ISPE 2026年会演讲：ADC清洁验证中降解评估、分析方法选择与验证风险降低

At the 2026 ISPE Annual Meeting & Expo, taking place 18-21 October in Washington, D.C., USA, Brian Bosso, Manager of Technical Services, STERIS, will explore these questions during his session, "Degradation During Cleaning of ADCs." Through real-world laboratory case studies, attendees will gain practical insights into cleaning validation for mAbs, HPAPIs, and ADCs, including approaches to evaluating degradation and inactivation, selecting analytical methods, supporting technology transfer, and bridging laboratory studies with full-scale manufacturing operations.

1. Cleaning is often viewed as a downstream activity, yet it can have significant implications for project success. What are the 2-3 most common cleaning-related challenges or pitfalls that companies encounter when working with mAbs, HPAPIs, and ADCs, and why are these issues becoming increasingly important for the industry?

One of the biggest challenges I see is that cleaning is often treated as something to figure out after the manufacturing process has already been established. By that point, teams may realize that the product is more difficult to remove, degrade, or detect than expected. That can create significant challenges during validation and technology transfer.

Another common issue is selecting cleaning agents without generating enough laboratory development data to support the decision. Regulatory expectations continue to emphasize the need for cleaning process development and cleanability studies to demonstrate that a cleaning agent is effective and appropriate for its intended use.

For ADCs and other highly potent compounds, understanding degradation is equally important. It's not enough to know that a residue was removed. We also need to understand what happens to that molecule during cleaning, whether it degrades, whether it becomes inactive, and whether those degradants present any additional risk. That assessment is important not only from a product quality and regulatory perspective, but also for protecting the end patient receiving the medication and the operators who may be exposed to residues during manufacturing and cleaning activities. As more companies work with increasingly potent and complex therapeutics, these questions are becoming more important than ever.

2. ADCs present unique challenges due to their potency and degradation characteristics. What are some of the most interesting or surprising findings from the laboratory case studies you'll be sharing, and what makes them especially relevant for today's facilities?

One of the more interesting findings from our studies was how quickly some ADC-related activity could be eliminated under appropriate cleaning conditions. In fact, enzyme inactivation occurred faster than measurable degradation of the monoclonal antibody component and combined ADC. The implication is that biological inactivation may occur before complete molecular degradation. Residual, intact protein that remains on the surface would be biologically inactive, reducing the potential hazard of the residue. From a cleaning validation perspective, that reinforces the importance of evaluating not only residue removal, but also degradation and inactivation mechanisms.

We also observed that both mAbs and ADCs demonstrated good cleanability under practical cleaning conditions. In the case presented, a 1% formulated alkaline detergent at elevated temperature achieved effective cleaning in short contact times.

Another takeaway was the value of using multiple analytical techniques. Methods such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), ultra-high-performance liquid chromatography (UHPLC), and enzymatic activity assays each provided a different perspective on what was happening to the residue during cleaning. Looking at degradation and inactivation together provided a much more complete understanding than relying on a single test method.

3. How will this session help attendees make better decisions around cleaning-agent selection, cleaning validation strategies, analytical testing, and technology transfer, ultimately reducing risk, avoiding costly delays, and supporting regulatory expectations?

My goal is to provide attendees with a practical framework they can apply to their own products and facilities. The session walks through real laboratory studies and discusses how those results can be used to support cleaning-agent selection, establish cleaning parameters, and justify validation strategies.

We'll also discuss how to select analytical methods based on the question you're trying to answer. During development, methods such as high-performance liquid chromatography (HPLC), SDS-PAGE, or enzyme activity assays can provide detailed information on degradation and inactivation. For routine monitoring, approaches like visual inspection and total organic carbon (TOC) may be more practical, though carryover limits must be considered.

Ultimately, the objective is to help companies make more informed decisions earlier in the process. Better process understanding can reduce validation risk, support smoother technology transfers, and help avoid the costly delays that can occur when cleaning considerations are left until the end of a project.

4. Your presentation discusses techniques such as visual inspection, TOC, HPLC, and enzymatic activity assays. How can attendees apply these approaches to bridge laboratory studies with full-scale manufacturing operations and improve confidence in their cleaning validation programs?

One of the key themes of the presentation is understanding the role each analytical method plays throughout the cleaning validation lifecycle. Not every method needs to be used routinely, but every method can contribute valuable information during development.

For example, HPLC, SDS-PAGE, and enzymatic activity assays can help characterize degradation and inactivation mechanisms during laboratory studies. Those studies help establish which cleaning parameters are most effective and whether degradation is occurring under the selected conditions.

Once that process understanding is established, facilities can transition to more practical monitoring methods such as visual inspection and TOC for day-to-day verification. The result is a stronger scientific connection between laboratory data, cleaning validation activities, and routine manufacturing operations.

5. For professionals involved in facility design, startup, commissioning, manufacturing, validation, quality, or regulatory compliance, what is the one key lesson or takeaway they can expect to gain from this session that makes it a must-attend at the 2026 ISPE Annual Meeting & Expo?

If I had to narrow it down to one takeaway, it would be that effective cleaning validation starts with understanding the product and what happens to that product during cleaning. Too often the focus is solely on residue removal, but for biologics, HPAPIs, and ADCs, degradation and inactivation can be equally important considerations.

Attendees will leave with a better understanding of how to evaluate cleaning performance, select analytical methods that provide meaningful information, and generate laboratory data that can be applied to validation and manufacturing. Whether you're involved in facility design, startup, commissioning, manufacturing, quality, validation, or regulatory compliance, that process understanding can significantly reduce risk and improve outcomes across the cleaning validation lifecycle.

Learn How to Strengthen ADC Cleaning Validation Through Better Process Understanding

As biologics, HPAPIs, and ADCs become increasingly complex, manufacturers face growing pressure to develop scientifically sound cleaning strategies that support product quality, operator safety, technology transfer, and regulatory compliance. Understanding how residues degrade or become inactivated during cleaning, and selecting analytical methods that provide meaningful data throughout the cleaning validation lifecycle, can help organizations reduce risk and make more informed decisions earlier in development.

Learn more and register today for the 2026 ISPE Annual Meeting & Expo.