The more than 1,300 active studies on cell and gene therapies in development on ClinicalTrials.gov demonstrate the appetite for innovative medicines that address unmet treatment needs. However, there are inherent barriers to advancing development in cell and gene therapies.

The talent market is tight, and massive investments are required to create a technological footprint to manufacture enough product to advance through the R&D stage with an eye toward expansion and commercialization. That’s why biopharmaceutical companies big and small are looking to contract development manufacturing organizations (CDMOs) that offer solutions to hasten development.

The maturation of the CDMO space

Already, around 90 percent¹ of biotech companies use CDMOs to manufacture their products, which may explain why the analytics firm Evaluate expects the CDMO market to outpace pharma growth through 2028.² In a recent webinar on the state of the industry, the firm said contract manufacturers are becoming increasingly important and adept partners for drugmakers working on complex treatments and drugs. They can also help companies secure funding when they are brought into the development stage early by signaling the ability to meet development milestones.³

Hence, companies that were traditionally considered vendors relegated to manufacturing roles are now the innovators, leveraging their technology, facilities, and expertise on behalf of partners and becoming technology leaders. The appeal of CDMOs as strategic business partners makes sense given the forecast value of outputs. The U.S. cell-therapy market was valued at around $2.9 billion in 2023 and is projected to reach $19.7 billion by 2033, a compound annual growth rate of 21.2% between 2024 and 2033.⁴

Part of being a technology leader is specialization, and it’s one trend we’re seeing among CDMOs.

Specialization is key, and M&A is supporting this trend

Given the range of cell-based therapies—from stem-cell therapies to viral-vector vaccines to gene-edited therapies—there is an immense need for specialization. Not every CDMO will have the expertise and technology to develop every hypothesized therapy and bring it through to commercialization, although they can bring value when they “undertak[e] commissioned projections and offer…unique solutions.”⁵

However, achieving specialization poses a big challenge. Thus, some companies are turning to mergers and acquisitions (M&A) to solve this problem. Nearly 250 M&A transactions involving CDMOs were announced publicly between 2017 and 2021.⁶

Examples of notable M&A transactions involving CDMOs have included ThermoFisher Scientific’s agreement to pay $1.7B for Bammer to expand its specialized viral vector gene-therapy services.⁷ Similarly, in 2019, Cognate BioServices acquired Cobra Biologics, which has expertise in plasmid DNA, viral vector, and protein,⁸ only to then be bought by Charles River Laboratories. Charles River increased its footprint further by adding Vigene Biosciences, which specializes in CGMP viral-vector manufacturing, used for gene therapies and gene-modified cell therapies.^9,10

The growing demand for specialized CDMO services has also led to a virtual explosion in new companies in the space, including List Labs, Pluri CDMO, SK pharmteco, and National Resilience.

Solving cell expansion

Given their complexity and the fragile nature of cells, the technology required to develop therapies requires investment in and deep understanding of the technology that incorporates quality control measures, specialized manufacturing facilities, and cGMP manufacturing standards. Hence, CDMOs with expertise in cell expansion are poised to help their partners more quickly bring innovations to market by offering their services and facilities from the drug-candidate concept stage, through research and development, and later through commercialization.

For example, Pluri has over 20 years of experience developing the technology and human capital experienced with expanding cells efficiently and with batch-to-batch consistency. The company offers technological support throughout the CDMO value chain, from isolation and selection of cells, to expanding and harvesting them, through storage and shipment, and all the way through administration of the therapies over time.

Pluri’s proprietary cell-expansion technology is based on a packed-bed scaffold system that doesn’t leave the cells exposed to the massive shear forces used inside other kinds of stirred-tank bioreactors that impact scalability and cell quality. Instead, the scaffold system mimics the natural environment in which the cells grow and supports expansion of cells into 3D tissues, which preserves their inherent biology. This technology allows Pluri to work across autologous and allogeneic products, primarily using human stem cells, including mesenchymal (MSC) and pluripotent (iPSC) cells, immune cells, gene-edited cells, and exosomes preparation.

