# Payload-linker synthesis (high-potency API)

Source: https://onco.cc/technologies/high-potency-payload-synthesis/  
OnCo record `high-potency-payload-synthesis` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Payload-linker synthesis makes the cytotoxic small molecules inside ADCs (exatecan, MMAE, DM1, PBD dimers), whose occupational exposure limits sit in the nanogram range, in facilities built so a speck of dust cannot harm a worker. A handful of licensed sites such as Lonza and WuXi STA supply them, and their lead times gate hundreds of ADCs in development.

## Summary

Camptothecin derivatives (exatecan, DXd), auristatins (MMAE/MMAF), maytansinoids (DM1/DM4), and PBD dimers are synthesised under OEB 5/6 containment by specialists (Lonza, MilliporeSigma, WuXi STA, Piramal, Sterling, Ajinomoto Bio-Pharma, Levena, Cerbios, Kelun in-house) and sold as ready-to-conjugate linker-payloads. Supply is a gating factor for the hundreds of ADCs in development.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-08
- Tags: supporting
- Principle: Multi-step synthesis and purification of cytotoxic small molecules and linkers under engineered containment, with occupational exposure limits in the nanogram range.
- Strengths: Standardised, reusable linker-payload building blocks
- Limitations: Few licensed sites; Long lead times; IP encumbrance on best payloads

## Sources

- 21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211

## Connected records

- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/), [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [ADC bioconjugation manufacturing (CDMOs)](https://onco.cc/technologies/adc-cdmo-manufacturing/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Small-molecule API synthesis](https://onco.cc/technologies/small-molecule-api-synthesis/), [The ADC supply chain (antibody, payload-linker, conjugation, fill)](https://onco.cc/technologies/adc-supply-chain/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- companies: [Lonza](https://onco.cc/companies/lonza/), [Piramal Pharma Solutions](https://onco.cc/companies/piramal-pharma-solutions/), [Sterling Pharma Solutions](https://onco.cc/companies/sterling-pharma-solutions/), [WuXi XDC](https://onco.cc/companies/wuxi-xdc/)

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