July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Re-packaging bevacizumab in 2-mL glass vials for prolonged sterility, stability and bio-activity
Author Affiliations & Notes
  • Jan S Peterson
    Emmes Corp, Rockville, Maryland, United States
  • Kenneth Rockwell
    Investigational Drug Service, Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Paul C VanVeldhuisen
    Emmes Corp, Rockville, Maryland, United States
  • Michael S Ip
    Doheny Eye Institute, University of California-Los Angeles, Los Angeles, California, United States
  • Ingrid U Scott
    Department of Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania, United States
  • Barbara A Blodi
    Fundus Photograph Reading Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Jan Peterson, None; Kenneth Rockwell, None; Paul VanVeldhuisen, None; Michael Ip, Genentech (C); Ingrid Scott, None; Barbara Blodi, None
  • Footnotes
    Support  NIH Grant U10EY023529
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 213. doi:
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    • Get Citation

      Jan S Peterson, Kenneth Rockwell, Paul C VanVeldhuisen, Michael S Ip, Ingrid U Scott, Barbara A Blodi; Re-packaging bevacizumab in 2-mL glass vials for prolonged sterility, stability and bio-activity. Invest. Ophthalmol. Vis. Sci. 2018;59(9):213.

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

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Abstract

Purpose : Re-packaged bevacizumab in pre-filled plastic syringes for intravitreal injection is available but with reported shelf-life limited to 60-90 days. To reduce costs for the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), bevacizumab was re-packaged in 2-mL sterile glass vials and tested to verify sterility, stability and anti-VEGF bio-activity for up to 21 months.

Methods : Three lots of bevacizumab (AVASTIN®) were re-packaged into 2-mL sterile glass vials to deliver 0.05 mL (1.25 mg) doses for clinical study use. Re-packaging was performed in a Class 100 (ISO 5) glovebox isolator following standard procedures. Stability-indicating quality tests before release of each lot included sterility (BACTEC™ and USP <71> methods), concentration and purity (by HPLC), endotoxins (Endosafe®-PTS™) and visible particulates (USP <790>). Quality tests were repeated under a stability protocol at 1, 3, 6, 12, and, for two lots, 20 and 21 months after re-packaging. All re-packaged vials were stored and shipped at 2-8°C prior to study use or quality tests. Anti-VEGF bio-activity was tested at 21 months for one lot using a GloResponse™ VEGF-A neutralization assay and compared to a fresh AVASTIN® control vial.

Results : Following re-packaging and quality release testing, 2,362 vials were available for use in SCORE2. Of those, 1,745 were used for intravitreal study treatments. The average time from re-packaging to treatment use was 7.1 ± 2.6 months (range 1.7 to 19.3 months). The stability-indicating quality tests repeated at 1, 3, 6 and 12 months continued to meet all release criteria. Over 140 unused vials from two lots were returned for quality testing after their expiration dates. They also passed the same release quality tests at 20 and 21 months, respectively. In addition, the VEGF-A neutralization assay performed on two vials 21 months after re-packaging showed relative potencies of 108.5% (CI95 = 96.3, 122.3) and 103.0% (CI95 = 90.4, 117.2) compared to a fresh AVASTIN® control vial.

Conclusions : Re-packaging bevacizumab into 2-mL glass vials provided a longer shelf life for SCORE2 compared to available plastic syringes, with maintenance of sterility and anti-VEGF bio-activity for up to 21 months when stored at 2-8°C. With a longer shelf life, small glass vials of re-packaged bevacizumab for intravitreal injection offers an important advantage over pre-filled plastic syringes.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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