A4BEE · CDMO

Nine Ways to Make a Drug

From small-molecule chemistry to CAR-T cell therapy — nine manufacturing modalities, what each demands of a CDMO, and the science and history behind them.

Łukasz Paciorkowski

Łukasz Paciorkowski

CEO, A4BEE

  • Field guide
  • 9 manufacturing modalities
  • CDMO
  • 9 min read
9
distinct manufacturing modalities in commercial use
28%
CAGR for cell & gene therapy — the fastest-growing modality
≤900 Da
molecular-weight ceiling to cross the blood-brain barrier
$3M+
per-patient price for some gene and CAR-T therapies

A tablet of ibuprofen and a single patient’s dose of CAR-T cells have almost nothing in common. Manufacturing complexity is set by modality, not disease.

Ask what a CDMO manufactures and the honest answer is: it depends which of nine fundamentally different technologies the drug is built on — different raw materials, different equipment, different containment, different quality systems. Here’s a field guide to the modalities that make up the biotech and pharma manufacturing landscape, and what each one demands.

01 By the numbers

Nine technologies, one industry

Nine distinct manufacturing technologies are in commercial use across biotech and pharma today — and the gap between the simplest and the most complex has never been wider.

9

modalities in commercial use

28%

CAGR for cell & gene therapy

The fastest-growing — and most complex.

≤900 Da

molecular-weight ceiling

To cross the blood-brain barrier as a small molecule.

$3M+

per-patient price

For some gene and CAR-T therapies.

02 Tier one

Built in a reactor, not grown in a cell

The oldest branch of the industry: molecules assembled through organic chemistry rather than living systems — stable, cheap at scale, and now the slowest-growing tier.

Small molecule / API

Best for: pain, infection, cardiovascular disease

A chemically synthesized compound, typically under 900 daltons — stable enough for a pill, small enough to cross the blood-brain barrier. The oldest and still the largest drug category by volume.

Peptides

Best for: diabetes & obesity (GLP-1s)

Short amino-acid chains built via solid-phase synthesis — a manufacturing middle ground between small-molecule chemistry and biologics. GLP-1 demand has caused a genuine capacity crunch.

Oral solid dose (OSD)

Best for: any chemically stable drug

Not a substance but a finished form: API blended, granulated, compressed and coated into tablets. Highest-volume, lowest-cost-per-dose format in the industry — and the slowest-growing.

  • 1963 → Nobel. Solid-phase peptide synthesis, invented by Bruce Merrifield at Rockefeller University, won the 1984 Nobel Prize in Chemistry — the same year hybridoma antibody technology won in Medicine.
  • 1843 tablet press. William Brockedon's patent — originally designed for pencil leads — made the modern compressed tablet practical. A single line now presses over a million tablets a day.
  • Nanogram-scale containment. HPAPI payloads (used in ADCs) need containment down to nanograms per cubic meter — some of the most extreme containment engineering in any industry.

03 Tier two

Biologics and engineered chemistry

Antibodies, proteins and hybrid molecules grown or engineered from living systems — higher complexity, higher growth, and the segment where most CDMO investment is now going.

A therapy that would travel straight to a disease target without harming the rest of the body.

Paul Ehrlich Physician-scientist, coined the concept of the 'Zauberkugel' (magic bullet), early 1900s

Monoclonal antibodies (mAbs)

Best for: cancer, autoimmune disease

A single, uniform antibody grown in engineered CHO cells inside 2,000–25,000-liter bioreactors, then purified through chromatography. The largest biologics category by revenue.

Biologics & biosimilars

Best for: diabetes, hemophilia, anemia

Any therapeutic protein made in a living system — bacteria, yeast or mammalian cells. Biosimilars must prove 'high similarity' to the original, not exact replication.

Antibody-drug conjugates (ADCs)

Best for: breast cancer, lymphomas, solid tumors

A monoclonal antibody chemically linked to a highly toxic payload — three manufacturing disciplines (biologics, HPAPI chemistry, conjugation) under one roof.

mRNA / lipid nanoparticle (LNP)

Best for: infectious-disease vaccines

Genetic instructions synthesized cell-free and wrapped in a protective lipid nanoparticle. Skips cell culture entirely — a facility can be built and validated far faster.

Sterile fill-finish

Best for: any drug entering the bloodstream directly

The final step: filling a bulk drug substance into vials, syringes or cartridges in cleanroom isolators. Became the real COVID bottleneck — vaccines could be made faster than filled.

  • Never patented. Hybridoma technology — behind every monoclonal antibody — won Köhler and Milstein the 1984 Nobel Prize. They never patented it, believing it should be free for science.
  • First recombinant DNA drug. Humulin (1982) put the human insulin gene into E. coli, turning bacteria into insulin factories — Genentech's Boyer and Swanson pioneered the technique.
  • Two decades to Nobel. Karikó and Weissman's mRNA breakthrough was dismissed for years before the 2023 Nobel Prize — and COVID-era demand made vial-filling capacity, not vaccine production, the real bottleneck.

