Antibody Drug Conjugates (ADC)

Full mammalian upstream and downstream to purified mAb intermediate — as described in our Mammalian Cell Culture area. Chain of identity maintained through MES from WCB through to the conjugation suite.

Buffer exchange into conjugation buffer, concentration verification and temperature conditioning — DCS-controlled hold with MES batch record. Controlled addition of reducing agent (TCEP or DTT) to generate free thiol groups for cysteine-directed conjugation — DCS manages addition rate, temperature and hold time with precise alarm limits, because the degree of reduction directly determines the DAR distribution of the final product.

Drug-linker payload dissolved in organic solvent is added at a controlled molar ratio to the reduced antibody — temperature, mixing, addition rate and reaction time all controlled through DCS within a closed containment system. Where microfluidizers or high-shear homogenisers are part of the process — used to achieve homogeneous mixing of the aqueous and organic phases without protein aggregation or localised concentration spikes — we integrate them into the DCS control architecture. MES records every in-process parameter against the validated batch record. The conjugation reaction is where DAR distribution is set and where a control deviation cannot be corrected downstream.

Quenching agent addition at controlled rate and hold time — DCS-controlled, MES-recorded. Immediately followed by containment-critical TFF to remove organic solvent from the post-conjugation material. DCS controls transmembrane pressure, flux and permeate flow; MES records diavolumes and conductivity targets. The post-conjugation stream contains free drug and the automation must ensure no operator exposure through a process gap.

ADC downstream purification is more complex than standard mAb downstream because the process must separate DAR species, remove unconjugated antibody, clear free drug and linker and remove aggregates — all under containment. The specific capture resin and polishing sequence is process-dependent; typical configurations run capture chromatography followed by HIC for DAR species separation, CEX for aggregate and charge variant removal, AEX for polishing, viral filtration under containment, and final UF/TFF for concentration and formulation buffer exchange. Our Process Automation Engineers configure each step as an integrated DCS sequence — gradient control, UV monitoring, pressure alarm management and automated pooling decisions — with MES tracking acceptance criteria across every column. Pooling decisions that determine DAR homogeneity are built into the recipe logic, not left to operator interpretation.

Depending on the ADC formulation requirements, high-shear processing equipment including microfluidizers or homogenisers may be used to achieve uniform particle size and payload stability in the final drug substance. We integrate these into the DCS control framework — pressure, temperature, number of passes and in-process monitoring — with MES recipe management and full batch recording through to bulk drug substance filling and frozen storage.

ADCs are filled as liquid or lyophilised depending on the product stability profile. Both are performed under containment. For lyophilised ADCs, DCS controls the full freeze-drying cycle — shelf temperature, chamber pressure, primary and secondary drying, end-point determination — with MES managing the lyophilisation recipe and cycle documentation. Lyophilisation of ADCs presents specific challenges around payload stability during the freeze-drying process; our Process Automation Engineers understand those constraints and build them into the cycle control logic from the outset.