# Continuous-flow synthesis of ultra-potent ADC payloads to ease the capacity squeeze

Source: https://onco.cc/ideas/idea-reg-hpapi-continuous-flow/  
OnCo record `idea-reg-hpapi-continuous-flow` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The poisons carried by antibody-drug conjugates are so toxic that only a few factories can make them, and they are booked years ahead. Making them in small continuous reactors would ease the bottleneck.

## Summary

Capacity to make the toxins carried by ADCs, such as exatecan derivatives, maytansinoids and auristatins, is concentrated in a small number of contract manufacturers with multi-year lead times, and handling these toxins in batches, even in milligram quantities, requires costly containment. Continuous-flow chemistry in enclosed micro- or meso-reactors reduces the inventory of toxic intermediates at any moment, shrinks containment footprint and allows numbering-up rather than scale-up. The proposal is a pre-competitive programme to develop and regulator-qualify flow routes for the three most used payload classes and license them openly to manufacturers.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Qualified flow routes cut the cost of goods of payload-linker per gram by at least a third and reduce contract lead times for new ADC programmes from over 18 months to under nine.
- Rationale: Continuous manufacturing is already accepted by FDA and EMA for several small molecules and is well suited to hazardous chemistry; the payload chemistries are known and the constraint is capital and containment, both of which flow reduces.
- Proposed test: Fund two academic-industrial groups to demonstrate GMP-grade flow synthesis of exatecan and MMAE at 100-gram scale, with regulator engagement on the control strategy, and publish cost and lead-time comparisons.
- Maturity: preclinical-evidence
- Actor: engineering

## Sources

- Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018): https://doi.org/10.1001/jamaoncol.2018.0977

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [Payload (ADC)](https://onco.cc/terms/payload/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- key papers: [Total Costs of Chimeric Antigen Receptor T-Cell Immunotherapy](https://onco.cc/key-papers/paper-hernandez-jama-oncol/)

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