The Future of ADC Manufacturing

The production of ADCs is a complex process that involves several meticulous steps, such as conjugating monoclonal antibodies with cytotoxic agents and linkers. This process requires exceptional precision and control, especially when the Occupational Exposure Limits (OELs) for these substances fall below 30 ng/m³. The stability of ADCs is critically dependent on both the antibody and the linker-toxin components, each presenting its own unique challenges. Integrating these components into a final product adds an additional layer of complexity.

If the linker-toxin is unstable, the ADC may degrade, releasing toxic substances prematurely, which can diminish therapeutic efficacy and pose significant safety concerns for patients. To mitigate this risk, ADCs can be lyophilized (freeze-dried) from early stages of development. Cytotoxins, being highly potent and complex, require careful handling and production within high-containment facilities. Given their potency, only minute quantities are needed, which necessitates specialized techniques that are often impractical for large-scale drug manufacturing.

Production typically involves multiple steps that may be distributed across various manufacturing facilities. Each stage—ranging from antibody production and linker-toxin synthesis to their conjugation and final drug formulation—might be handled by different companies. This adds complexity and requires meticulous coordination and specialized testing to confirm that the ADC is safe, effective, and manufactured consistently. 1

As the ADC market continues to grow—with over 300 ADC candidates in development globally—new applications will play an increasingly vital role in enhancing patient outcomes for years to come. However, this progress must be approached with caution. The industry is rapidly evolving, adopting more efficient and safer production methods to protect both operators and the environment from exposure. Among these advancements, the integration of single-use isolators stands out as a transformative innovation.

The need for robust containment systems has never been more critical. Traditional rigid isolators, while effective, pose several challenges, including time-consuming cleaning processes, high capital costs, and the risk of cross-contamination between production batches.  Single-use or flexible isolators, also known as containment systems, have emerged as a highly viable alternative to traditional rigid isolators in ADC manufacturing. These systems offer several key benefits that address the unique challenges of ADC production.

ILC Dover conducted a cost analysis comparing cumulative expenses for a CDMO using single-use versus rigid isolators for multi-product ADC cytotoxic operations. Single-use isolators require a minor initial investment, with costs mainly linked to the number of products handled annually, including minimal maintenance and training expenses.

Rigid isolators, however, demand significant upfront capital. With ongoing multi-product projects, costly validated cleaning processes are required to meet regulatory standards and prevent cross-contamination, leading to higher cumulative costs over time. These costs, including residual toxin assays, QC tests, and downtime for cleaning, increase with the number of products handled.

The high cytotoxicity of ADC payloads also requires ultra-low cleaning limits, potentially adding further costs. Additionally, single-use isolators offer greater flexibility and ease of adaptation for capacity expansion compared to rigid isolators.

ILC Dover addresses the unique challenges of ADC production with customized, single-use solutions. The SoloADC™ Disposable Containment System provides unmatched containment, flexibility, and cost-efficiency. Whether managing multiple production stages across different facilities or adapting to evolving demands, SoloADC™ offers the versatility and high-performance containment required.

We offer comprehensive support from concept to delivery, working closely with pharmaceutical companies to ensure systems and components align perfectly with ADC workflow requirements. Our services include validation, integration, and training, enabling companies to focus on their core competencies while enhancing safety, efficiency, and consistency in ADC production.

Don’t let the complexities of ADC manufacturing hold you back.  Contact us today to learn how SoloADC™ can be tailored to your needs and take your ADC manufacturing to the next level. We offer a 5-day turnaround on custom drawings to bring your vision to life.

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