8 ^{Analytics and virus}

production processes

Emma Petiot

3d.FAB, Univ Lyon, Université Lyon1, CNRS, INSA, CPE-Lyon,

ICBMS, UMR 5246, 43, Bd du 11 Novembre Villeurbanne

cedex, France

CONTENTS

8.1 Introduction: Regulatory Context for Analytics Development...................201

8.2 Analysis of Viral Products...........................................................................202

8.2.1 Biological Attributes of Virus-Based Products...............................202

8.2.2 Implications of Process Phase on Analytics Choices .....................203

8.3 Viral Quantification Methods.......................................................................205

8.3.1 Infectious Particle Quantification.....................................................205

8.3.2 Total Viral Particles Quantification.................................................208

8.3.2.1 Immuno-Based Assay........................................................213

8.3.2.2 Particle Counters................................................................215

8.4 Process Analytical Technologies and in-Line Analytics for Viral Production

Processes.......................................................................................................217

8.4.1 Off-line, At-line, On-line, and In-line Definitions..........................218

8.4.2 Process Analytical Technology for Viral Production Processes ....218

References..............................................................................................................220

8.1

INTRODUCTION: REGULATORY CONTEXT FOR ANALYTICS

DEVELOPMENT

For pharmaceutical products and especially viral vaccines, clear guidelines are issued

by regulatory agencies (FDA, EMEA) to release production lots. This means that the

analytical tools allowing for production lot characterization and validation also must

be approved and validated upfront. This is to be considered while implementing a new

analytical test for a process or replacing an “old-fashioned” analytical assay.

Developing new analytical methods used in pharmaceutical production processes is

managed through different methodologies described for example in the FDA gui-

dance [1]. Ultimately, such quantification or detection methods must be validated. If

the process is implemented in GMP facilities, fully validated methods are required

with an extensive evaluation of the precision and robustness of each assay. Changes in

the process (such as different matrix) need to be assessed as well as how these

changes will affect the assay. The documentation to be submitted to the regulatory

agencies must include a full validation protocol and extensive report. As described

DOI: 10.1201/9781003229797-8

201