nm

1. Agenda
Background
Filtration mechanisms
Series filtration
Summary
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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2. Background

3. Membranes in Biopharma Processing
Bacteria
Mycoplasma
Product Conc.
Virus
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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4. Membrane Types in Biopharma Processing
Mycoplasma
Product Conc.
3. Microfiltration Membranes
2. Virus Retentive Membranes
1. Ultrafiltration Membranes
Prefiltration Protection for final filter
Virus
Bacteria
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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5. Sterilizing grade membranes
What is required for optimum performance?
• High, predictable retention  Sterility assurance
• High process flux  Speed of unit operation
• High filtration capacity  Economy
• High mechanical strength  Robustness at scale
• Ease of wetting  Ease of integrity testing
• Low extractables  No added contamination
• Chemical compatibility  Robust
Morphology
Chemistry
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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6. Filtration
mechanisms

7. How sterilizing-membrane filters work
Sterilizing-grade filter definition:
ASTM® F 838-15 is a standard method against
which all sterilizing grade membranes can be
compared
 Removal of a standard test organism
(Brevundimonas diminuta) at minimum
concentration of 107 cfu/cm2
Sterilizing-grade filters function primarily
on the basis of size exclusion
“A filter that reproducibly removes test
microorganisms from the process
stream, producing a sterile filtrate.”
PDA® Technical report N°26, 2008
fluid
flow
9

8. Throughput
Flux
Pores that prevent passage of bacteria or viruses can also become
plugged in streams containing foulants.
Observed as decline in flux (constant pressure) or increase in pressure
(constant flow) with time.
Membrane plugging (fouling)
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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9. Filtration Operating Modes
Constant Pressure Constant Flow
Models can give insight into fouling mechanisms
Theoretical basis for prediction of volume at extended durations
 Save time, process volume
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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10. Classical filter fouling models
Standard
pore constriction
Complete
pore blocking
Intermediate Cake
deposit

V Pore constriction
Pore blocking
surface
tion
ng
cept
urface
surface
ion
Physical concept
Formation of a surface
deposit
Pore blocking + surface
deposit
formation of
a surface
deposit
pore
blocking
+ surface
deposit
1 2
4
3
2
0 2
1 







V
K
J
J s
V
K i
e
J
J 

0










0
0
1
J
V
K
J
J b
1
1
0
0 

V
J
K
J
J
c
• Based on Darcy’s law
• Uniform particle size
• Uniform pore size
• Macroscopic description
P.H. Hermans and H.L. Bredee, J. Soc. Chem. Ind., 55T:1-4 (1936)
J. Hermia Trans. IChemE. 60:183-187 (1982)

R
PA
J 
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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11. Classical filter fouling model limitations
Standard
pore constriction
Complete
pore blocking
Intermediate Cake
deposit

V Pore constriction
Pore blocking
surface
tion
ng
cept
urface
surface
ion
Physical concept
Formation of a surface
deposit
Pore blocking + surface
deposit
formation of
a surface
deposit
pore
blocking
+ surface
deposit
1 2
4
3
2
0 2
1 







V
K
J
J s
V
K i
e
J
J 

0










0
0
1
J
V
K
J
J b
1
1
0
0 

V
J
K
J
J
c
Flux decay is a function
of only throughput
volume and is
independent of time
Assumes that only one
filtration mechanism is
occurring
Selection, Sizing, and Operation of Bioprocess Filtration Trains for Optimal Performance | 24.01.2019
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