Ranibizumab pre-filled syringe approved in the
`European Union: innovation to improve dose
`accuracy, reduce potential infection risk, and offer
`more efficient treatment administration
`
`
`
`Abstract
`
`Novartis Exhibit 2280.001
`Regeneron v. Novartis, IPR2021-00816
`
`FREE
`ARVO Annual Meeting Abstract  |   April 2014
`Jean-Eric Michaud; Juergen Sigg; Lina Boado; Joachim Momm; Cornelia Weber; Daniel Alete; Eva Peregi; Marie Picci
`Author Aliations & Notes
`Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1949. doi:
`Purpose
`Ready-to-use injections eliminate aseptic preparation steps, reducing potential iatrogenic eye infection risks due to
`suboptimal drug and device handling. Currently used pre-lled syringes (PFS) are unsuitable for intravitreal use as
`they are coated with a high amount of silicone (Si) oil, which over time may emulsify into the drug and upon injection
`may impact vision. The recently European Union (EU) approved ranibizumab (RBZ) PFS was specically designed for
`single-use intraocular injection and may save physicians’/patients’ time, improve dose accuracy, and help reduce eye
`infection risk
`Methods
`We describe some of the features, development process, and potential benets of the RBZ PFS
`Results
`Design features of RBZ PFS (Figure) include: (i) a Luer-lock closure system that holds the needle tightly and enables a
`choice of needle; (ii) a small syringe barrel (0.5 mL) with low void volume, an unambiguous dose mark ensuring high
`dose accuracy, and non-reactive borosilicate glass for storage stability; (iii) a latex-free non-retractable plunger
`preventing inadvertent drawing of non-sterile air and thereby minimizing sterility-related ocular adverse events; (iv)
`an optimized siliconization process; and (v) a specially designed blister packaging preventing any contamination of
`sterile outer syringe surface. The development of minimally siliconized RBZ PFS used a ‘baked silicone’ process.
`Briey, Si oil-in-water emulsion is spray coated to the barrel’s inner surface and subsequently heat-xed. Si oil
`migration into the RBZ solution was assessed using 2 orthogonal methods (inductively coupled plasma atomic
`emission spectroscopy and particulate matter analysis by microow imaging), and was found to be minimal. No
`relevant dierences in product stability between vials and syringes were observed (e.g. when assessed using cation
`exchange chromatography). The RBZ PFS is easy to hold and may increase the injection preparation eciency by
`saving clinicians’ time, compared to conventional vial use
`Conclusions
`

`

`Novartis Exhibit 2280.002
`Regeneron v. Novartis, IPR2021-00816
`
`The RBZ PFS aims to improve overall eciency of RBZ administration in clinical practice by potentially oering
`improved dose accuracy, a reduced risk of eye infection, and time savings for physicians and patients. RBZ PFS was
`approved for use in the EU in October 2013
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`Ranibizumab pre-lled syringe
`Keywords: 465 clinical (human) or epidemiologic studies: systems/equipment/techniques • 688 retina  
`© 2014, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to
`republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Oce prior
`to publication.
`