What Can ADC Producers Learn from HPAPI Manufacturing?

Antibody-drug conjugates (ADCs) are a novel type of therapeutic compound used in precision medicine, particularly oncology. They couple monoclonal antibodies with anticancer drugs via specialised linkers, promising:

• Targeted delivery: ADCs deliver their cytotoxic (anti-cancer) payload directly to cancerous cells, minimising off-target effects typical of traditional cancer therapies.

• Reduced toxicity: The monoclonal antibody component of an ADC ensures the drug component is delivered exclusively to the target antigen (i.e. a specific molecule found on the surface of cancer cells).

Compared with conventional systemic anti-cancer therapies (SACT) like chemotherapy, ADC-based treatment promises to reduce damage to non-diseased cells and increase the effectiveness of treatment. However, this therapeutic sophistication introduces new levels of manufacturing complexity – complexities that those familiar with high-potency active pharmaceutical ingredient (HPAPI) production may find strikingly familiar.

ADC manufacturing is not an entirely new approach, but rather an intensification of the challenges already present in workflows. For producers entering or scaling-up ADC production, revisiting best practices from the HPAPI domain offers a practical and technically grounded advantage.

HPAPI production requires robust containment strategies. These compounds are defined by their low occupational exposure limits (OELs), typically under 1 µg/m^3, and some as low as 10 ng/m^3. ADC payloads – often derived from ultra-potent chemotherapy agents like auristatins or maytansinoids – frequently fall into even more hazardous categories, with OELs dropping below 1 ng/m^3.

This escalation in potency demands physical containment but also airtight procedural integrity. Lessons learned from HPAPI isolator designs that are directly transferable to ADC facilities include:

• Pressure cascade management – prevents cross-contamination by maintaining controlled air pressure differentials between adjacent rooms, meaning hazardous particles are isolated within production environments.

• Integrated isolator-dryer units – combine drying equipment with isolation technology to guarantee safe processing conditions.

• Closed transfer systems that have been optimised for HPAPIs – can be readily adapted to manage ADC intermediates, particularly during conjugation and purification phases.

What differentiates ADCs is the biological component. While the small molecule payload requires high-containment handling, the antibody requires low-bioburden conditions. Bridging these two requirements necessitates hybrid processing environments where containment philosophy must meet bioprocess engineering. Companies with experience in both HPAPI containment and sterile manufacturing technologies are uniquely equipped to support this evolution.

HPAPI manufacturing demands precision powder handling and technologies that minimise loss, ensure dose consistency, and eliminate cross-contamination. In ADC workflows, these capabilities are mission-critical, but why?

• Payload quantities – ADC batches can be so small that even microgram losses are economically and therapeutically significant.

• The conjugation step – where the cytotoxic drug is chemically bound to the antibody, demands an exacting stoichiometry.

• The drug-antibody ratio (DAR) – must fall within a narrow target range to ensure both efficacy and safety.

• HPAPI weighing systems – equipped with gravimetric dosing and real-time monitoring, offer the resolution and containment required for this level of precision.

Moreover, this is not a single-point challenge. From early payload processing through conjugation and formulation, maintaining consistent handling conditions prevents degradation, contamination, and batch variability. Modular, closed-system equipment developed for HPAPI operations can often be retrofitted with sterile barriers or operated in cleanroom environments, bridging the gap without complete process re-engineering

Flexibility has become a core design principle in HPAPI production, especially in facilities serving CDMOs or companies with evolving pipelines. ADC developers can benefit immensely from this philosophy. With many ADC programmes starting at the clinical stage, the ability to scale processes without redesigning infrastructure is a competitive advantage.

What has emerged from HPAPI operations is a blueprint for modular and adaptable facilities:

• Compact footprints
• Mobile containment units
• Plug-and-play process equipment

These concepts map well to ADC facilities, where production runs can vary in scale and scope, and where new molecular entities are frequently added to pipelines.

The integration of multipurpose containment zones – capable of supporting both small-scale R&D and commercial batch sizes—allows ADC manufacturers to maintain compliance while accelerating timelines. These types of environment are where experience in containment engineering, environmental monitoring integration, and cleanroom-compatible system design converge.

From a regulatory standpoint, the overlap between HPAPI and ADC production is substantial. Both must meet stringent GMP standards, implement rigorous cleaning validation protocols, and demonstrate robust containment performance. Where they diverge is in the layering of biologic handling protocols on top of already complex chemical workflows.

Risk-based approaches to containment validation, established through decades of HPAPI experience, can inform ADC risk assessments. Using tools like surrogate testing, containment performance evaluations (CPEs), and occupational hygiene data, manufacturers can confidently map out safe operational envelopes for ADC production.

Vendors that have supported HPAPI clients through these regulatory landscapes bring valuable foresight to ADC projects, particularly in identifying critical control points, implementing scalable containment solutions, and providing data-driven validation documentation.

By leveraging cross-disciplinary expertise, especially from solution providers who have supported both HPAPI and ADC projects, manufacturers can reduce risk, enhance throughput, and maintain compliance in an increasingly complex therapeutic landscape.
The future of oncology treatments lies in potency with precision. And for ADC producers, the path to mastering this balance may begin with the lessons learned in HPAPI manufacturing.