TABLE 6.1

Parameters considered for process optimization and comparison of productivities in virus production

Name

Typical standard

deviation or

equation

Units

Input for process

optimization

Other comments

Ref.

Cell

concentration

±6–10% (Vicell,

Beckman Coulter)

cells/mL

Beckman

Coulter

HA titer

±0.15 log10 (1:20.5

dilution series)

Log10 HA

units/100 µL

Allows estimation of IAV

particle concentration and

total number of virus

particles.

Quick and easy measurement

Only meaningful as time course.

Depends on IAV strain. Different sources for

the red blood cells are used (chicken,

turkey, camels, seals), concentration not

always clearly defined.

[ 9]

TCID50

± 0.3 log10

TCID50/mL

Infectious virus titer

Time consuming assay

Only meaningful as time course, estimate for

infectious virus particles, PFU and TCID50

are not equivalent! Viral infectivity is a

critical parameter to determine MOI.

[ 10, 11]

PFU

± 0.2 log10

PFU/mL

Infectious virus titer

Time consuming assay

Only meaningful as time course, estimate for

infectious virus particles, PFU and TCID50

are not equivalent! Viral infectivity is a

critical parameter of an infectious virus.

[ 12]

SRID

± 10%

HAU/(µg/mL)

Standard assay for vaccine

release

SRID assays are used to determine potency

of inactivated virus vaccines and are

accepted by regulatory authorities

[ 13– 15]

vRNA

± 25%

vg

Viral genome copy numbers

Only meaningful as time course, estimate for

total virus particles, but not all RNA is

packed into virus particles, more sensitive

than HA assay

[ 16]

(Continued)

Process intensification

141