Protein crystallization as a mechanism for biosimilar formulation

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Apobiologix, a division of Apotex, is a market leader in the production and distribution of biosimilars. Biosimilars are complex biological molecules, such as proteins or antibodies, which are highly similar to other biological products already on the market. In order to bring a protein to market, it needs to be prepared and stabilized in a process known as formulation. In an effective formulation a protein is required to be at a high concentration, however this can lead to undesirable increases in viscosity, abnormal protein aggregation, precipitation, degradation, or loss in stability, all of which are undesirable. An alternate approach to increase a protein's concentration is through crystallization; protein crystals are semi-solid (unlike salt crystals), and therefore maintain a very large protein concentration without the drawbacks of simply adding more protein to the solution. However, crystallization of each molecule requires unique conditions that must be determined through an empirical investigation of screening and optimization prior to stabilization of the crystals for downstream formulation processes. Apobiologix does not have in-house expertise in protein crystallization, and has therefore partnered with York University to identify and optimize a framework for protein crystallization as a mechanism for biosimilar formulation. The research outlined in the current application seeks to determine a crystallization and stabilization framework for a recombinant human growth hormone (rhGH) biosimilar. Research will focus on identifying multiple crystallization conditions for rhGH that will then be optimized to scale, while ensuring the long term stability of the rhGH crystals in formulation solutions. Crystallized and stabilized rhGH can then be moved into the biosimilar product pipeline at Apobiologix, resulting in bringing this protein biosimilar to market. With the support of this proposal, we aim to (1) develop an on-going research partnership between Apobiologix and York University, and (2) foster future research into the crystallization of biosimilars for product development.