The Pharma Letter: Why ADC development needs a new level of bioconjugation expertise

Antibody-drug conjugates (ADCs) 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, adding: “Developers are working with more sophisticated antibody formats, novel linker chemistries, and highly potent payloads that demand specialized containment and process understanding from the outset.”

With the experts at Abenza, a leading bioconjugates and biologics CDMO and CRO, examining why bioconjugation expertise has become central to ADC success, and what developers need to consider when selecting the right manufacturing partner for next-generation programs.

The three-component challenge

An ADC consists of three interdependent elements: the antibody, the linker, and the cytotoxic payload. Each must be developed, optimized, 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 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 organizations have in place. Handling a high-potency API requires specialized 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% of ADCs currently under development are outsourced, a figure that reflects how difficult it is for any single organization 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 Mr 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,” he noted.

Building towards commercial scale

The journey from pre-clinical 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 program 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 Mr Verstak, adding: 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 programs 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.

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