Simplified strategy for developing purification processes for antibody-drug conjugates using cation-exchange...

Area of Science:

• Biopharmaceutical Manufacturing
• Protein Chemistry
• Chromatography

Background:

• Manufacturing antibody-drug conjugates (ADCs) poses unique challenges compared to standard monoclonal antibodies.
• ADC processing introduces hydrophobic molecules and co-solvents, leading to increased protein aggregate formation.
• A post-conjugation purification step is often essential for robust ADC production meeting quality specifications.

Purpose of the Study:

• To develop a robust chromatographic purification methodology for removing very high molecular weight species (vHMWS) in ADCs.
• To streamline the development of purification steps by leveraging existing antibody intermediate purification conditions.
• To demonstrate the efficacy of the developed method across multiple ADC products.

Main Methods:

• Development of chromatographic purification steps tailored for ADC products.
• Application of flow-through cation-exchange chromatography.
• Utilizing conditions from prior antibody intermediate purification to accelerate method development.

Main Results:

• Successfully reduced very high molecular weight species (vHMWS) by at least 85% in three ADC products.
• Achieved final vHMWS levels of ≤ 0.1% post-purification.
• Demonstrated efficient and robust development of cation-exchange chromatography steps.

Conclusions:

• A streamlined methodology for developing chromatographic purification of ADCs was established.
• Flow-through cation-exchange chromatography is an effective strategy for removing vHMWS in ADCs.
• This approach ensures robust production of high-quality ADC products with reduced aggregates.