What are “3 Key Trends” shaping the CDMO industry in 2023 and beyond? ReciBioPharm’s chief scientific officer, Kai Lipinski, shares his thoughts with Contract Pharma.

Cell and gene therapies
The cell and gene therapy (C>) space has expanded rapidly since the first gene therapy gained approval in 1990. Technological advancements and a broader understanding of molecular engineering have led to a significant number of gene therapies entering the market. From therapies targeting mono-genetic diseases to blood-associated cancer types, the gene therapy space is clearly beyond the proof-of-concept phase. The subsequent success of gene therapies is reflected in the global gene therapy market, valued at over $7 billion in 2022. Between 2023 to 2030, this is expected to quickly expand at a compound annual growth rate (CAGR) of 19.1%.

As demand for personalized medicines and access to gene therapies grows, the biopharma industry can anticipate rising pressure to improve the manufacturability of these products to produce them at scale cost-efficiently. Single-use technologies, improved media supplements enabling high productivity, improved virus genome engineering, transfection & transduction enhancer molecules, targeted delivery and gene expression, new chromatography modalities, and suspension culture-based upstream options have been widely adopted by developers to improve the manufacturability of their products in recent years.

However, the current situation necessitates further improvements in manufacturing capabilities. In the future, we could see these advances manifesting in the form of continuous processing technologies or perfusion-based high-cell density culture, or other innovative manufacturing approaches. Other gene therapy viral vector systems might be developed to market maturity in the future, one example could be non-replicating HSV-1.

Analytical technologies
Manufacturing capabilities are not the only area where contract development and manufacturing organizations (CDMOs) can expect to see advancement in the next few years. Demand for new, revolutionary gene therapies has also driven improvements in analytical technologies.

The complexity of gene therapy products like viral vectors and the fact that they are manufactured in cellular host substrates has meant analytical characterization can be a significant challenge, requiring cutting-edge analytical capabilities. The analytical demands of regulatory bodies have become increasingly stringent as the gene therapy space has matured. Demonstrating the safety, potency, and efficacy of gene therapies to progress to clinical investigation is therefore becoming a greater challenge.

As a result, it’s now increasingly common for CDMOs to offer analytical developments comprised of sophisticated techniques such as digital PCR, flow virometry, virus mass photometry, Nano-Tracking-Analysis (NTA), Analytical Ultra-Centrifugation (AUC), SEC-MALS, or multi-angle dynamic light scattering, to name a few. But the current situation also indicates that still further improvements are required. In the years to come, advancements can be expected to focus on areas such as improving real-time process and product analytical technologies, analysis of vector integrity & toxicity, and gaining insight into side effects and lack/loss of stable efficacy.

Regulatory landscape for cell and gene therapies
In a rapidly changing and advancing C> landscape, we can expect the need for CDMOs to offer flexibility and agility in development and manufacturing to be an increasingly important factor for those in biopharma when selecting a partner.

Moving beyond 2023, new insights into why we see side effects and lack/loss of stable efficacy will continue to influence regulatory guidelines. CDMOs must be aware of guideline changes, and if possible, predict the changes to come. To respond quickly to a rapidly evolving regulatory landscape and the rising demands for gene therapies, CDMOs will need to continue to adopt new technologies and adapt to meet specific clients’ needs. Also, regulatory guidance and consultation, and CMC critical document support offered by CDMOs is highly appreciated particularly by early-phase biotech companies.

However, it will not be enough to offer flexibility, clients will also be seeking partners that can bring the cost of goods down. The high production costs associated with gene therapies are clearly demonstrated by the first gene therapy for a recently approved hemophilia B gene therapy (AAV5-hFIX-Padua). This one-time treatment costs $3.5 million, making it the most expensive drug in the world. CDMOs will need to consider implementing innovative manufacturing techniques and strategies to improve affordability and help broaden patient access to these critical medicines.