Other companies such as Charles River also offer cell-expansion services, but with a different focus. For example, they offer vector-viral packaging, molecular cloning, gene synthesis, shRNA, and CRISPER/CasP cloning.¹¹ Fujifilm Diosynth Biotechnologies is another company investing in cell-expansion services, among others worldwide.¹²

Therefore, in selecting a CDMO partner, all expertise is not relevant, and choosing focused experts who understand and prioritize your product is vital. It’s also important to ask questions about workflow processes to ensure that everyone agrees on standards for quality, safety, data-gathering, and suppliers.

Off-the-shelf allogeneic treatments

The majority of today’s approved-for-use cell-based therapies are genetically modified using autologous cells donated from a patient’s own body for personal use. While they are effective, there are barriers to their use. For example, with CAR-T therapy for certain blood cancers, some of the challenges lie in the logistic challenges to create the therapy locally, related therapy toxicities, and their expense.^13,14

Hence, there is a shift in demand to create allogeneic off-the-shelf therapies created from a healthy donor to use across patient populations. Allogeneic therapies would—by design—be manufactured in significantly greater quantities and have a reduced cost associated with increased supply.

Yet, to make the leap from individual therapy to mass-produced therapy, innovators need to overcome more than just the ability to create cells in massive quantities. Rather, CDMOs venturing into allogeneic therapy need to develop solutions that take the entire upstream and downstream production process into account.

One example of a specialized CDMO for allogeneic products is PluriCDMO, which is biotechnology company Pluri’s recently announced independent business division. Pluri developed a quality solution to support the production of allogeneic products (the Plurimatrix system) through automatic reactor harvesting systems, concentration and washing processes suitable for tens of billions of cells, automatic final formulation processes for large quantities of drug product and fill-&-finish systems that support the filling, visual inspection and labeling of hundreds of vials.

What’s next

Treating cancer and other difficult-to-treat conditions through cell-based therapies is clearly an all-hands-on-deck situation, but the required investments in innovation and related research and development will require partners specialized to accommodate a variety of hypothesized treatment approaches.

One way to advance R&D is to expand specialized training and educational programs at our world’s top-tier universities to build out the skilled workforce needed to develop cell therapies. Biotech companies also need trained personnel with real-life experience, which can only be gotten on the job. Of course, starting at the university level with specialized coursework and internships will develop the skills needed over time.

On the other hand, CDMOs are increasingly taking the lead in developing next-generation cell therapies, working with partners eager to advance research in lieu of developing their own infrastructures and specialized workforce. Selecting the right CDMO comes down to creating a checklist of qualities that ensure a collaborative work environment.

Companies need to consider a CDMO’s expertise across cell types and regulatory environments, its size and capacity, and the quality and oversight associated with the physical facilities and workflows. Partnering with a CDMO is a long-term relationship, so careful consideration and vetting ensure that both sides are contributing to future results. 
It’s certainly worth the investment to select a CDMO carefully. The forecasted growth rate for cell and gene therapies explains this trend, with one estimate suggesting cell and gene therapies could see a compound annual growth rate of 46% through 2028, valued at $86 billion in global sales by that year.¹⁵ 

