Almost as fundamental as discovering the ideal biopharmaceutical candidate is developing a robust and protective bioformulation which will enable the precious molecule to remain stable and permit safe, comfortable delivery to the patient. Bioformulation development is a lengthy and iterative process beginning with the early physicochemical analyses of preformulation, all the way to perfecting formulations in clinical studies.
Within preformulation in particular, the characterization of a molecule’s physical, chemical and mechanical properties must take place in order that an initial recipe of excipients can be prepared, and immediate issues with the potential drug product identified as early as possible. Accelerated stress tests are often carried out on a bioformulation to understand the behavior of the product under a range of conditions such as temperature, pH, pressure and shear stress, along with freeze/thaw iterations. These investigations will rapidly identify any tendency of the biotherapeutic molecule to degrade, unfold or aggregate, and provide an opportunity for the “fail early, fail cheap” mantra to be brought into play. Later in formulation studies, such factors as polymorphism, solubility and particle size are considered in terms of their effects on stability, bioavailability, activity and safety.
Malvern’s real strength in biopharmaceutical analysis lies within the formulation arena, and we have a wide range of innovative products and associated expertise to help you mitigate your formulation risks as simply and rapidly as possible. The new Viscosizer TD is a perfect example of this, with its ability to accurately measure formulation viscosity at discovery-phase low sample volumes, with the automated high throughput required for the large numbers of samples to be measured at this stage in development. Archimedes permits both measurement and quantification of early products of aggregation, and also allows complete differentation of protein aggregates from contaminants such as silicone oil, a major consideration in container closure testing.
It is vital that biopharmaceutical molecules are formulated to the correct oligomeric state (molecular weight), with few or no aggregates present. Malvern’s Viscotek GPC/SEC systems can be used to measure a protein's oligomeric state to ensure it is correct and gain insight into its structure, enabling quick, accurate assessment of formulation suitability. Additionally, any aggregation that occurs can be quantified and characterized (molecular weight and structure). The Zetasizer range of products enable real-time monitoring of aggregation to understand the molecule's behaviour in formulation. The newest recruits to Malvern's range of biopharmaceutical solutions, the Nanosight series of instruments, provide both qualitative and quantitative real-time information on polydisperse aggregate presence in formulations.
Bioformulations that show less or more gradual aggregation can be inferred to be more stable and more suitable for onward development.
Recognizing the likely degradation routes of your molecule early on is paramount for rapid development of the protein therapeutic and is a requisite for the determination of stability-indicating analytical methods. Malvern’s solutions to assist with formulation studies are anchored firmly on the product/process knowledge or intended usage and are designed to understand the physiochemical and biophysical properties chemistry of your molecule and related impurities.