While in vivo CAR-T therapies eliminate complex ex vivo manufacturing, they introduce a new critical variable: the patient's own immune system. The therapy's efficacy relies on modifying T-cells within the body, but each patient's immune status is different, especially after prior treatments. This makes optimizing and standardizing the dose a significant challenge compared to engineered cell therapies.

Unlike traditional drug development, cell therapy logistics require extremely close, integrated relationships with contract research (CRO) and manufacturing (CDMO) organizations. Due to the direct line from patient to manufacturing and back, these partners function as critical extensions of the core team to ensure timeliness and safety.

Unlike small-molecule drugs, biologics manufacturing cannot be simply scaled up on demand because "the process is the product." A superior manufacturing and supply chain capability is not a back-office function but a key market differentiator that commercial teams must leverage to win customers and outpace competitors.

Rather than waiting for late-stage development, biotech startups should integrate commercial planning into early trials. This means building in data collection for payers, pricing, and patient access from the start. This "think with the end in mind" approach ensures the company has the right data for pivotal trials and market access.

The focus in advanced therapies has shifted dramatically. While earlier years were about proving clinical and technological efficacy, the current risk-averse funding climate has forced the sector to prioritize commercial viability, scalability, and the industrialization of manufacturing processes to ensure long-term sustainability.

Despite promising data, Sana's CEO provides a sober timeline for their type 1 diabetes cell therapy. While clinical proof-of-concept ("does it work?") is expected within 12-18 months, even a "super optimistic" commercial launch would not happen until later this decade. This highlights the lengthy process of scaling manufacturing and navigating regulatory pathways.

Unlike most biotechs that start with researchers, CRISPR prioritized hiring manufacturing and process development experts early. This 'backwards' approach was crucial for solving the challenge of scaling cell editing from lab to GMP, which they identified as a primary risk.

Unlike autologous therapies where one batch treats one patient, a single batch of an allogeneic therapy can treat thousands. This scalability advantage creates a higher regulatory bar. Authorities demand exceptional robustness in the manufacturing process to ensure consistency and safety across a vast patient population, making the quality control challenge fundamentally different and more rigorous.

To overcome production bottlenecks, Legend Biotech employs a diversified manufacturing strategy. They operate their own large facilities in the US and Belgium while also contracting with pharmaceutical giant Novartis to produce their CAR T therapy. This enables a rapid scale-up to a planned 10,000 annual doses.