Non-GLP sample analysis for ocular biodistribution studies
Traditional bioanalytical service providers are geared toward analyzing large sets of samples under various regulatory guidelines, such as large nonclinical and clinical studies, which are heavily regulated. This puts a heavy burden on these service providers, creating long lead times, resource constraints and lack of flexibility. Currently, many bioanalytical laboratories report lead times of six to nine months to begin development work. These limited bioanalytical options are causing extensive delays in overall drug development affecting the finances of sponsors.
Exacerbating the above situation, some specific studies involve small sample sizes (<100), non-routine matrices and no set regulatory requirements. The already resource-constrained bioanalytical providers are unable to accommodate these study types, leaving sponsors—specifically those biotechs lacking wet labs—with even fewer options. This necessitates the emergence of a niche provider with experience handling various matrices designed to run small numbers of samples efficiently with short turnaround times (less than one month).
At our Denver, Pennsylvania, site, we have more than 45 years of experience in offering antibody generation, vaccine testing services and non-GLP sample analysis to the drug development industry. Our business unit is uniquely positioned to analyze small numbers of samples with a very short lead time due to our focus on discovery and research and development phases of the drug development process. This allows us to quickly develop or qualify an existing assay or commercial kit and measure the analytes in various matrices including ocular tissues. The case study below highlights our experience and capabilities in this area.
Non-GLP sample analysis of ocular biodistribution study
Anatomical barriers that separate the eyeball from general circulation make it necessary for certain drugs to be applied either topically or administered into subocular tissues. Once the drug is applied, various ocular tissues are collected and the biodistribution of the drug is determined by various methods. Due to availability of ocular tissues in very small quantities and the rare nature of these matrices, the bioanalytical methods used are generally conducted under non-GxP environments. Here, we describe an example of such a study in which a biosimilar to Lucentis® was tested in primates by ocular administration.
A commercially available VEGF protein was coated on the plate to capture the biosimilar from various ocular matrices and the bound drug molecule was detected with an HRP-labeled anti-human kappa light chain antibody. The method was qualified for each matrix and a minimum required dilution for each matrix was determined by a spike recovery approach. The following results represent a typical distribution of a biotherapeutic injected into the intravitreous portion of the eye.
Concentration of biosimilar in various ocular tissues (ng/mL) 24 hours post intraocular administration
AH, aqueous humor; BQL, below quantitation limit; VH, vitreous humor
The above results clearly indicate that the therapeutic drug when administered via the intravitreous route distributes broadly to other ocular tissues and remains available to act at the target site. In addition, the results show that this therapeutic does not reach systemic circulation when administered through the ocular route. The full kinetic data helped the sponsor decide on the dosing regime and further development of the biosimilar. Our business unit’s ability to quickly develop the needed assay and analyze the samples with a faster turnaround time allowed the sponsor to meet their timelines for regulatory submission.
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