Phase-Appropriate Application of Analytical Methods to Monitor Subvisible Particles Across the Biotherapeutic Drug Product Life Cycle.

The phase-appropriate application of analytical methods to characterize, monitor, and control particles is an important aspect of the development of safe and efficacious biotherapeutics. The AAPS Product Attribute and Biological Consequences (PABC) focus group (which has since transformed into an AAPS community) conducted a survey where participating labs rated their method of choice to analyze protein aggregation/particle formation during the different stages of the product life cycle. The survey confirmed that pharmacopeial methods and SEC are the primary methods currently applied in earlier phases of the development to ensure that a product entering clinical trials is safe and efficacious.

The missing piece in the puzzle: Prediction of aggregation via the protein-protein interaction parameter A.

The tendency of protein pharmaceuticals to form aggregates is a major challenge during formulation development, as aggregation affects quality and safety of the product. In particular, the formation of large native-like particles in the context of liquid-air interfacial stress is a well-known but not fully understood problem. Focusing on the two most fundamental criteria of protein formulation affecting protein-protein interaction, the impact of pH and ionic strength on the interaction parameter A and its link to aggregation upon mechanical stress was investigated.

Impact of formulation pH on physicochemical protein characteristics at the liquid-air interface.

Both, formulation parameters and the presence of liquid-air interfaces are known to affect the aggregation of protein drugs. In this study, the impact of pH on the liquid-air interfacial behavior of three proteins, a polyclonal and two monoclonal antibodies (IgG, mAB and mAB) was investigated using different surface sensitive methods. Equilibrium surface pressure values revealed only a minor impact of pH.

Notorious but not understood: How liquid-air interfacial stress triggers protein aggregation.

Protein aggregation is a major challenge in the development of biopharmaceuticals. As the pathways of aggregation are manifold, good understanding of the mechanisms behind is essential. Particularly, the presence of liquid-air interfaces has been identified to trigger the formation of large protein particles.

The film tells the story: Physical-chemical characteristics of IgG at the liquid-air interface.

The presence of liquid-air interfaces in protein pharmaceuticals is known to negatively impact product stability. Nevertheless, the mechanisms behind interface-related protein aggregation are not yet fully understood. Little is known about the physical-chemical behavior of proteins adsorbed to the interface.

A prospective three-step intervention study to prevent medication errors in drug handling in paediatric care.

Aims And Objectives: To prevent medication errors in drug handling in a paediatric ward.

Background: One in five preventable adverse drug events in hospitalised children is caused by medication errors. Errors in drug prescription have been studied frequently, but data regarding drug handling, including drug preparation and administration, are scarce.