How many of the following seven considerations for handling ADCs are of interest to you?
As the ADC pipeline matures, payloads become more powerful, and linker technology becomes more sophisticated, the operational demands surrounding ADC manufacturing are rapidly increasing. At the same time, development schedules are compressing and expectations for safety, reproducibility, and regulatory compliance continue to rise.
What may work in monoclonal antibodies is increasingly inadequate in ADCs. Nowhere is this more evident than in fluid handling and cold chain management, where traditional methods are reaching their limits.
Here are seven considerations that increasingly define how ADCs are handled today. Not in theory, but in real-world manufacturing environments where safety, precision, and scalability need to work together.
1. Prioritize safety when handling cytotoxic ADCs
Unlike traditional biologics, ADCs introduce cytotoxic risks directly into routine liquid handling steps. Even brief exposure during transfer, draining, or filling can pose a serious hazard to operators.
Cytotoxicity has reshaped facility and process design. Closed handling architectures are becoming the baseline. EU GMP Annex 1 reinforces this change by explicitly promoting closed systems to reduce both contamination risks and personnel exposure.
Cold chain operations add even more risk. Frozen products place mechanical stress on disposable containers, increasing the risk of bag breakage. Secondary packaging of disposable bioprocess containers during frozen handling adds an important layer of protection for both product integrity and operator safety.
2. Light: The invisible threat to ADCs
Exposure to light is unavoidable in biomanufacturing. For example, USP <790> Regulatory standards, such as , also require defined lighting conditions for visual inspection. However, not all light exposure is harmless.
Many ADC payloads contain photosensitive functional groups that can degrade under ambient or UV light. The challenge is further compounded by the fact that antibodies, linkers, and payloads each react differently and degradation can begin without obvious visual cues.
With a limited number of single-use bags offering essential UV protection, manufacturers are increasingly relying on secondary containment. Secondary packaging such as disposable bags or RoSS® shells that completely enclose the assembly can help reduce unnecessary exposure during transportation and storage, while black film materials provide additional protection when photostability risks are high.
3. Fluid path is the beginning of patient safety
Patient safety is designed long before medicines reach the clinic. In ADC manufacturing, closed system devices directly impact how accurately and consistently materials are transferred and filled.
Small variations in shape, internal volume, or process can result in product loss, residual volume, or dose variation. All of these factors are becoming increasingly important to patient safety. Poor control over fill paths complicates validation efforts and comparisons between sites.
Recipe-driven closed filling strategies can help address these risks by providing reproducible performance and predictable hold-up volumes. Establishing well-defined fluidic pathways early in development creates a more reliable foundation for scale-up and supports patient safety when working with potent substances.
4. The weakest link in the ADC cold chain
Freezing and thawing are some of the most critical moments in an ADC’s lifecycle. Known challenges such as cryogenic concentration, aggregation, and pH changes are well documented, but for ADCs, the linker is often the most sensitive point of failure. Many linker chemistries are temperature and pH dependent. Therefore, uncontrolled freeze-thaw cycles can compromise binding integrity, even if the antibody itself appears unaffected.
This began the transition to controlled, recipe-based freezing and thawing methods that help maintain molecular structure. By actively managing cooling rates, phase transitions, and thaw profiles, manufacturers can reduce variability and more effectively preserve critical quality attributes during storage and transportation.
5. Every drop counts: Losses are no longer acceptable
The value density of modern ADCs continues to increase. Improving drug-to-antibody ratios (DARs), increasingly powerful payloads, and advanced linker technologies have dramatically increased the financial impact of even small losses.
At the same time, the industry is expanding beyond classic ADCs to next-generation bioconjugates, such as nanoparticle-based systems and polysaccharide-conjugated vaccines. In this environment, losses due to contamination, container breakage, excessive holdup, or inaccurate filling can no longer be tolerated.
Today, protecting the value of a product requires the same level of precision and control that has long been associated with manufacturing active pharmaceutical ingredients.
6. ADC manufacturing rarely follows a straight line
Batch sizes fluctuate, indications evolve, scaling requirements change, and production is often transferred between in-house sites and CDMOs.
Solid infrastructure struggles under this volatility. Manufacturers are increasingly seeking solutions that allow them to scale volumes without redesigning, change container formats without recertification, and efficiently transfer processes between sites.
Modular and flexible platforms combined with automation across filling, freezing, storage and transportation are emerging as key enablers of process flexibility. Scalable process solutions for single-use systems like bags and bottles help manufacturers adapt to change without compromising safety, control, and compliance.
7. Think end-to-end
Many ADC processing challenges cannot be solved alone. Operator safety, product quality, cold chain stability, and scalability are deeply interconnected.
An end-to-end handling strategy that combines sealed fluid management, protected storage, and controlled freezing and thawing can reduce interface and manual intervention. As a result, the process becomes more robust and easier to control. Plus, it’s easy to adapt as your ADC program evolves.
Handle ADCs with confidence without compromise
Single-use support helps manufacturers implement secure, closed, and scalable ADC fluid and cold chain management throughout development and commercial manufacturing steps. From automated filling and protected storage to controlled freezing and thawing, our integrated solutions are designed to navigate these seven (or more) key ADC workflows in fluid and cold chain management. Handling increasingly powerful and valuable ADCs with confidence helps reduce manufacturing risk while maintaining product integrity.
