Oncobiologics Inc. is a biotech company in Cranbury, New Jersey focusing on biosimilar development. They have a good pipeline of products in development, including some in clinical evaluation, and two having successfully completed phase 1 evaluation.
Jessica Cheung, Scientist II, Maria Taddei, Senior Scientist II, and Hiten Gutka, Ph.D., Principal Scientist, are all in the Formulation Development group at Oncobiologics Inc. Their primary role is to develop stable biopharmaceutical formulations, and also explore innovative formulation conditions to improve product attributes. For example, they may work to identify conditions where aggregation of proteins can be reduced, or conditions where subvisible particles are lower than the reference product.
Reference products are all blockbuster biologic drugs that were approved for therapeutic use about 10-12 years ago. Technology has changed greatly since then and regulatory expectations will be very different in the future. “When these drugs were formulated, developed, and the clinical evaluations were done, the technology to look at protein aggregates and particles was very limited,” says Hiten. “Back then, size exclusion chromatography was the gold standard for evaluating protein aggregation.”
There have been several guidance documents issued on sub visible particles in protein pharmaceuticals in the recent past. With the changing regulatory expectation, the industry needs to identify new technologies for characterizing visible and subvisible particles, and protein aggregates. This is what Hiten and his team are doing right now – they are helping Oncobiologics build their own toolbox of technologies to analyze and characterize particles in their biosimilar product formulations to be prepared for the new regulations.
In reading research and white papers, they found that the FlowCam® dynamic imaging particle analysis instrument from Fluid Imaging Technologies matched the most critical aspects they were looking for in a new technology – image quality and fast data analysis. Instrument sensitivity was also high on the list because protein aggregates are transparent which makes it challenging to identify and characterize them. The scientific team at Oncobiologics got in touch with Fluid Imaging and scheduled a demonstration of the FlowCam. During their assessment, they got some very exciting data. They also learned that the image quality and the data analysis after the image acquisition was exceptional.
In any particular project, the team evaluates all possible known protein stabilizers, which are permissible in terms of intravenous and subcutaneous administration of biologic drugs. They try to identify conditions where the stability of the antibody therapeutics are enhanced. There are certain tools, like light scattering (DLS/SLS), multi-angle light scattering (MALS), and differential scanning calorimetry (DSC) that help to get a good assessment of how these antibodies are behaving in different formulation conditions. These formulation conditions are picked, chosen and subjected to stability tests like shaking stress, or temperature stress which might be encountered during the normal life-cycle of a drug product. These things can happen during manufacturing, storage, or dispensing at the pharmacy.
With its VisualSpreadsheet® software, the FlowCam can record over 30 different measurements per particle and can capture particle images at up to 22 frames per second which quickly provides Hiten with the answers he needs. He says that anything in the range of 2-100 microns that resembles a protein is differentiated from silicone oil in his formulations. Besides the visual evaluation, the FlowCam instrument also provides the possibility to differentiate rubber, glass or fiber particles. “This instrument has helped out immensely in differentiating silicone oil particles with anything which is related to product,” says Hiten. “Having an image library to reference is a big milestone in protein characterization.”
The next issue, in addition to characterization, is providing a risk assessment of immunogenicity potential of such particles. This is where the industry is moving. If you have a method to identify and characterize these particles, then you can come up with a risk assessment, and a risk mitigation approach.
“If I was to equate this tool to something which significantly changed some people's lives worldwide, it was the invention of the steam engine. The FlowCam is synonymous to that in the subvisible particle characterization world, seeing particles is a major advantage” states Hiten. “With this instrument, we are getting the images and data to help us answer questions about our formulations. We now know particle shape and morphology in addition to the count, and that’s a real game changer.”
You can also download our eBook, The Ultimate Guide to Dynamic Imaging Particle Analysis for Protein Therapeutics.