How CDMOs Have Become Emerging Technology Influencers
Tatiana Nanda, Head of Cell Therapies PD, Drug Product and Nikhil Tyagi, Director of Cell Therapy Process Development
The science behind advanced, cell-and-gene-based drugs is developing rapidly, opening new opportunities for targeted, highly effective therapeutics. Around the world, companies are currently researching thousands of these lifesaving drugs. However, manufacturing them on a large scale presents logistical challenges that often result in a slow, costly process.
Unlike chemically based drugs, cell-and-gene therapeutics may require a complex scale-up strategy, progressing from preclinical research to clinical trials and ultimately to commercial manufacturing. These technological challenges can delay the entire drug development process and reduce companies’ return on investment (ROI). However, contract development and manufacturing organizations (CDMOs) are uniquely positioned to solve this problem. As emerging technology influencers, they fill the gap between cutting-edge science and the commercial sector by partnering with the best technology providers to maximize the manufacturing process.
CDMOs Offer Flexibility Through New Technologies
Pharmaceutical companies often prioritize their capital investment to develop new indications and modalities, so when they invest in manufacturing, they are frequently focused on a single platform. Investing in multiple technologies or pivoting to a new manufacturing process isn’t always practical for many pharmaceutical companies, especially startups and smaller biotech. However, CDMOs have the agility to invest in numerous platforms, develop partnerships with various technology providers, and guide companies to the best fit for their drugs. CDMOs are the matchmakers of the pharmaceutical industry, bringing pharmaceutical and life science technology suppliers together to create mutually beneficial partnerships.
For example, at the Center for Breakthrough Medicines (CBM), we know that adherent process scalability is one of the biggest hurdles to manufacturing cell and gene therapies. Frequently, companies find that the methods that worked for preclinical research or even Phase I and II trials can’t produce the same quality or quantity of product needed for Phase III and commercial. They often must switch between platforms, requiring complex comparability studies and potentially creating costly delays.
Due to their customized nature, each therapeutic has precise manufacturing needs, depending on the process and the product. Some therapies can be scaled up in a matter of days, while others take months to grow the cells and develop the therapeutic. One-size-fits-all solutions don’t work well with these therapies, so this is where a CDMO, who has invested in multiple technologies and can offer the best solution for your product, can be helpful.
A CDMO should have a plan of action for scalability at the beginning of its partnership with a company that does not involve expensive platform changes or unproven technology. While presenting their plan for manufacturing, the CDMO should provide evidence that their large-scale methods work by sharing research and whitepapers that support their modalities. One-size-fits-all solution proposals are a red flag that the CDMO hasn’t thoroughly researched each therapy’s particular needs.
Unique Challenges Need Creative Solutions
Drug companies should also choose a CDMO that streamlines these processes as much as possible to get the drugs to market faster. However, many CDMOs outsource so many elements in the manufacturing process that they slow down production. It’s common to find that the components needed to create cell therapies are manufactured in different locations, even in separate countries.
For instance, if the plasmids are manufactured in one place, and the viral vector is manufactured in another, you must ship one to the other to create a drug substance for cell therapy. Then, they may have to be sent to another site for cell therapy DP manufacturing and another for testing. Segmenting the manufacturing process like this can result in extra costs and delays.
At CBM, we manufacture and test all the components at a single facility, which reduces costs. Our samples travel down corridors rather than between countries. Our team is careful to select the right technology for each therapeutic. For example, we’ve used Corning® CellSTACK® and Corning® HYPERStack® culture chambers for many of our early-phase projects because they can create reproducible, consistent cell cultures in high yields with little development, critical for fast to clinic approach. For later phases, where larger-scale manufacturing is required, we are developing novel adherent capabilities unique to cell therapy applications.
Case Study: Stem Cell Therapies
CBM is currently partnering with the experts at Corning Life Sciences to develop advanced induced pluripotent stem cell (iPSC) therapies using closed and automated techniques. The aim of this partnership is to explore innovative methods and procedures for producing iPSC therapies in a closed and automated manner, thereby enabling CBM to manufacture large quantities of cells in a closed system. This is a crucial step towards the development of readily available “off-the-shelf” iPSC therapies, which are notoriously difficult to manufacture and require complex technological solutions when scaled up from bench research to commercial manufacturing.
