Modalities
Antibody Drug Conjugates
Antibody drug conjugates (ADC) represent a breakthrough in targeted cancer therapy, combining the precision of monoclonal antibodies with the potency of cytotoxic drugs. By delivering powerful treatments directly to cancer cells, ADCs provide an alternative solution that enhances efficacy and minimizes side effects.
What are Antibody Drug Conjugates?
Antibody drug conjugates (ADCs) consist of three essential components. The process begins with a monoclonal antibody (mAb) that specifically recognizes and binds to antigens on the surface of tumor cells. Unlike traditional therapies, which adversely impact all cells, the use of mAbs allows for the cytotoxic payload to only target cells that express a specific antigen that may affect all cells. This targeted approach ensures that the cytotoxic payload is delivered primarily to cells expressing the target antigen.
The payload, a highly potent drug, is designed to induce apoptosis in the targeted cancer cell upon delivery. Often 100 to 1000 times more cytotoxic than conventional chemotherapies, these payloads are uniquely suitable for targeted applications. Given their extreme potency, payloads also present significant safety risks to operators during ADC development and manufacturing.
The final component is a chemical linker that connects the antibody to the payload. The linker is vital as it must keep the payload stable during circulation and specifically release it only inside the target cell. Premature payload release can increase off target effects, potentially harming healthy cells and reducing therapeutic efficacy by lowering the effective dose delivered to the tumor. This may also contribute to the development of tumor resistance over time, complicating treatment.
Challenges and Solutions in Antibody Drug Conjugate Manufacturing
Antibody Drug Conjugate (ADC) manufacturing is a complex, multi-step process involving conjugation, filtration, purification and formulation of monoclonal antibodies, cytotoxic payloads, and chemical linkers.
Key challenges include
- Managing potency of the payloads
- Minimizing cytotoxin exposure to operators
- Ensuring consistent drug-to-antibody ratios (DAR) across batches
- Containment and storage
From early-stage development to commercial production, Repligen offers integrated solutions across key unit operations, including antibody production, conjugation, drug-linker preparation, closed system connectivity, and ADC formulation. These solutions enable optimization of ADC production processes for improved yields, product quality, operator safety and cost-effectiveness.
KrosFlo® RS TFF System
Scalable, Closed-System TFF for Antibody Drug Conjugate Concentration and Formulation
The KrosFlo RS tangential flow filtration system is engineered for the demanding ultrafiltration and diafiltration steps central to ADC downstream processing. Its fully closed, single-use flow path design minimizes operator exposure to cytotoxic compounds, a critical requirement when handling highly potent ADC payloads.
With automated pressure and flow control, the KrosFlo RS delivers reproducible concentration and buffer exchange performance from development through clinical-scale production, supporting consistent drug-to-antibody ratio (DAR) and product quality across batches.
TangenX® Flat Sheet Cassettes
Validated Performance in Antibody Drug Conjugate Solvent Environments
In ADC manufacturing, ultrafiltration and diafiltration (UF/DF) steps must maintain high product recovery while operating in the presence of challenging solvents used during conjugation and purification.
TangenX® SIUS™ Gamma and TangenX® SC cassettes from Repligen are specifically designed to deliver reliable UF/DF performance in these demanding environments. Built with chemically robust membranes, these single-use TFF cassettes demonstrate excellent membrane stability in the presence of common ADC solvents such as dimethyl sulfoxide (DMSO) and dimethylacetamide (DMAC), helping manufacturers maintain consistent flux, product yield, and process robustness during ADC concentration and buffer exchange.
Their closed, sterile fluid path supports safe operation in hazardous ADC processes by minimizing operator exposure to potent payloads and solvents while simplifying implementation in GMP manufacturing environments.
Together, these capabilities make TangenX SIUS Gamma and TangenX SC cassettes a powerful solution for ADC UF/DF processing, enabling scalable, solvent-compatible, and safety-focused filtration workflows for next-generation bioconjugate therapies.
Spectrum® Hollow Fiber Filters
Versatile Filtration for Antibody Drug Conjugate Research and Early-Stage Development
Spectrum hollow fiber filters offer a broad range of membrane materials, molecular weight cutoffs, and surface chemistries suited to the early-phase development and small-scale processing of antibody drug conjugates.
