Beyond CHO: New Protein‑Manufacturing Platforms Poised to Transform Complex Biologics in 5–10 Years

Major advances in molecular design — especially within the antibody field — are outpacing manufacturing capabilities. Although Chinese hamster ovary (CHO) cells have been the industry workhorse since the 1970s, their limitations are becoming increasingly clear as companies push toward more structurally complex proteins and larger native human proteins.

Why CHO remains dominant — and where it falls short

CHO cell lines enabled industrial production of many recombinant proteins because they support complex post‑translational modifications and deliver high yields for standard antibodies and smaller proteins. However, CHO systems can be sensitive to temporal and pH fluctuations, struggle with complex bonds (for example, disulfide bridges), and are difficult to manipulate genetically. These challenges make scale‑up costly and can force developers to abandon promising programmes — particularly for bispecific antibodies, large enzymes, and antibody‑cytokine fusion proteins.

Interview highlights: Björn Cochlovius on manufacturing innovation

Björn Cochlovius (BC): "Molecular innovation is moving fast, but manufacturing hasn't kept pace. To deliver complex biologics at scale, we must accept and pursue manufacturing innovation. The major players will likely accelerate only as the operational pain of current methods becomes harder to bear."

BC notes that big pharma and large CDMOs are often cautious about adopting new, unproven technologies; this conservatism slows industry uptake and prolongs dependency on CHO. He adds that CDMOs focused on large molecules do not always prioritize inventing solutions to CHO‑specific problems, creating an innovation bottleneck.

Emerging alternatives: specialised platforms, not a single replacement

Rather than one platform replacing CHO, Cochlovius expects several specialised expression systems to mature, each tailored to particular molecule types. Eleva Biologics, for example, used a moss‑based expression system to produce recombinant Factor H — a protein the industry had struggled to generate for more than a decade — enabling the progression of CPV‑104 into early‑stage clinical trials.

BC: "I don't think we'll see CHO disappear soon — billions have been invested in CHO facilities. But alternative systems should grow in importance where they solve specific manufacturing problems."

Where alternatives could make the biggest impact

Two areas stand out: (1) production of large, native human proteins such as certain enzymes, where CHO has historically been problematic, and (2) antibody derivatives — including bispecifics and antibody‑cytokine conjugates — which are often hard to scale with CHO systems. Suitable alternative platforms could rescue programmes that otherwise would be dropped for manufacturability reasons.

Adoption timeline and early commercialization

Cochlovius estimates it may take roughly five to ten years for alternative methods to be widely embraced. Eleva has begun licensing its CHO alternative to CDMOs (3PBIOVAN was an early partner), reflecting an incremental path to broader industry uptake: partners test technologies, demonstrate fit for specific molecule types, and then scale adoption across the sector.

Bottom line: The coming decade is likely to see a more diverse manufacturing ecosystem for biologics. CHO will remain critical for many products, but specialised platforms — chosen for particular molecules — should expand industry capacity to bring complex, precision medicines to patients at scale.