June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Preservation of Bevacizumab Anti-VEGF Bioactivity and Monomeric Structure During Processing into a Sustained Release Bevacizumab Intravitreal Depot
Author Affiliations & Notes
  • sarah guedez
    Ocular Therapeutix, Bedford, MA
  • Charles D Blizzard
    Ocular Therapeutix, Bedford, MA
  • allison wyand
    Ocular Therapeutix, Bedford, MA
  • Jennifer Wittbold
    Ocular Therapeutix, Bedford, MA
  • Rami F Elhayek
    Ocular Therapeutix, Bedford, MA
  • Andrew Vanslette
    Ocular Therapeutix, Bedford, MA
  • Peter K Jarrett
    Ocular Therapeutix, Bedford, MA
  • Arthur Driscoll
    Ocular Therapeutix, Bedford, MA
  • Amar Sawhney
    Ocular Therapeutix, Bedford, MA
  • Footnotes
    Commercial Relationships sarah guedez, Ocular Therapeutix (E); Charles Blizzard, Ocular Therapeutix (E); allison wyand, Ocular Therapeutix (E); Jennifer Wittbold, Ocular Therapeutix (E); Rami Elhayek, Ocular Therapeutix (E); Andrew Vanslette, Ocular Therapeutix (E); Peter Jarrett, Ocular Therapeutix (E); Arthur Driscoll, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1500. doi:
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      sarah guedez, Charles D Blizzard, allison wyand, Jennifer Wittbold, Rami F Elhayek, Andrew Vanslette, Peter K Jarrett, Arthur Driscoll, Amar Sawhney; Preservation of Bevacizumab Anti-VEGF Bioactivity and Monomeric Structure During Processing into a Sustained Release Bevacizumab Intravitreal Depot . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1500.

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

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To monitor the anti-VEGF bioactivity and bevacizumab monomer during processing into sustained release depots prepared for intravitreal injection in a rabbit model.


Bevacizumab was formulated as a solid dispersion for entrapment in a bioresorbable polyethylene glycol (PEG) matrix. The depot and entrapped drug was optimized for drug release rate and injectability using a fine gauge needle. The anti-VEGF bioactivity of the processed bevacizumab was assessed using an indirect bevacizumab (humanized anti-VEGF IgG1) ELISA kit available from Alpha Diagnostic International. The kit contains controls and the bioactivity is determined relative to a standard curve. The monomer content and high molecular weight species of bevacizumab was assessed by HPLC-SEC using methodology as described in the United States Pharmacopeia (final authorized version 1 dated July 25, 2014).


Incorporation of the anti-VEGF antibody into sustained release bevacizumab PEG depots suitable for intravitreal injection (as shown in Figure One) requires optimization of hydrogel depot processing to maintain bioactivity and monomeric structure. The processed bevacizumab, as shown in Table One, conserved its monomeric structure to a high degree (>95%) and any high molecular weight species formed were identified only as dimer. The bevacizumab completely maintained its anti-VEGF bioactivity as determined by an ELISA test relative to the bevacizumab standards.


The anti-VEGF bioactivity of bevacizumab and its monomeric form was conserved through processing steps that are necessary to control particle size to ease injectability of the sustained release bevacizumab PEG intravitreal depot. Dissolution of the bevacizumab in its monomeric form demonstrating full anti-VEGF bioactivity was confirmed and this is critical during manufacture of efficacious sustained release bevacizumab intravitreal depots.  



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