Sub Topic | Secondary Topic: Biotherapeutics and Biotechnology - Biosimilar | Bioequivalance
Authors: Shantaveer Irappanavar, Suven Life Sciences Ltd. (Main Author, Presenting Author); Venkatesh Kamuju, Suven Life Sciences Ltd.; Sudhakar Gandipudi, Suven Life Sciences Ltd.; Vijay Benade, Suven Life Sciences Ltd.; Nageswara Muddana, Suven Life Sciences Ltd.; Ranjithkumar Ponnamaneni, Suven Life Sciences Ltd.; Arunkumar Manoharan, Suven Life Sciences Ltd.; Gopinadh Bhyrapuneni, Suven Life Sciences Ltd.; Ramakrishna Nirogi, Suven Life Sciences Ltd.
Presenting Author: Shantaveer Irappanavar
Purpose: The objective of the current study was to demonstrate the utility of preclinical models for pharmacokinetic and pharmacodynamic evaluation of ophthalmic formulations in 505(b) (2).
Methods: <B>Animals:</B> Male New Zealand Albino rabbits (2-2.5 kg). <B>Serial sampling of aqueous humor:</B> Test formulation (30 µl) was instilled topically into the inferior cul de sac of the eye and aqueous humor was collected at different time intervals after lignocaine anesthesia. <B>Models for Glaucoma:</B> 1. Intraocular pressure (IOP) measurement in normotensive rabbits- Animals were anesthetized with topical administration of lignocaine and IOP readings on the central cornea were measured unilaterally using Pneumatonometer. Measurements were done at predose (0 h) and different time point post treatment. 2. IOP measurement in ocular hypertensive rabbits- Unilateral ocular hypertension was induced after 3 weeks of α- chymotrypsin intracameral injection. <B>Models for Ocular Inflammation:</B> 1. Measurement of inflammatory biomarkers- Aqueous humor sampling was done post treatment of test compound and inflammatory biomarkers like prostaglandin E2, Interleukin-1β were measured post treatment. 2. Vitreous Haze- Vitreous haze was induced by the intravitreal injection of lipopolysaccharide from E. Coli. The Contralateral eye served as a control. Inflammation was evaluated by clinical observation of iris and conjuctival hyperemia.
Results: Moxifloxacin appeared rapidly in the aqueous humor and the test formulation was observed to be bioequivalent to the reference listed drug. Effect of bimatoprost on ocular IOP: Topical administration of test formulation of bimatoprost produced decrease in IOP compared to control and test formulation was observed to be bioequivalent in normotensive and hypertensive rabbits. Daptomycin produced significant decrease in the inflammatory biomarkers and the vitreous haze.
Conclusion: FDA does not require strict demonstration of human bioequivalence and pharmacokinetic assays as this would require invasive ocular procedures. Thus, preclinical models can be effectively used for screening of ophthalmic formulations for 505(b) (2).
See attached abstract pdf for images.