Antibody-drug conjugates have moved from a promising concept to one of the most actively developed drug classes in oncology. Behind that progress lies a manufacturing challenge that is becoming more demanding by the year.
The global ADC market was valued at around $14.75 billion in 2024 and is projected to reach approximately $36 billion by 2034, driven by an expanding clinical pipeline and growing confidence in ADCs as a precision oncology tool.
"ADC development has matured considerably, but that maturity has come with greater complexity," says Brett Verstak, Director of Cell Line Development at Abzena.
"Developers are working with more sophisticated antibody formats, novel linker chemistries, and highly potent payloads that demand specialised containment and process understanding from the outset."
With the experts at Abzena, the leading bioconjugates and biologics CDMO and CRO, we examine why bioconjugation expertise has become central to ADC success, and what developers need to consider when selecting the right manufacturing partner for next-generation programmes.
The three-component challenge
An ADC consists of three interdependent elements: the antibody, the linker, and the cytotoxic payload. Each must be developed, optimised, and scaled individually before they can be brought together through bioconjugation. Disruption to any one component has the potential to compromise the entire construct.
The linker is particularly critical, directly influencing pharmacokinetics, safety, efficacy, and manufacturing robustness. An optimal linker must exhibit high plasma stability to prevent premature payload release, while enabling efficient payload liberation at the target site through predictable and reproducible mechanisms. As developers push towards more sophisticated cleavable linker designs, the bioconjugation process itself becomes more demanding to control at scale.
The payload side of the equation presents its own challenges because most ADC payloads are classified as highly potent active pharmaceutical ingredients (HPAPIs), requiring dedicated containment infrastructure that relatively few organisations have in place. Handling a high-potency API requires specialised high-containment facility infrastructure, and the multi-step bioconjugation process demands stringent cGMP manufacturing oversight.
Why outsourcing has become the norm
Given the breadth of capability required, it is perhaps unsurprising that in-house ADC development has become the exception rather than the rule. An estimated 70 to 80 percent of ADCs currently under development are outsourced, a figure that reflects how difficult it is for any single organisation to command the full range of expertise needed across antibody engineering, linker synthesis, payload handling, and bioconjugation, whether this is for R&D or for GMP manufacturing activities.
For emerging biotech companies in particular, the barriers to building that manufacturing capability internally are significant. Access to GMP-compliant containment facilities, qualified analytical teams, and process development experience all take years and considerable capital investment to establish. Partnering with an experienced CDMO from early-stage development allows those teams to move candidates forward without those delays.
The quality of that partnership matters more than many developers initially anticipate. "Choosing a CDMO is not simply a question of who has available capacity," says Verstak. "You need a partner who understands your molecule, can troubleshoot across the full construct, and has the regulatory experience to support you through the clinic and into commercial manufacture. That combination is rarer than it might appear."
The complexity of next-generation ADC design
By 2025, there were more than 200 clinical-stage ADC programmes across all phases, with many advancing beyond traditional targets like HER2 or Trop-2 and beyond traditional payloads like MMAE or DXd into novel territories. That pipeline diversification is driving demand for bioconjugation expertise that can flex across different antibody formats, including bispecifics, as well as more varied payload classes.
Site-specific conjugation, which attaches the payload to a defined position on the antibody rather than a random site, is increasingly favoured for its ability to produce more homogeneous constructs with better characterised drug-to-antibody ratios. This approach, whilst offering real therapeutic advantages, places additional demands on the bioconjugation process and requires close integration between the antibody development and conjugation teams.
An integrated development model, where antibody production, linker-payload chemistry, conjugation, and formulation are handled within a coordinated programme rather than in sequence, is proving central to reducing cycle times and avoiding costly late-stage process changes.
Building towards commercial scale
The journey from preclinical ADC candidate to commercial product involves significant process evolution, and early decisions have a long reach. Conjugation conditions, purification strategies, and analytical methods established in Phase I can be difficult to revisit once a programme advances, making it important to select approaches that are manufacturable at scale from the outset.
"We work with developers who sometimes arrive with a construct that performs well in the lab but has not been designed with scalability in mind," says Verstak. "The earlier those conversations happen, the better. Bioconjugation is not a step you can treat as an afterthought once the antibody is ready."
For sponsors advancing ADC programmes in an increasingly competitive landscape, the message is clear-cut. The science of ADCs has advanced substantially, and the development and manufacturing infrastructure supporting it must keep pace. Experienced CDMO partners, capable of integrating biological and chemical expertise across the full construct, are not simply a convenience. They have become a prerequisite for getting these therapies to the patients who need them.
Sources
https://www.technavio.com/report/antibody-drug-conjugates-market-industry-analysis
https://www.bioprocessintl.com/therapeutic-class/cdmo-selection-the-last-barrier-to-adc-advancement
