Rapid Manufacture and Release of a GMP Batch of Zaire Ebolavirus Glycoprotein Vaccine Made Using Recombinant Baculovirus-Sf9 Insect Cell Culture Technology

F or the ongoing 2014 Ebola virus outbreak, all viable options and technologies need to be evaluated as potential countermeasures to address this emerging biological threat. Novavax, Inc. has a rapid, practical vaccine development and manufacturing platform with the capability to deliver clinical trial material and, ultimately, commercial doses in response to novel infectious disease agents.[1-3] This report describes the application of our platform technology for the successful generation, manufacture, and release of a clinical batch of Zaire ebolavirus glycoprotein nanoparticle vaccine three months from project initiation. The key enabling factors were: • An integrated project plan and frequent cross-functional response team meetings • Forward processing of intermediates prior to completion of quality control testing • Rapid development and confirmation of the platform process at laboratory-scale • Advanced use of the baculovirus master virus seed to bypass production of the working virus seed • Rapid analytical method development • A manufacturing process that employs single-use manufacturing technology • Collaboration and flexibility from key raw material suppliers and contracted service providers Introduction In 1976, a new virus (later designated genus Ebolavirus), which caused acute hemorrhagic fever in people of Zaire (now the Democratic Republic of Congo) was reported.[4] Since then, five ebolavirus species have been identified. The species designated Zaire ebolavirus (EBOV), Sudan ebolavirus, and Bundibugyo ebolavirus have caused multiple, major Ebola virus disease (EVD) outbreaks in Africa.[5] From 1976 to 2013, EVD is estimated to have claimed the lives of 1590 people.[6] In March 2014, the United Nations World Health Organization (WHO) was notified of a new outbreak of EVD in Guinea that had expanded to Liberia . Further outbreaks were identified in Sierra Leone (May) and Nigeria (July).[6] In August, WHO DirectorGeneral Dr. Margaret Chan declared a public health emergency of international concern, characterizing the 2014 EVD outbreak as “the largest, By TIMOTHY J. HAHN, BRIAN WEBB, JOHN KUTNEY, ED FIX, NANCY NIDEL, JAMES WONG, DANA JENDREK, CELIA BAULA, JODY LICHAA, MIKE SOWERS, YE V. LIU, JOHN HIGGINS, KWAN-HO ROH, ZHENG MENG, CYNTHIA OLIVER, ERICA SHANE, LARRY ELLINGSWORTH, SARATHI BODDAPATI, CHRISTI MCDOWELL-PATTERSON, ZIPING WEI, OLEG BORISOV, WIN CHEUNG, JINGNING LI, VICTOR GAVRILOV, KATHLEEN CALLAHAN, KARIN LÖVGREN BENGTSSON, MAGNUS SÄVENHED, MATS SJÖLUND, SUSANNA MACMILLAR, MALIN SCHENERFELT, LINDA STERTMAN, CAMILLA ANDERSSON, KATARINA RANLUND, JENNY REIMER, DENISE COURBRON, STEPHEN J. BEARMAN, VALERIE MOORE, D. NIGEL THOMAS, AMY B. FIX, LOUIS F. FRIES, GREGORY M. GLENN, and GALE E. SMITH Rapid Manufacture and Release of a GMP Batch of Zaire Ebolavirus Glycoprotein Vaccine Made Using Recombinant Baculovirus-Sf9 Insect Cell Culture Technology IMAGE: Created by microbiologist Cynthia Goldsmith, Centers for Disease Control and Prevention (CDC), this colorized transmission electron micrograph (TEM) revealed some of the ultrastructural morphology displayed by an Ebola virus virion. (http://phil.cdc.gov/phil/details.asp?pid=10816) Article Published Online: February 10, 2015