Their compact format and low hold-up volume make them well adapted for precious sample recovery during initial ADC characterization and feasibility studies.
Spectrum hollow fiber filters provide the flexibility researchers need to screen and optimize filtration conditions before advancing to larger-scale TFF cassette-based processes.
PATsmart™ Analytical Solutions
Smarter Process Insight from Antibody Production Through ADC Formulation
ADC manufacturing requires confidence at every step, from upstream antibody production through conjugation, purification, concentration, and final formulation. PATsmart™ process analytics technologies from Repligen help biomanufacturers generate timely, actionable process insight to support consistent product quality, improved process understanding, and more efficient decision-making across ADC workflows.
For upstream antibody production, PATsmart technologies such as REBEL® XT, MAVEN®, and MAVERICK® help teams monitor and optimize key process parameters, including media composition, nutrient consumption, metabolite trends, and bioreactor performance. These insights can support more consistent mAb production before the antibody enters the ADC conjugation workflow.
For downstream ADC development and manufacturing, SoloVPE® PLUS and FlowVPX® Systems bring variable pathlength UV/Vis technology to critical analytical points in the process. SoloVPE PLUS enables fast, at-line analysis of protein concentration and ADC-related measurements without dilution, while FlowVPX extends VPT-based UV/Vis measurement in-line to support process-connected monitoring of concentration and DAR during conjugation, purification, concentration, and formulation. Together, PATsmart technologies help reduce reliance on slow, manual, off-line methods while supporting faster process decisions, improved consistency, and safer workflows when working with complex and highly potent ADC materials.
Antibody–Drug Conjugate Manufacturing: Driving Process Productivity and Reducing Risk
ADC manufacturing remains a complex, multi-step process with inherent challenges. Both early- and late-stage manufacturers must navigate the intricacies of handling highly potent payloads, maintaining consistent drug-antibody ratios (DAR), minimizing operator exposure, and ensuring product efficacy and safety. Hear from expert Field Applications Scientists as they discuss technologies that can help to:
- Accelerate processing time
- Maintain product consistency and operator safety
- Drive efficiency with accurate, real-time DAR measurement
Start the Journey: Achieving Safety, Efficiency, and Flexibility in ADC Manufacturing
From theory to therapy- Immerse yourself in the world of antibody-drug conjugates (ADCs) in our latest white paper. Learn about the anatomy of ADCs, unique manufacturing challenges, and the critical role of single-use systems in ensuring safe, efficient, and flexible production processes. Glean insights and discover the operational advantages Repligen Tangential Flow Filtration systems and Chromatography systems offer to ADC manufacturers.
Dig into the Data: Extractables Study on Single-use Consumables for ADC Production
When adopting single-use systems for ADC manufacturing, added emphasis is placed on the risk of extractables and leachables (E&L) from the flow kits and membranes. These substances, which may be released under certain conditions, could potentially impact the safety and efficacy of the final product. Our study delves into this concern, evaluating E&L from ProConnex® Flow Paths and TangenX® SIUS Gamma Cassettes, particularly in the presence of common solvents like dimethyl sulfoxide (DMSO) and dimethylacetamide (DMAC).
Analyze the Findings: Validation of ADC Platform for Drug-Antibody Ratio (DAR) using Variable Pathlength Technology
Critical to the design and evaluation of ADCs during formulation, Drug-Antibody Ratio (DAR) refers to the number of drug molecules attached to the antibody. But with several DAR measurement methods to choose from, which provides the greatest degree of accuracy and actionable insights? Discover the superiority of the variable pathlength technology that powers our PATsmart SoloVPE® PLUS and FlowVPX® systems in this insightful analytical review.
Collaborate with Confidence: Review of Single-Use Flat Sheet Cassettes in ADC Processing with Sanofi
When it comes to ADC purification, performance matters. Discover how Repligen’s TangenX® ProStream™ and HyStream™ tangential flow filtration (TFF) cassettes deliver high-efficiency output across critical ultrafiltration and diafiltration steps in ADC production. Developed in collaboration with Sanofi, this in-depth study showcases real-world data on solvent clearance, membrane integrity, and product recovery.