First, scientists use precise gene editing tools to create the iPSCs from existing cells. Secondly, the new stem cells are differentiated into the desired cells to target a specific disease or condition. On a small scale, this involves a series of manual processes that, when scaled up, become laborious and risky. Simply put, the more hands-on the process is, the more opportunities there are for human error. Our team looked for an automated solution to produce these therapies faster and more reliably.
To scale up these allogenic cell therapies without compromising their integrity, our experts turned to Corning Life Sciences for help, knowing their reputation for empirically proven results. We are currently exploring the upcoming Ascent® Fixed Bed Reactor (FBR) technology platform for this research. FBRs can produce cell therapies more rapidly and in much greater numbers than cell culture stacks, and the Ascent FBR system has higher, more consistent yields than other platforms, making it an excellent choice for this project. Ultimately, this will help us bring these lifesaving drugs to market faster and with a more significant ROI for our partners.
The Future of Advanced Therapeutics is Automation
Thousands of viral vectors are in the research stage, moving into clinical trials. The old, labor-intensive manufacturing process will not work to produce the number of drugs that the market demands. Drug companies need new solutions to this problem, and CDMOs help them overcome these challenges through knowledgeable and experienced technology partners.
At CBM, our team is working on automating these processes as much as possible to bring more lifesaving drugs to market faster with fewer costs. To that end, in addition to upstream process development, we’re optimizing full-scale purification techniques, establishing high-throughput analytical capabilities, and creating innovations in adherent cell expansion. CBM partners with cutting-edge technology providers like Corning Life Sciences to bridge the gap between the possibilities of these advanced therapeutics and the realities of bringing them to the market.
About the Authors
Tatiana Nanda, Ph.D., has over 12 years of experience in biotherapeutics across MAbs and cell and gene therapies and is currently the Head of Cell Therapy and Drug Product Development at CBM. In this role, Tatiana is responsible for the design and implementation of a diverse and client-focused Cell Therapy and Drug Product service portfolio and the establishment of internal manufacturing platforms. Prior to joining CBM, she was in Janssen, where she led the DP scientific strategy and execution of Oncology and Ocular compounds across multiple modalities, including autologous CAR-Ts and AAV gene therapies. Prior to this, Tatiana worked at GSK in Biopharmaceutical Product Sciences. Tatiana has a BS in Microbiology from the University of Tennessee, an MS in Economics from Moscow State University, and a Ph.D. in Biophysics & Lifesciences from UT/ORNL.
Nikhil Tyagi, Ph.D., has 10+ years of experience in tumor microenvironment, immuno-oncology, and cell therapies. He is currently the Director of Cell Therapy Process Development at CBM and spearheads the development of internal and external client-focused cell therapy programs and initiatives. Prior to joining CBM, he developed process platforms for both autologous and allogeneic cell therapies at various biotech companies. Nikhil holds a Ph.D. in Biochemistry, specializing in tumor-targeted drug delivery, and has extensive experience in the field of cancer biology and cell therapy.
About the Center for Breakthrough Medicines
The Center for Breakthrough Medicines (CBM) is a cell and gene therapy contract development and manufacturing organization (CDMO) uniquely positioned to enable pharma and biotech companies to develop, test, manufacture, and market life-saving therapies and treatments on a global scale. Ideally located in the heart of Philadelphia’s Cellicon Valley, CBM has assembled the most accomplished cell and gene therapy experts in the world, armed with cutting-edge and innovative technologies, to offer scalable, best-in-class pre-clinical through commercial manufacturing capabilities, including process development, plasmid DNA, vector manufacturing, cell banking, cell processing, and a full suite of complementary and standalone testing and analytical capabilities.
Purpose-built and patient-driven, CBM was designed from the ground up to be a more-effective CDMO, providing single-source, end-to-end solutions to deliver true partnership and unprecedented value to its customers through teamwork, transparency, and speed-to-market dedication.
Learn more at https://breakthroughmedicines.com/
About Corning Life Sciences
Corning Life Sciences is a global, leading manufacturer of products for growing cells, bioprocess manufacturing, liquid handling, benchtop equipment, and glass. Corning strives to improve efficiencies and develop solutions that enable researchers to harness the power of cells to create breakthrough innovations. Corning supports research for several application areas, including core cell culture, bioprocess, cancer research, primary and stem cells, drug screening, cell and gene therapy, disease modeling, lab automation, and more. Learn more at www.corning.com/lifesciences.