Protein stability is one of the major challenges in pharmaceutical development. Throughout the drug manufacturing, storing, and administration processes, therapeutic proteins will move through containers such as concentrators, tubing, bags, and vials made of several different materials, such as: glass, oils, plastic polymers, and metals. As proteins come in contact with these surfaces, they can adsorb and unfold.
To ensure a fully functional drug and to minimize protein loss, characterization and understanding of protein interaction with surrounding surfaces is an important and valuable insight. This information can be gathered using Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), a technique which enables real-time analysis of molecular interactions and surface properties.
The QSense QCM-D systems are versatile, offering a wide variety of sensors and modules to help answer your complex research questions about protein interactions with various surface materials and at different solution conditions. This level of versatility makes QSense the best QCM-D systems for experiments such as:
- evaluating material compatibility
- identifying conditions that minimize protein adsorption
- understanding and minimizing surface-induced protein aggregation
Below you will find a collection of knowledge and insights from this field of research, including application notes, webinars, blog posts, and case studies. These resources include both academic and industrial examples of how QSense QCM-D systems have been used to monitor therapeutic protein interactions with the goal of optimizing the development of therapeutic protein drugs at several points in the product life cycle–from formulation to its final packaging/storage container before being administered.
Use QCM-D to monitor protein adsorption on common materials used during protein production
Proteins have a tendency to passively adsorb to such surfaces via hydrophobic interactions, a phenomenon that has to be minimized or prevented in, for example, large-scale recombinant protein production. In this application note, QCM-D is used as a real-time screening tool for protein adsorption onto PVDF and borosilicate.
Impact of material and concentration on characterizing protein adsorption to glass and plastics with QCM-D
The amount of protein adsorbed depends on many factors such as the protein itself, the ambient conditions and the surface material. So how can we assess the adsorbed amount at these various conditions? We used QSense QCM-D, a surface sensitive real-time technology that monitors mass changes at the surface.
Use QCM-D to analyze and quantify how excipients and surfactants affect therapeutic protein adsorption
The inherent surface-active nature of proteins can cause them to interact with surfaces, leading to possible denaturation and subsequent aggregation. This aggregation can produce safety related issues like unwanted immune responses, undesired cross-reactivity, or loss of efficacy.
Excipients are additives to a protein formulation that help to stabilize the protein’s structure and minimize any potential unwanted aggregation cascade. They can range from simple buffers to more complex components such as amino acids, sugars, surfactants, and antioxidants. Surfactants, or surface active agents, play a major role in determining how a protein will interact with a surface through three possible mechanisms… Read on for more
The behavior of therapeutic proteins in solution is generally well characterized, but the adsorption to, and interaction with, various surface material is often not studied. Studying protein interaction with various surface materials and at different solution conditions, the material compatibility can be evaluated and conditions that minimize adsorption can be identified. Here we show you one way to do this assessment.
Use QCM-D to analyze monoclonal antibody (mAb) aggregation at oil-water interfaces such as prefilled, lubricated syringes
In the four studies presented in this case study, QSense technology was used to analyze and quantify the adsorption of therapeutic monoclonal antibodies and proteins to different materials and interfaces. In addition to the impact of the material, the effect of sample concentration and presence of surfactants on the surface uptake was also characterized and quantified.
A common way to store and administer therapeutic protein to patients is via prefilled glass syringes. Silicone oil, which is used as a syringe lubricant, could induce protein loss, but the addition of surfactant has been shown to reduce such loss. The study discussed here has been conducted to gain a deeper understanding of why this is the case.
One of the major challenges in pharmaceutical development is protein aggregation – a phenomenon that could have a negative impact not only on the drug quality, but could also potentially affect drug safety. In a recent study, results are presented that provide a deeper understanding of the relation between protein adsorption and aggregation at the oil-water interface. The new insights could help designing more stable therapeutic formulations, and QSense QCM-D was one of the analysis methods that helped piece the puzzle together.