Filter Validation Training-By PALL

Validation Services
Seminar
Morven McAlister & Vanessa
Merefield
SLS Life Sciences Training

May 12, 2006
Presentation Outline
Overview of validation tests
Parametric Approach
Selection of worst case test
parameters
Product bracketing
Additional Validation tests
Trends / Issues
© Pall Corporation 2006

Pall Validation Sites
Validation Laboratory
Validation Definition
“…establishing documented evidence

which provides a high degree of
assurance that a specific process will
consistently produce a product
meeting its predetermined
specifications and quality attributes.”
FDA Guideline on General Principles of Process Validation, 1987

Need for Validation (1)
“ Filtration is a common method of sterilizing

drug product solutions.”
FDA Guidance for Industry Sterile Drug Products Produced by Aseptic Processing
– Current Good Manufacturing Practice (2004)
Chapter IX – Validation of Aseptic Processing and Sterilization
“ For sterile products, the validation of
sterilising processes should be of the same
standard as for products authorised for
marketing”
European Guide to Good Manufacturing Practices (1998)
Annex 13 - Manufacture of investigational medicinal products

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… have
havetoto …
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maynotnotoften
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Global Consequences
Growth through mergers and consolidation:
Can larger companies react swiftly enough
to changes?
Higher complexity and costs of clinical
trials: Delay in bringing new compounds to
market
“…in the last four years (2000-2003) the US FDA on
average has approved 22 new molecular entities (NME)
per year compared to an average annual approval rate of
39 NMEs in the four prior years”
Leslie Platt, Ernst & Young
“It is particularly critical to validate the
efficacy of the (sterilizing) filtration process.
“…ensure that worst-case formulation and
processing parameters are adequately
studied, evaluated and documented.”
“This data should be available during current
drug pre-approval inspections and for already
marketed products produced by sterile
filtration.”
FDA Human Drug CGMP Notes (1995)
Filter Validation Testing - Overview
Bacterial Viability
Establishes bactericidal properties
Determines suitable flush protocols
Bacterial Retention
Confirms sterilizing capability of process
membrane under worst case conditions
Compatibility
Confirms maintenance of filter integrity after
exposure to worst case fluid and process

Filter Validation Testing - Overview
Extractables
Provides quantitative and qualitative analyses of
filter extractables in model solvent
Product-specific integrity test values (ITV)
Establishes filter integrity test values for process
filtration assembly wet with process fluid
Adsorption Testing
Determines extent of adsorption of product
components following filtration of product

Product Information Sheet (PINS) /
Process and Product Questionnaire
(PPQ)

PINS / PPQ
Overview of customer’s fluid & process parameters
Used to establish fluid / process-specific test
protocols representing worst case test conditions
All information needed to complete full validation
package
Requires exact concentration (%) of each
component and carrier solvent in fluid
Used in determining model solvent for extractables
test
Allows determination of potential testing issues,
e.g.
– Bactericidal properties, Compatibility issues
Execution of Validation Package (US)
Customer completes Product Information Sheet
Pall writes protocols and sends to customer for approval
Customer contacts Pall project managers directly with any

questions
Customer sends following items to Pall:
-Signed/approved protocols
-Sample product / MSDS / PO
Testing commences at Pall
6-8 weeks
Pall project manager write reports
Reports reviewed and issued to customer

Product Grouping / Selection of Worst
Case Conditions

Selection of Worst-Case Conditions
for Validation Testing
“A set of conditions encompassing upper and
lower processing limits and circumstances,
including those within standard operating
procedures, which pose the greatest chance of
process or product failure when compared to
ideal conditions”
FDA Guideline on Sterile Drug Products Produced by Aseptic Processing, 1987
“Filter validation should be conducted using the

worst-case conditions, such as maximum filter
use time and pressure”
FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic
Processing – Current Good Manufacturing Practice, 2004
Parametric Validation - Aim
Determine any effect of the fluid on the filter

and on B. diminuta or suspect bioburden
isolate
Bacterial viability and retention testing
Compatibility testing
Determine any effect of the filter on the

product formulation
Extractables testing
Adsorption testing
Parametric Validation - Strategy
Product attributes
Process parameters
Scientific rationale
Worst-case conditions
Use of actual products wherever
possible

Selection of Worst Case Conditions for
Validation Testing – Product Grouping
As per 1987 Aseptic Processing Guideline,
product “families” can be grouped
“Worst case” models must be justified by scientific
rationale
Typically, highest concentration of active

under highest operating parameters (maximum
process flow rate, differential pressure,
temperature) represents “worst-case” model

Considerations for product grouping
Product components
Test fluid should represent maximum no. components
present, including active
Concentrations of components
Highest concentration of components typically tested
Consider active and other constituents

Ionic Strength
Affects surface charge of membrane and test
organism and potential adsorptive interactions
Osmolarity
High osmolarity may cause shrinking of
microorganisms
pH
Affects surface charge of membrane and test
organism and potential adsorptive interactions
Affects viability of test organism
Test extremes of pH

