, emphasized the need to learn from the past.
“During the early 2000s, peptides, particularly oligonucleotides, and antibody drug conjugates (ADCs) were branded as a revolution. But then there came a dip right after the first three to four years because the industry realized it was more complex than what they saw. There were a ton of challenges in terms of R&D, making the economic model viable for the pharma companies, regulatory constraints, etc.” he told attendees.
“But look at ADCs now. What's happening in [CGT space] is similar to what happened in the past with ADCs, which are starting to pick up. We're now probably going to see this one climbing for the next five to ten years. I think the same is going to happen with CGTs.”
The panelists agreed that, unlike other modalities like monoclonal antibodies (mAbs), which have benefited from years of established manufacturing practices, CGTs face challenges because a one-size-fits-all approach is inapplicable here.
As Loeillot explained, “The industry must go from being non-customized to customizing every single product. What is needed is to have a common platform for your products that is going to be 80 - 90%, and the remaining 10% can be customized as per the requirements.”
Analytical needs
Another challenge highlighted by the panelists was the lack of robust analytics due to which early-stage developers were often ill-prepared to measure potency and clinical relevance of their therapies.
Hart said, “It's actually very sad, because I don't think CGT developers [in the past] would have failed if they had better analytics – if they could understand the business outcome above and beyond viability and cell count.”
Using the allogeneic cell therapy space as an example, she explained, “The market was hurt very badly. It witnessed a 50% to 70% failure rate in manufacturing because healthy donors had variabilities, despite being young and meeting all the questionnaire requirements for inclusion, two out of five therapies [using the donor data available], would be the successful in manufacturing therapies for patients.”
- AAV market is growing, with more than twice approvals in the recent 5-year period than the previous
- Old and emerging manufacturing challenges if unsolved could hinder the full potential of AAV
- The industry participants working together is the best path forward for patients
Jerry Keybl serves as Avantor's Vice President of Biopharma Product Management. He is responsible for driving integrated product strategy and execution in the Biopharma Production business for both traditional and novel modalities. Previously, he held a number of product management, marketing and strategy roles at MilliporeSigma with a repeated focus on cell and gene therapies. He also served as a Project Leader at the Boston Consulting Group (BCG). He holds a PhD from MIT in Chemical Engineering and two undergraduate degrees from the University of Pennsylvania in Chemical Engineering and Finance.
CeTechnology Transfer of Cell Therapy products into Good Manufacturing Practice (GMP) operations is a critical step in the commercialization of advanced therapeutic products. The process involves meticulous planning and coordination across multiple departments including development, Manufacturing Operations (including Quality Control), Quality Assurance and Regulatory-CMC. Herein we will discuss elements regarding facility set-up, documentation, process and analytical transfer strategies whilst considering project management do’s and don’ts form the viewpoint of ATMPs. Consideration will be also taken for both early and late phase products not only as a transferring site but as a CMO partner whilst considering various health authority requirements.ll Line Engineering technologies lead to diverse novel Novartis Host Cell Lines. Choosing the appropriate host cell line as a starting point and combining it with novel vector designs provide a robust and flexible toolbox to express various biological formats. Using small scale upstream development processes together with early selection technologies allow a quicker assessment of key clone characteristics (productivity, genetic integrity, and stability). Taken together, Cell Line Generation timelines can be accelerated by reducing clone screening efforts whilst maintaining high product quality.
Stuart’s PhD and post-doctoral studies focused on Molecular Virology and Gene Therapy applications. Stuart has worked in QC GMP operations as a service provider as well leading the commercial ramp-up of Kymriah (first to market CAR-T product). Stuart has had multiple tenures in technical research and development focused on analytical method development and CMO oversite. Stuart currently leads a manufacturing sciences and technologies group focused on transferring products into regulated GMP manufacturing operations.
Designing a production facility for gene therapy reagents requires meticulous planning to meet the quality and customization demands. Few facilities support the flexibility required nor meet the GMP standards for the small-scale manufacture of made-to-order products where sterility, process flow, and layout are critical. Learn how Teknova built their new, modular ISO 13485-certified facility to meet the rigorous demands of GMP-grade reagents for gene therapy development and commercialization.
Nicky Young joined Teknova’s Quality organization as the Senior Director of Sterility Assurance in 2022, where she has been instrumental in the building and validation of their new GMP facility. Nicky has been heavily focused on the certification of the cleanroom in accordance with ISO 14644 standards, including EMPQ, smoke studies and disinfectant validation, the microbial contamination control strategy, as well as developing the media fill, aseptic training, environmental monitoring, trending, and cleaning and disinfection strategies and programs. With more than 28 years of experience in sterility assurance and aseptic pharmaceutical manufacturing, Nicky has worked across at numerous pharmaceutical companies, ranging from CSL Behring and Baxter International to Patheon and GE Healthcare. She has also worked at large CDMOs where she was responsible for 15 manufacturing lines across two different sites, averaging 15 audits a week, and has overseen the quality of the manufacture of a variety of products, ranging from vaccines to sterile eyedrops to injectables and wound dressings.
