Ophthalmic Product Development for Biologics

Due to the complex and unique anatomy and physiology of the eye, the delivery of therapeutic agents to the back of the eye remains a major challenge. The National Eye Institute estimates that the number of people affected by severe ophthalmic diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) will double by 2050, creating approximately US$139 billion economic burden associated with eye diseases alone. This presents a growing need for improved therapeutic agents for the treatment of eye disorders. The current paradigm for the treatment of diseases is shifting toward biologics that show higher specificity in comparison to the conventional small molecule therapeutics. However, the delivery of biologic molecules has specific challenges including, for example, limited stability and poor penetration across biological membranes. Adding to the difficulty of resolving these issues is the lack of preclinical models for assessing safety and pharmacokinetic profile of the formulations. An additional challenge specific to intraocular drug delivery includes the strict volume limitation for intraocular delivery, which necessitates the need for high concentration formulations and drug-device combinations in order to deliver an efficacious dose of the drug. These high concentration biologic formulations may pose additional challenges associated with high viscosity, insufficient drug solubility, product manufacturing, storage, and handling, as well as challenges to drug administration. In addition, many of the common GRAS listed excipients used to stabilize or mitigate viscosity in biologics have not been evaluated for use in ophthalmic preparations. This chapter highlights some of the formulation development and stability challenges faced by pharmaceutical scientists during the development of ophthalmic biological products and summarizes some current, relevant regulatory guidance.