Partnering for ADCs: What to look for in a contract development and manufacturing organisation (CDMO)

As antibody drug conjugates, or ADCs, play an increasingly pivotal role in targeted therapies, the choice of a contract development and manufacturing organisation (CDMO) partner can make or break an ADC development programme. ADCs, which combine a monoclonal antibody with a cytotoxic drug to ensure selectivity and potency, are among the most complex therapeutic modalities available today. Due to the critical components involved, ADC development requires precision at every step—from linker-payload synthesis to conjugation, formulation, and preclinical and ADC clinical manufacturing. 

With stringent requirements for containment, analytical method development, precise conjugation, and regulatory compliance, the success of an ADC programme hinges on the capabilities of a partner with extensive expertise across every part of the process. In this article, we’ll take a closer look at the importance of choosing the right ADC CDMO, discuss key capabilities to look for in a partner, and talk more about how we support ADC development and clinical manufacturing at Sterling.

Effective ADC projects require a delicate balance of safety, efficacy, and speed, and the margin for error at any stage of the process is razor-thin. A CDMO not only requires the ADC experience, analytical equipment and technical knowledge to support the delivery of ADCs, it also requires the specialised containment, and knowledge and expertise with different linkers, payloads, monoclonal antibodies, and conjugation chemistries that high-quality ADC development and manufacturing demands.  

The right ADC CDMO brings more than just facilities and instrumentation though. Crucially, they bring partnership and foresight. The right ADC CDMO will anticipate challenges before they become an issue, working in true scientific partnership with the customer to find solutions; harnessing proven processes to streamline development and manufacturing, and simplifying the approval process by leveraging strong regulatory relationships, extensive analytical expertise and a communication style tailored to their customer.  With so much riding on success and an increasingly competitive landscape, an ADC-specialised CDMO is more than just a nice-to-have, it’s a requirement for long-term project success.

Partnering with a CDMO that provides ADC-specific expertise means gaining access to a broad set of capabilities that address the unique demands of these complex therapeutics. Below are six critical competencies to prioritise in your search for an ADC partner.

ADC development requires the seamless integration of multiple disciplines, from small molecule development to conjugation expertise, containment and hazard evaluation, analytical method applications, and seamless clinical-stage manufacturing. A CDMO that delivers on all of these capabilities can support stronger project continuity to reduce risk, simplify tech transfer, and support faster progression from preclinical to clinical development. 

Conjugation is a defining step of ADC development, as well as one of the most technically demanding. The right partner will provide:

• Expertise in both stochastic and site-specific conjugation techniques to optimise drug-to-antibody ratios (DAR)
• Familiarity with working with a range of different linkers both cleavable and non-cleavable
• Experience working with a range of different payload classes, such as topoisomerase inhibitors, DNA damaging agents, tubulin inhibitors and degraders
• Proven methods for optimising conjugation efficiency

By offering expertise in each of these areas, a qualified partner can aid in developing tailored ADCs that meet the customer’s specific expectations.

ADC analytical services are one of the most critical pillars of successful ADC development, as they require thorough analysis at every stage to ensure purity, safety, efficacy, and compliance. An ADC-specialised CDMO should offer a full suite of analytical services to handle the structural complexity of ADCs, including: 

• Drug-to-antibody ratio analysis using techniques like UV-VIS spectroscopy, hydrophobic interaction chromatography (HIC), and LC-MS for DAR profiling and batch consistency
• Mass spectrometry expertise to analyse pH stress, oxidative stress, and other elements of stability
• Forced degradation studies to understand degradation pathways and inform formulation decisions

These just scratch the surface of analytical competencies required for successful ADC development. When evaluating an ADC CDMO, consider the breadth of their analytical services, expertise in tailoring analytical methods for a specific ADC, and ability to adapt methods as a project evolves.

Due to the potent toxins involved in ADC development, expertise in specialised handling and containment are non-negotiable. A partner with the experience and infrastructure to support high-potency API (HPAPI) development can apply their containment expertise to safely and effectively handle cytotoxins. Beyond infrastructure that supports occupational exposure limits (OEL) < 1 μg/m³, an outsourced partner’s specialised team should have thorough training on safe handling procedures, cleaning, and cross-contamination prevention.

An ADC CDMO’s approach to quality and compliance should not be reactive, they must be an integral part of development and clinical ADC manufacturing. Look for a partner that operates under strict cGMP conditions, has comprehensive quality control procedures in place, and demonstrates a proven track record of successful regulatory submissions for ADCs.

The complex timelines and multiple moving parts involved in ADC development and manufacturing necessitate not only scientific expertise but also a strong and thorough project management approach. When searching for an ADC CDMO, prioritise those that offer dedicated project managers to serve as a key point of contact and are known for their close collaboration and partnership. Strong internal and customer collaboration ensures that issues are identified and rectified early, timelines stay on track, and all teams involved in the project remain tightly aligned.

Now that we’ve summarised key things to look for in an outsourced partner for ADC development and manufacturing, let’s see how this translates to the CDMO selection process. Below are several important questions to ask when evaluating a CDMO for your ADC programme. 

• What stages of the ADC development lifecycle do you support? Can I work with you for clinical ADC manufacturing? 
• What analytical techniques do you use to characterise ADCs throughout development?  
• What conjugation chemistries can you support, and how do you optimise drug-to-antibody (DAR) ratio? 
• What types of payloads have you worked with? 
• What containment measures do you have in place? What level of containment do your facilities support? 
• Can you describe your project management structure? How will we work together? 
• How do you support regulatory filings for ADCs, and what experience do you have with global regulatory agencies? 

These questions are designed to help you evaluate not only what an ADC CDMO can offer but how they deliver on their offerings. Make sure that your potential partner responds to these questions with transparency, provides detailed examples, and demonstrates a genuine commitment to ongoing collaboration. 

While the right capabilities are critical in an ADC CDMO, at Sterling, we know that the right ADC development and clinical manufacturing partner delivers more. Our integrated approach combines the expertise of our global facilities to support ADC programmes from early development through to clinical ADC manufacturing. With purpose-built containment facilities, comprehensive analytical services, and a track record of success in ADC development and clinical manufacturing, we are well-suited to help our customers efficiently and effectively develop complex therapeutics.

Even more invaluable is the collaborative partnership we offer our customers at every step of the way. We work as an extension of our customers’ teams, treat their products as our own, and maintain close collaboration and transparency. That’s why we’re more than a typical ADC CDMO—we’re a PDMO, or partnership development and manufacturing organisation. 

If you’re interested in finding out more about our ADC development and clinical manufacturing services, speak to an ADC expert.