Technical Articles

Market

The newcomers: emerging biotechs now own two-thirds of the pipeline

Emerging biopharma's share of the global R&D pipeline has doubled in 20 years – from 33% in 2002 to 51% in 2017, 63% in 2021 and 67% in 2022, against 23% for large pharma.¹ Small teams now carry most of the pipeline, yet few have a senior CMC lead in-house.

Development risk

Slipping approvals: 1 in 15, down from 1 in 10

The likelihood of approval from Phase I has fallen from 10.4% (2014 report) to 9.6% (2016), 7.9% (2021) and 6.7% (2024).² For 2011–2020, phase transition success rates were 52.0% (Phase I→II), 28.9% (II→III), 57.8% (III→filing) and 90.6% (filing→approval); biologics reached approval from Phase I at 9.1% against 5.7% for small molecules.³

CMC is the one risk a sponsor controls – yet it is often reviewed only after a setback.

Regulatory

Manufacturing problems now outrank efficacy in FDA rejections

In an analysis of complete response letters for 43 novel drugs later approved (2020–2024), deficiencies cited were: manufacturing facilities 65%, CMC (process & product) 51%, labelling 44%, efficacy 26%, safety 26% and PK/PD 14%.⁴

CMC packages and facilities are rarely stress-tested before filing.

Cell line development

Complex molecular formats are harder to make

To the end of 2025 the FDA had approved 113 standard IgG mAbs, 27 other formats, 15 bispecifics and 14 ADCs.⁷ Standard mAbs still make up two-thirds of approvals and 69% of biologics revenue (2024), while bispecific approvals rose five-fold, from 3 by 2021 to 15 by 2025.^8,9 Each format brings its own development problem – chain mispairing and aggregation for bispecifics, three arms to assemble for trispecifics, inclusion bodies and aggregation for fragments, and lower expression for fusion proteins.^10,11,12

Complex formats need a host, vector and screen chosen for the molecule, not a reused mAb platform. More on cell line development.

Cell line development

Race to file: speed can leave the clone unproven

Using a non-clonal pool can cut CMC work before first-in-human from around 15 months to 3 months – an 80% reduction.¹³ But the FDA expects high assurance of single-cell origin, does not recommend pools for Phase 1, and moving to a clone later needs a full comparability study.^14,15 Short stability studies also miss late productivity drift: 8–63% of CHO lines prove unstable.¹⁶

Scale-up

Lack of scalability: where transfer delays happen

A biologic passes through three or four transfers in its life, and most delays occur when a 10 mL–10 L development process moves to 50–200 L pilot scale.^17,18 Each month of delay can cost $80M for a biologic selling $1B a year; one missed gap in equipment, raw materials or an analytical method can delay launch by 6–12 months; and rerunning a failed 2,000-litre batch costs $100K+.^17,19

Few programmes compare sending and receiving sites, or build a scale-down model, before GMP.

Laboratories & compliance

GMO regulations: what UK labs must do before first use

The GMO (Contained Use) Regulations 2014 set out a sequence: assess the risk to human health and the environment; classify the work (Class 1–4), which sets the containment measures; obtain GM safety committee advice for Class 2 and above; notify HSE and have the premises acknowledged before first use; then operate – Class 2 work notified, Class 3 and 4 requiring HSE consent.²⁰ If this is skipped or done late, work cannot legally start until HSE acknowledges the premises, and HSE inspectors can enter premises and demand records.²⁰

With fitted lab vacancy at 1% across the Oxford–Cambridge–London cluster in 2024 and prime Cambridge lab rents up 69% between 2018 and 2024 (from about £42.30 to £71.50 per sq ft, with quoting rents at £77 by Q2 2026), the containment class and GM risk assessment often come after the lease is signed and the lab is laid out – and containment added after fit-out means rework.^21,22,23 In England, offices can now switch to lab use without planning permission, although building works may still need it.²⁴

Technology transfer

Where and how an asset is made is now part of its value

The pharmaceutical CDMO market reached $174B in 2025, with the top five holding 30%: Lonza alone more than 12%, the other four of the top five 18% between them, and all other CDMOs 70%.²⁵ A House bill naming WuXi passed in September 2024 but was not enacted; the US BIOSECURE Act was then signed into law in the FY2026 NDAA in December 2025; WuXi AppTec was added to the Pentagon's 1260H list in June 2026 (enforcement halted by a court in August 2026), and OMB is due to publish its list of biotech companies of concern by 18 December 2026.²⁶

Supply-chain restrictions lead buyers to ask whether a process can move – and the answer needs CMC review. Few deal teams can judge whether a process can move sites.