04 Tier three

Personalized, per-patient manufacturing

Cell & gene therapy is the newest and most complex modality — and the only one where the 'batch' is a single patient's own cells.

CGT treats disease by replacing or correcting a faulty gene, or engineering a patient’s own cells to fight disease — most famously CAR-T, where a patient’s T-cells are reprogrammed to recognize and kill cancer. Because each dose is made from that one patient’s cells, it can’t be mass-produced or stockpiled.

  • One patient, one batch. Chain-of-custody tracking from apheresis to infusion matters as much as the biology.
  • Vector is the bottleneck. Producing viral vectors (AAV, lentivirus) at scale is one of the hardest problems in biomanufacturing — vector yields, not final cell processing, usually cap the whole industry.
  • 28% CAGR. The fastest-growing modality by a wide margin — and the most complex and expensive to manufacture.

05 The data

Growth is inverted

The modalities with the longest manufacturing history are, almost without exception, the ones growing slowest — and the newest, hardest-to-manufacture modality is growing fastest by a wide margin.

CAGR by modality

Oral solid dose: 3% 3% Oral solid dose Small molecule: 4% 4% Small molecule mAbs & biologics: 15% 15% mAbs & biologics Cell & gene therapy: 28% 28% Cell & gene therapy
CAGR by modality
LabelValue
Oral solid dose3%
Small molecule4%
mAbs & biologics15%
Cell & gene therapy28%
Complexity and growth move together. Source: A4BEE synthesis of public CDMO market reporting
  • Oral solid dose — ~3%. The slowest-growing modality, and the one with the longest manufacturing history.
  • Small molecule / API — ~4%. Mature, high-volume, low-cost-per-gram — still the largest segment, but growth has slowed to single digits.
  • mAbs & biologics — ~15%. Roughly twice the overall CDMO market's growth rate, driven by oncology and immunology pipelines.
  • Cell & gene therapy — ~28%. The fastest-growing modality by a wide margin — and the most complex and expensive to manufacture.

The remaining modalities — ADCs, mRNA/LNP, sterile fill-finish and peptides — are all growing at double-digit or “high” rates too, but their source reporting doesn’t converge on one precise figure the way these five do.

06 All nine

The full picture

Production method, typical scale unit, growth and complexity, side by side.

ModalityProduction methodTypical scale unitGrowth (CAGR)Complexity
Small molecule/APIChemical synthesiskg batches~3–5%Low–medium (high for HPAPI)
mAbMammalian cell culture (CHO)Bioreactor liters (2,000–25,000 L)~15%High
Biologics (broader)Microbial or mammalian cell cultureBioreactor liters~15%High
ADCmAb + HPAPI + conjugation chemistryGrams of payload, liters of mAbDouble-digitVery high
Cell & gene therapyViral vector + cell engineering, per-patientPer-patient batch / vector liters~28% (fastest)Highest
mRNA/LNPEnzymatic synthesis + nanoparticle formulationGrams of RNAHigh (post-COVID rebasing)Medium–high (new skill set)
Sterile fill-finishAseptic filling/lyophilizationUnits filled per hourMid–high (capacity-constrained)High (regulatory)
PeptidesSolid/liquid-phase synthesiskg of resin-bound chainHigh (GLP-1 driven)Medium–high
Oral solid doseGranulation, compression, coatingTablets/capsules per hour~2–4% (slowest)Low

07 So what

What this means for a CDMO

Modality isn't just a technical detail — it's the single biggest lever on what a manufacturing site needs to be capable of.

  • Process complexity. OSD and small molecules are one manufacturing discipline. ADCs and CGT combine two or three — biologics, chemistry, conjugation, viral vector production — often across different facilities.
  • Data intensity. A per-patient CAR-T batch needs chain-of-custody tracking from apheresis to infusion; a tablet press line needs high-throughput batch records. Both are compliance-critical, but the data shape is completely different.
  • Containment & quality. Nanogram-level HPAPI containment and sterile fill-finish isolators sit at one extreme; oral solid dose manufacturing, while still GMP-regulated, carries far lower single-batch risk.

That’s also why digital maturity varies so much across the CDMO landscape. The modalities racing ahead in growth — biologics, ADCs, cell & gene therapy — are exactly the ones where paper batch records and siloed data stop scaling first: too many process variables, too much per-batch documentation, too little tolerance for manual transcription error. We mapped how that plays out across fifty of Europe’s leading CDMOs in Europe’s €36bn CDMO market — and its digital divide. Modality tells you what a plant has to be good at manufacturing; digital maturity tells you whether it can prove it did.

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