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Antibody Drug Conjugates (ADCs)

Custom Approaches to Antibody Drug Conjugates

Targeted therapeutics, including antibody-drug conjugates (ADCs) and polymer-drug conjugates, represent a growing market segment, but face unique challenges during research and development due to their structure and complex chemistries. Despite advances in protein engineering, conjugates are highly heterogeneous. Intrinsic heterogeneity significantly affects the complexity of the discovery and development pathway. Fortunately, our experience across small molecules and biologics provides a comprehensive background well suited to the development of ADCs and other polymer-drug conjugations. Our development facilities offer the full component of analytical tools and resident expertise and also the appropriate environmental controls and procedures to safely handle highly potent compounds.

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Comprehensive Molecular Support

Analytical Characterization

Analytical characterization plays an important role in ensuring product integrity and manufacturing consistency, which are essential for demonstrating drug safety and efficacy. However, the heterogeneity of ADCs makes analytical characterization particularly challenging. The selection of appropriate analytical techniques depends on the properties of the linker, the drug, and the choice attachment site. Our team uses numerous orthogonal analytical methods to characterize ADC physicochemical and biophysical properties, including high resolution mass spectrometry-based techniques, chromatographic techniques, electrophoresis, particulates analysis, and hybrid techniques.

Physicochemcail & Biophysical Characterization

Our characterization screening leverages a fundamental understanding of conjugate chemical and biophysical behaviors and how these are impacted by drug load. The formation of aggregates is a common degradation mechanism, so assessing the propensity for self-association is a critical parameter to enable efficient and effective formulation development.

While reversible association is generally less problematic than irreversible association, high concentration and formulation conditions such as pH and ionic strength can alter the equilibrium toward the formation of irreversible aggregates. Early assessment of the propensity to form reversible and irreversible aggregates significantly contributes to developing appropriate analytical techniques in advance.

Various mechanical stresses during sample preparation and manufacturing process have the potential to induce conformational changes leading to loss of activity, adsorption, aggregation, and precipitation. Understanding which stressors cause instability directly affects sample handling, formulation, and process development. We develop mechanism-based approaches to stabilize the molecule with knowledge of the degradation pathways at different pH values. Aside from the logistical need to prevent degradation, instability caused by storage or process conditions compromises the accurate interpretation of studies during development.

Formulation & Process Development

After determining formulation boundaries with solubility, stability, and target pH parameters, our team drives forward with formulation and process development in tandem. We optimize your formulation through a series of experiments and define robustness with a Design of Experiment (DOE) approach. Our team also conducts discrete studies when appropriate. The resulting samples are assessed under accelerated stress conditions to select the most stable formulations with sufficient solubility. As a result of these experiments, we develop a stable formulation with the desired TPP when placed on long-term stability.

Integrated Laboratory Services  

When your team needs additional CDMO support, our scientists are ready. Our state-of-the-art facilities and highly trained experts can add power to your project.