References

1. Langer, Eric. Cell and Gene Therapy Bioprocessing: Hiring and Capacity Crunch on the Horizon. Cell & Gene. May 21, 2020. Accessed July 31, 2024. https://www.cellandgene.com/doc/cell-and-gene-therapy-bioprocessing-hiring-and-capacity-crunch-on-the-horizon-0001
2. Kansteiner, Fraiser. 2024 Forecast: As CDMOs Come Off Pandemic’s Highs and Lows, Employment and Funding Hitches Persist. Fierce Pharma. January 8, 2024. Accessed July 31, 2024. https://www.fiercepharma.com/pharma/2024-forecast-cdmos-business-booming-even-employment-and-funding-hitches-persist
3. Evaluate. How Can CDMOs Succeed in 2024 and Beyond? Evaluate. Accessed July 31, 2024. https://www.evaluate.com/webinar/how-can-cdmos-succeed-2024-beyond/
4. BioSpace. Cell Therapy Market Size to Grow at 22.67% CAGR Till 2033. BioSpace. April 22, 2024. Accessed July 31, 2024. https://www.biospace.com/cell-therapy-market-size-to-grow-at-22-67-percent-cagr-till-2033#:~:text=The%20U.S.%20cell%20therapy%20market,21.18%20%25%20from%202024%20to%202033
5. Kamal, Nabilah. The Fourth Revolutionary Wave of Biologics Manufacturing: CDMOs Empower Large-Scale Production of Biologics. Frost & Sullivan. Accessed July 31, 2024. https://www.frost.com/uncategorized/the-fourth-revolutionary-wave-of-biologics-manufacturing-cdmos-empower-large-scale-production-of-biologics/
6. Heiber, Isabelle. CDMOs Are Leading Innovation for Pharmaceutical Partners. EY. July 14, 2022. Accessed July 31, 2024. https://www.ey.com/en_us/insights/strategy/how-cdmo-companies-are-leading-innovation-for-pharmaceutical-partners
7. Thermo Scientific to Acquire Brammer Bio, a Leader in Viral Vector Manufacturing. 2019. Available at: https://ir.thermofisher.com/investors/news-events/news/news-details/2019/Thermo-Fisher-Scientific-to-Acquire-Brammer-Bio-a-Leader-in-Viral-Vector-Manufacturing-2019-3-24/default.aspx. Accessed July 31, 2024.
8. Cognate BioServices Announces Acquisition of Cobra Biologics. 2019. Available at: https://www.prnewswire.com/news-releases/cognate-bioservices-announces-acquisition-of-cobra-biologics-300951144.html. Accessed July 31, 2024.
9. Charles River. Charles River Completes the Acquisition of Cognate BioServices. Criver.com. March 29, 2021. Accessed July 31, 2024. https://www.criver.com/insights/charles-river-completes-acquisition-cognate-bioservices
10. Charles River Laboratories Completes Acquisition of Vigene Biosciences. 2021. Available at: https://ir.criver.com/news-releases/news-release-details/charles-river-laboratories-completes-acquisition-vigene. Accessed July 31, 2024.
11. Charles River. Cell and Gene Therapy CDMO Solutions. Criver.com. Accessed July 31, 2024. https://www.criver.com/products-services/cell-and-gene-therapy-cdmo-solutions
12. Fujifilm to Invest Additional $1.2 Billion to Expand its Large-Scale Cell Culture CDMO Business in North Carolina. 2024. Available at: https://fujifilmdiosynth.com/about/news/fujifilm-to-invest-additional-1-2-billion-to-expand-its-large-scale-cell-culture-cdmo-business-in-north-carolina/. Accessed July 31, 2024.
13. Cliff ERS, Kelkar AH, Russler-Germain DA, Tessema FA, Raymakers AJN, Feldman WB, Kesselheim AS. High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions. Am Soc Clin Oncol Educ Book. 2023 Jun;43:e397912. doi: 10.1200/EDBK_397912. PMID: 37433102.
14. Gajra A, Zalenski A, Sannareddy A, Jeune-Smith Y, Kapinos K, Kansagra A. Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice. Pharmaceut Med. 2022 Jun;36(3):163-171. doi: 10.1007/s40290-022-00428-w. Epub 2022 Jun 7. PMID: 35672571; PMCID: PMC9217916.
15. Lohr, Adam. 2023’s Market Outlook for Cell and Gene Therapies. Cell & Gene. February 14, 2023. Accessed July 31, 2024. https://www.cellandgene.com/doc/s-market-outlook-for-cell-and-gene-therapies-0001#:~:text=There%20are%20over%201%2C500%20ongoing,therapies%20registered%20with%20ClinicalTrials.gov

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Lior Raviv joined Pluri in 2011 and currently serves as Chief Technology Officer. Prior to that, Mr. Raviv served as VP Operations & Development, Process Development Engineer, Projects Manager and Product development Team leader at Pluri. Prior to joining Pluri and during the years 2010-2011, Mr. Raviv held the position of R&D Analytical Researcher at Teva Pharmaceutical Industries. Mr. Raviv holds a M.Med.Sec in pharmacology from the Ben Gurion University and a B.S.c, in Biotechnology engineering from the Ben Gurion University.