7 ^{Downstream processing}

of viral-based vaccines

Rita P. Fernandes and Cristina Peixoto

iBET, Instituto de Biologia Experimental e Tecnológica,

Apartado 12, 2781-901 Oeiras, Portugal

Instituto de Tecnologia Química e Biológica António Xavier,

Universidade Nova de Lisboa, Av. da República, 2780-157

Oeiras, Portugal

Piergiuseppe Nestola

Sartorius Stedim Switzerland AG, Ringstrasse,

Tagelswangen, Switzerland

CONTENTS

7.1 Introduction...................................................................................................175

7.1.1 Viral-Based Vaccines Manufacturing––Current Challenges in

Downstream Processing ...................................................................176

7.1.2 Traditional Methods for Virus Purification.....................................177

7.2 Purification Strategies for Viruses...............................................................178

7.2.1 Harvest and Clarification .................................................................179

7.2.2 Intermediate Purification––Virus Concentration and

Chromatography ...............................................................................184

7.2.3 Polishing ...........................................................................................189

7.3 Analytics Tools on Process Understanding and High Throughput Process-

Development.................................................................................................190

7.4 The Future in Purification Technology .......................................................192

7.4.1 New Facility Design.........................................................................192

7.4.2 Process Intensification......................................................................192

7.5 Concluding Remarks....................................................................................195

References..............................................................................................................195

7.1

INTRODUCTION

This chapter will explore the available downstream processing (DSP) strategies for

the purification of viral vectors, used for vaccine production, in both industry and

academia. The drivers for process design are the maximization of product recovery,

scalability, and robustness while operating in ideal conditions for maintaining

DOI: 10.1201/9781003229797-7

175