Protein self-interactions are an intrinsic behaviour that can adversely affect the developability of therapeutic proteins. Our recent work on NMR-based interaction & behaviour assessments permits the simultaneous detection of weak protein-protein and protein-excipient interactions. We discuss applications to protein formulation optimisation, de-risking mAb co-formulations, candidate developability assessments as well as residue-level structural details that can guide protein design.

Progress in drug design has led to the development of new peptides, proteins, and drug molecules. However, the limited ability to selectively deliver these molecules at well-defined dosing regimens remains a significant challenge. These challenges can be bypassed by using novel technologies such as 3D Printing/Bioprinting. Various designs with high drug payloads that formulated by 3D printing and characterised using advanced characterisation techniques (e.g. μCT, ToF-SIMS) will be discussed.

Cell line development includes the screening of thousands of clones. The aim is to find the few that are stable, grow as expected, and produce high yields of the bioproduct.  Speed up antibody discovery and development by moving higher quality candidates downstream. How? Carry out expression level analysis label-free in crude samples. Combine it with early-stage glycan characterization both in a high-throughput mode.

With growing competition in the market and patient-centric product strategies, the demands for product differentiation are increasing. Innovative formulation together with appropriate device strategy is key in achieving such differentiation. This talk will demonstrate on several case studies how novel formulation principles can be used to develop products with superior stability with clear benefits for the patient, as well as leading to new patent applications extending the product exclusivity.

Distinguishing aggregated API from other particle types is important for understanding the root cause of instability. Existing methods are unreliable, too cumbersome and difficult to use in many workflows. With Aura, you can now finally count, size, and characterize aggregates and identify them as proteins, non-proteins, or other molecules.

Biologics are labile molecules and are prone to aggregation. I will review our experience with model biologics, comparing the impacts of formulation and process on aggregate levels. Freeze drying can mitigate aggregation by delivering a stable format for long term storage and optimisation in terms of excipients used and freeze-drying cycle design will be presented. The value of Design of Experiments and high-throughput screening in optimising formulation will be described.

A key stumbling block towards predicting and controlling aggregation is isolating properties of partially folded or unfolded intermediates in the pathways.  Here, we present a few examples, covering monoclonal antibodies and antibody fragments, where we have measured the association behaviour of unfolded intermediates using chemically denaturing conditions.  The results provide insight into key structural properties controlling aggregation propensity and how excipients alter different steps in the aggregation pathways.

Dipicolinic acid (DPA) is a small organic molecule that comprises 10-15% of the dry weight of spores and is involved in spore stability and resistance to wet heat. The application of DPA as a pharmaceutical excipient is somewhat hampered by its low aqueous solubility. Through counterion screening studies, we discovered two novel salts of DPA, ethanolamine-DPA and diethanolamine-DPA, which showed improved solubility and significantly reduced the viscosity of high concentration mAb formulations.

Adenoviral vectors used in vaccine development are challenging study objects due to their complex composition of viral proteins as well as viral and transgene DNA. Determining routes of degradation is part of the stability strategy. Stability studies performed based on ICH guidelines in development are indented to define the shelf life. By additionally applying characterization methods to aged or stressed samples the route of degradation can be studied in more detail.

The talk will document the importance of using different orthogonal analytical methods to assess the similarity of originator products and biosimilar drug candidates. Case statues will include development projects and products such as bevacizumab and pegfilgrastim.

Batch variation can be a major problem for drug product stability and early knowledge of critical quality attributes (CQAs) and degradation mechanism can be essential to reduce/avoid challenges related to Chemistry, Manufacturing and Controls (CMC) processes at a later stage. In the current case study, it is highlighted how oxidation can affect product stability, and thus product quality for a complex product containing six different monoclonal antibodies.

The self-assembly and aggregation of proteins during production and storage can produce assemblies with sizes ranging from nanometres to micrometres. I will discuss how the physio-chemical characteristics of a protein can influence formulation stability and will discuss the challenges associated with development and analysis of high concentration formulations.