June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Determination of a No Observed Effect Level (NOEL) for Beta Glucans following a Single Intravitreal Administration to Female Dutch Belted Rabbits
Author Affiliations & Notes
  • Vladimir Bantseev
    Genentech Inc, South San Francisco, California, United States
  • Sara Parker
    Genentech Inc, South San Francisco, California, United States
  • Roxanne Andaya
    Genentech Inc, South San Francisco, California, United States
  • Chris Schuetz
    Genentech Inc, South San Francisco, California, United States
  • Brian Christian
    Toxicology, Covance Inc, Princeton, New Jersey, United States
    Ocular Services on Demand, Madison, Wisconsin, United States
  • Paul E Miller
    Ocular Services on Demand, Madison, Wisconsin, United States
  • Helen Booler
    Pathology, Roche Innovation Centre Basel, Basel, Switzerland
  • Melissa Schutten
    Genentech Inc, South San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Vladimir Bantseev, Genentech, Inc (E); Sara Parker, Genentech, Inc (E); Roxanne Andaya, Genentech, Inc (E); Chris Schuetz, Genentech, Inc (E); Brian Christian, None; Paul Miller, None; Helen Booler, Roche (E); Melissa Schutten, Genentech, Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 201. doi:
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      Vladimir Bantseev, Sara Parker, Roxanne Andaya, Chris Schuetz, Brian Christian, Paul E Miller, Helen Booler, Melissa Schutten; Determination of a No Observed Effect Level (NOEL) for Beta Glucans following a Single Intravitreal Administration to Female Dutch Belted Rabbits. Invest. Ophthalmol. Vis. Sci. 2021;62(8):201.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Beta glucans are common contaminants in the manufacturing of biopharmaceuticals. The effects of beta glucans on the eye are not well characterized, but the level of beta glucans in intravitreal ophthalmic formulation of biologics are an important consideration in both manufacturing and safety testing. This 8-day study aimed to characterize the in-life and histopathological changes following intravitreal (ITV) administration of beta glucans and determine a no observed effect level in rabbit eyes.

Methods : Female Dutch Belted rabbits were treated with a single ITV beta glucans dose (derived and concentrated from sugars in a vehicle formulation) at nominal concentrations ranging from 10 to 1000 pg/eye. Concentrations of beta glucans dosages were measured pre and post-dosing using a Factor G based assay, and measured actual post dose values were reported as the administered dosage for each portion of the study. A non-terminal, unilateral dose range finding (DRF) portion of this study established 10 to 1000 pg/eye to be well tolerated and provided a range to be confirmed in a larger bilateral definitive study with six treated groups (N=4 animals per group) including a vehicle control. Overall animals were monitored for up to 1-week post-treatment via clinical ophthalmic examination using the modified standardization of uveitis nomenclature (SUN) Working Group Grading Scheme to score aqueous/vitreous cell and flare/haze. At the end of the definitive study animals were necropsied and eyes processed for histopathologic evaluation.

Results : No beta glucan-related findings were identified in treated animals compared to vehicle control. Single dose ITV injection of beta glucan was well tolerated in-life in the DRF portion of the study up to the maximum dose tested of 1,000 pg/eye. Doses up to 800 pg/eye (maximum dose in the definitive part) was well tolerated both in-life and on histopathologic examination. Nominal administered values were up to 1,000 pg/eye for both study portions, however samples used in the definitive study were measured post dose to be 800 pg/eye.

Conclusions : Single dose ITV beta glucans, isolated and concentrated from sugars, in a vehicle formulation did not elicit an inflammatory response or resulted in histopathologic changes. Thus, the no observed effect level (NOEL) over 8-days in rabbits was 800 pg/eye.

This is a 2021 ARVO Annual Meeting abstract.

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