LAUSR

Biologics are protein-based drug products (DP) used as therapeutics. To date, more than 60 biologics are commercially approved for use as therapeutics in various malignancies. More than 1300 other biologics candidates are in clinical development, and the number of products and clinical candidates is expected to almost double by the year 2025. Typically, these modalities target therapies for oncology, transplant rejection, autoimmune and infectious diseases, as well as a range of other indications. A number of monoclonal antibody products have been developed and marketed over the last decades. Today, more modern and rationally designed biologics including fusion proteins, bispecifics and immune-oncology therapeutics are under development. Protein therapeutics show several advantages over small molecule drugs. Proteins are highly specific and can ensure sufficient targeting. A major disadvantage of biologics is the need to administer them by parenteral administration, that is injection or infusion, to ensure systemic delivery. Additionally, these molecules may trigger immune response in patients which may or may not be clinically relevant and either negatively impact efficacy or may be a safety liability. The development and production of biologics are very challenging due to both the complexity of fermentation, purification, formulation and drug product manufacturing, as well as their limited physical and chemical stability, which can be often directly related to the molecule’s structure. Within this issue, we would like to introduce the topic of immunogenicity assessments of protein therapeutics. A significant part of the issue is dedicated to the attempt to design and screen for the best possible protein structure early, including biopharmaceutical informatics, evaluations of surface property on protein stability and high-throughput screening for oxidation or solubility (aggregation tendency). While aggregation has been a hot topic for R&D scientists, protein oxidation has not received sufficient attention in the past, although it may impact pharmacokinetics or immunogenicity of protein therapeutics. Another chapter is thus dedicated to tryptophan oxidation specifically. Unlike small molecule therapeutics, where drug/drug combination therapies are common, the combination of two proteins in one dosage form seems to be rather exceptional and will be discussed in another part of this issue. Finally, to highlight specific challenges in drug product processing, the influence of particle shedding on antibody stability is discussed. In summary, biologics provide exciting therapeutic options, yet, pose specific challenges that need to be addressed by adequate product and process design. I hope you will enjoy this issue to dive a bit deeper into this exciting field.