Bill McDowell heads up the Abzena Cambridge Analytics group overseeing the group’s protein characterization, developability and formulation development activities. He has over 20 years’ experience of early-stage drug development in pharmaceutical R&D at GSK, supporting programmes targeting malaria, tuberculosis, AIDS, influenza, RSV, hepatitis C, Complement and other anti-inflammatory targets. Prior to GSK, Bill had 11 years in post-doctoral research in Germany and the MRC in London. His background is in protein biochemistry particularly protein glycosylation and mass spectrometry.
Bill joined Abzena in 2014 as a Team Leader in Bioconjugation and Analytical Chemistry and has been in his present role since 2017 being promoted to senior director in 2022.

Abstract

The development of biologics, like monoclonal antibodies (mAbs), Antibody-drug conjugates (ADCs) and bispecific antibodies, has provided treatment for diseases once deemed untreatable, such as advanced cancers and autoimmune disorders. As powerful as these biologics are, their development still come with substantial technical challenges.
Behind every biologic drug is a formulation that ensures the molecule’s stability, safety and efficacy. This unassuming yet critical component must handle the inherent complexity of biologics and their sensitivity to environmental factors like pH and temperature, while maintaining efficacy and manufacturability at scale. Increasingly, formulation efforts also address a key patient-centric need: transitioning therapies from intravenous (IV) to subcutaneous (SC) formats. High-concentration formulations are central to SC delivery, but they introduce new technical hurdles that demand a great deal of expertise.

Challenges in biologic drug formulation

Physicochemical complexities
Biologics are inherently sensitive to their environment due to their large, complex molecular structures. Changes in temperature, pH and mechanical agitation can destabilize these molecules, leading to aggregation, degradation or precipitation. These issues can cause irreversible damage to the product with a subsequent loss of therapeutic efficacy or inducing adverse effects in patients.

Aggregation remains one of the most common challenges in biologic formulation. Aggregation not only reduces the potency of the biologic but also poses a significant risk of triggering adverse immune reactions. These aggregates often form due to weak intermolecular forces that become pronounced during storage or under stress conditions such as agitation during transport or freeze-thaw cycles.

Another issue is viscosity. At higher concentrations – often required for SC delivery – viscosity can increase exponentially with protein concentration.
This elevated viscosity presents challenges for drug delivery, as it can ex ...