Why Managing Potency and Degradation are Crucial in ADC Cleaning Validation

Paul Lopolito, director of Technical Services at STERIS, outlines key challenges in cleaning validation for antibody-drug conjugates (ADCs) in an interview with BioPharm International® during INTERPHEX 2026, occurring in New York City on April 21–23. Lopolito participated in the panel discussion, “Cleaning Considerations for Antibody Drug Conjugate (ADC) Products.”

Lopolito highlights the need for risk-based strategies tailored to complex drug modalities, emphasizing how ADCs introduce new considerations compared with traditional small- or large-molecule products.

ADCs combine highly potent small-molecule drug substances with large-molecule biologics, creating distinct validation challenges. According to Lopolito, differences in degradation profiles, health-based exposure limits, and analytical methods mean that a single cleaning validation approach cannot be universally applied across ADC products. These challenges are further compounded in multi-product facilities, in which multiple ADCs may be manufactured using shared equipment.

He also notes that some ADC manufacturing processes rely on solvents incompatible with single-use systems, necessitating reusable equipment and robust cleaning validation protocols. This increases the importance of contamination control and accurate analytical verification.

How does degradation impact ADC cleaning validation strategies?

A central issue in ADC cleaning validation is managing the degradation behavior of both molecular components. Large-molecule biologics are often intentionally degraded during cleaning processes using pH, temperature, or alkalinity to reduce their therapeutic activity. In contrast, small-molecule payloads require careful handling to avoid degradation into potentially more toxic byproducts, Lopolito explains.

“Understanding a degradation profile is an important element in cleaning validation,” he says.

This dual-modality consideration requires a nuanced, risk-based approach that integrates knowledge of degradation pathways, analytical method performance, and acceptable exposure limits. Lopolito emphasizes that the convergence of established strategies for small and large molecules presents both a challenge and an opportunity for the industry.

He adds that advancing ADC cleaning validation will depend on aligning these approaches to ensure safe, reliable manufacturing outcomes across increasingly complex therapeutic pipelines.

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About the speaker

Paul Lopolito, Director, Technical Services, STERIS

Lopolito has more than two decades of industry experience in bio/pharmaceutical manufacturing and laboratory research, specializing in process cleaning, cleaning validation, and contamination control. At STERIS Life Sciences, he provides global technical support through field consultations, training, and analytical testing and manages the PACE program.