Cell and gene therapies (CGTs) are among the world’s most expensive therapies to develop, manufacture, and administer. In fact, the average cost of bringing a CGT to market has increased to $1.94 billion. However, the market is expected to grow significantly in the coming years, creating abundant opportunities at every level of the development cycle and supply chain.

CGTs are the frontier of precision medicine, providing therapies that are highly specific and targeted to the particular disease or pathology. So far, we’ve seen CGTs revolutionize patient care for sickle cell disease, spinal muscular atrophy, certain cancers like leukemia and lymphoma, inherited retinal disease, and more.

While many hoped that CGTs would provide cures, they are more often long-term therapies that replace dysfunctioning cells or genes to temporarily treat diseases. While CGTs aren’t necessarily cures, they are a game changer in precision therapeutics.

But what does this mean for manufacturers? Are CGTs worth the investment, and how can manufacturers mitigate risk in order to capitalize on the many opportunities in the CGT pipeline?

Commercial Success of Cell & Gene Therapy

In the last 10-15 years, CGT has transitioned from academic experiments to commercially viable products. With CGT emerging as a commercially viable way to treat human disease, we are seeing an increase in interest and a more commercially focused approach for manufacturing, approvals, and quality system processes. Because of this rapid growth, skilled professionals with expertise in CGT — specifically large-scale production — have become more readily available, reducing previous challenges in hiring teams with the right expertise.

While still in its early stages, the FDA and other regulators have more case studies and standards to guide CGT development, helping manufacturers meet industry expectations in cleanliness, cellular assays, purification, and risk management. In fact, in 2019 the FDA predicted that they would be approving 10 to 20 cell and gene therapy products per year by 2025.

As the industry matures, drug companies are better at understanding how to design and produce cell and gene products. However, because of the unique nature of cells and genes, there will always be unique twists and turns to each therapeutic. While you can standardize processes, CGT will always require a tailored approach.

Opportunities of Cell & Gene Therapy for Manufacturers

When it comes to cell and gene therapies, the opportunities are abundant, especially for manufacturers.

CGT is a Rapidly Growing Field

The CGT industry is expanding rapidly, creating numerous opportunities. A rich pipeline of projects, especially from small biotech firms, presents potential for commercial success. There are currently more than 4,000 gene, cell, and RNA therapies in development, with an 11% year-over-year increase specifically in Phase I programs.

Innovation from Small Biotech

Many small biotech companies are taking bold, innovative steps, spinning off academic projects, and becoming more comfortable with commercialization. A significant majority, around 90%, of cell and gene therapies are currently in early development stages (Phase 1 and 2 clinical trials), indicating that a large portion of the field is still in the early development phase. While the majority of these will not make it to commercialization, the data reflects that there is no shortage of innovation in cell and gene development.

Robust Pipeline and Deal Flow

The deal flow between small biotech firms and large pharmaceutical companies is thriving, giving drug companies a variety of options to expand their portfolios. More than ​​4,000 therapies are in development, ranging from preclinical through pre-registration. Oncology and rare diseases are the top focus areas of gene therapy development in the pipeline, with the top five targeted diseases being:

• Myeloma
• Acute myelogenous leukemia
• Non-Hodgkin’s lymphoma
• B-cell lymphoma
• Ovarian cancer

Opportunities for CDMOs to Fill Specialized Gaps

Contract development and manufacturing organizations (CDMOs) that specialize in CGT can capitalize on the growing demand for specialized services. By becoming experts in specific therapeutic areas, CDMOs can position themselves as go-to partners for small biotech companies breaking into CGT for the first time. Advancing pipelines for these small biotech companies can even help specialized CDMOs who are highly experienced have the opportunity to build relationships with larger pharmaceutical companies, post-acquisition commercialization.

Risks of Cell & Gene Therapy for Manufacturers

There’s no doubt that cell and gene therapy offers abundant opportunities for manufacturers, but that doesn’t mean it’s necessarily a safe bet. There are also significant risks to consider before diving into a CGT project, from cost and scalability to quality control challenges.

High Cost

Cell and gene projects are expensive — the average cost of bringing a CGT to market has increased to $1.94 billion. This kind of investment requires awareness of budget constraints, shifting timelines, and ongoing challenges associated with manufacturing living systems.

Complex Manufacturing

There are so many unknowns when putting a living cell or genetic material into another body. Knowing where to insert it, when to activate it, and if the body will recognize it becomes a herculean effort to accomplish successfully. This creates an extremely complex manufacturing supply chain to ensure quality and efficacy of each therapy.

Lack of Standardization

While regulatory guidance is improving, the lack of industry-wide standardization still presents hurdles in clinical trials and scaling up production. It can be challenging to interface with regulators around cell and gene products, and there is no playbook for how to develop and manufacture a commercially successful therapy. Without the right expertise, manufacturers can waste time and money on costly mistakes or trial and error.

Scalability

By nature, cell and gene therapy is not a large-scale manufacturing process because it is very customized. Scaling up from a primary culture to large-scale production is complex, requiring careful selection of high-performing cells and robust reproducibility in manufacturing processes.

Quality Control Issues

In cell therapy, manufacturing living cells comes with a high risk of contamination and other failures. Fragile cells need to be cultured in highly controlled environments to avoid death or dysfunction. Gene therapy manufacturing is more straightforward due to advances in synthetic biology, but it still requires precision in drug design, gene sequencing, and the use of viral vectors for delivery.

Mitigate Risk and Seize CGT Opportunities with Pharmatech

While cell and gene therapies present opportunities for manufacturers, it’s important to understand and mitigate the inherent risks. Here are a few ways in which you can set yourself up for success with your next CGT project.

• Ensure that your understanding of the target product quality profile for your CGT product is translated to the critical quality attributes, and critical material attributes, and that justification for their controls are described in your CMC packages submitted to the FDA. Where there is no sufficient information to justify, make sure a risk assessment is conducted and risk mitigation measures are put in place.
• Establish trust with partners, conduct thorough due diligence of third parties such as CDMOs. Understand who you’re working with and their technical capacity to meet the unique needs of CGT manufacturings. Request clear demonstrations of their capabilities. We suggest a “show me, don’t tell me” approach.
• Understand your responsibility as the product development sponsor in ensuring quality and compliance, even if you are using third parties to execute.
• Understand the potential risks of limitations in your early stage programs to late stage clinical manufacturing, and product launch.
• For CDMOs, it’s crucial to invest in the right areas and avoid shortcuts that could lead to quality or safety issues.
• Ensure that your quality system is suitable for CGT and not a generic “borrowed” system from other industry sectors.

At Pharmatech Associates, we don’t approach anything with a cookie cutter solution. We work with you to understand what your expertise is, identify knowledge gaps, and create a tailored solution to match the unique needs of your project. Learn more about how Pharmatech Associates can help you navigate the complexities of CGT.