Viscosity
High viscosity fluids usually require higher pressure
and/or elevated temperature processing
Typically also longer filtration duration
Surface Tension (incl. surfactants)
Presence of surfactants (> 0.5%) can reduce
adsorptive capture
Nutrients
Low nutrient (oligotrophic) environments may reduce
bacterial cell size / change cell surface characteristics
Temperature
Extremes of temperature range typically tested
Bracketing of Products
Process Parameter
Active Volume Time Flow rate Pressure Temperature

concentration
0.25 mg/mL 50 L 45 mins 1.11 L/min 0.8 bar 20ºC
10mg/mL 200 L 90 mins 2.22 L/min 0.7 bar 20ºC
20mg/mL 100 L 60 mins 1.67 L/min 1.2 bar 20ºC

Grouping of Products
Parameter
Product pH Surface Viscosity Osmolarity Ionic

Tension Strength
A 5.83 73.4 1.2 277 0.153
B 6.63 72.4 1.3 233 0.164
C 5.13 71.14 8.4 150 0.083
D 6.47 71.9 1.2 249 0.171
E 5.51 72.6 8.9 138 0.080
F 5.94 71.7 9.6 281 0.177

Bacterial Viability / Flush Testing (1)
Test bacteria (~106 CFU/mL) inoculated into

customer fluid and control fluid (sterile
deionized (DI) water)
Bacterial concentration monitored in fluid and

control over process time
Fluid & process established as bactericidal,

moderately bactericidal or non-bactericidal

Test Methodology

Selection of Worst Case Conditions
for Bacterial Viability Testing
Actual product used
Viability determined over total contact time of
product with filter
Maximum process temperature (≤ ≤ 37oC)
If process temperature >37oC, approach for
moderately bactericidal products may be
required
Recirculate product at process temperature for
maximum contact time, followed by bacterial
challenge in product at ≤ 37oC

Definition of Bactericidal
Non-bactericidal
A decline in viability of less than one log (<90%)
in product over the process time
Bactericidal
A decline in viability of greater than 1 log (>90%)
within 60 minutes of exposure in product
Moderately Bactericidal
A decline in viability of less than 1 log over 60 minutes,
in conjunction with a decline in viability of 1 log or
more over the process time
May allow for an in-product challenge after product
recirculation
Residual Effects (bactericidal fluid only)
Removal of bactericidal fluid from test filter
Fluid passed through test filter then rinsed with
flush fluid (typically DI water)
Additional volume of DI water passed through
test filter disc, collected and inoculated with low
concentration of test organism
No. bacteria recovered from fluid must be within
30% of bacterial count recovered from control

Recovery Flush (non-bactericidal fluids only)
Removal of test fluid from recovery (“analysis”)
filters
Test fluid or control inoculated with a low
concentration of test bacteria
Vacuum filtered through recovery filter and flush
scheme (typically DI water) applied
No. bacteria recovered from test fluid must be
within 30% of bacterial count recovered from
control
Options for Bacterial Retention Test
Fluid Type
Non-Bactericidal Moderately Bactericidal

Bactericidal
Challenge Fluid Fluid

performed recirculated recirculated
by inoculating for process for process time
bacteria time followed followed by flush
in fluid by challenge and challenge using
directly (seeded using fluid surrogate solution
challenge) inoculated with inoculated with
test bacteria test bacteria

Microbial Challenge –
Bactericidal Fluids
“In such cases, the fluid should simulate the

product as closely as practical in terms of
viscosity and other physical characteristics
that are not antagonistic towards the
microbial challenge”

Challenge Fluid Selection for
Bactericidal Products
Product (short term) with flush
Modified product (no preservative)
Modified product (reduced or no active)
Placebo (where appropriate)
Surrogate fluid (e.g. saline lactose broth)
Similar chemical properties

Microbial Challenge
“The (challenge) microorganisms should be small
enough to both challenge the filter's nominal porosity
and simulate the smallest microorganism that may
occur in production.”
“The microorganism Brevundimonas diminuta (ATCC

19146) when properly grown, harvested and used, is a
common challenge microorganism for 0.2 µm rated
filters because of its small size (0.3 µm mean diameter)”
FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic
Processing – Current Good Manufacturing Practice, 2004

SEM of 0.2 µm Membrane *
Section View
Challenged with 5 x 108
B. diminuta cells per cm2
Osumi et al., PDA J. Pharma. Sci. &

Technol., v. 50: pp. 30-34, (1996)
20 µm
Typical membrane
thickness ~160 µm
* Pall Ultipor® Nylon 6,6 NR Grade

Criteria for Bacterial Retention Testing
of Sterilizing Grade Filters
Brevundimonas diminuta (ATCC 19146) or other
“worst-case” bioburden isolate
Controlled culture conditions (ASTM F838-05)
Minimal size (B. diminuta 0.3 x 0.8 µm)
Monodispersed
Demonstrate penetration of 0.45 µm rated
control filter
Simulate “worst-case" process conditions
Total challenge ≥ 1 x 107 CFU/cm2
Analyze total effluent for sterility
© Pall Corporation 2006 (Ref: ASTM-F838, PDA TR26)

for Bacterial Challenge Testing (1)
Operating parameters
Flow rate
Differential pressure
Filter throughput per cm2
Typically, maximum
Total challenge duration
values for each
Temperature
No. batches processed per
test parameter
filter assembly
Filter sterilization conditions

Flow rate and pressure are interdependent
Validate highest flow and highest pressure to
meet or exceed both process parameters
Hydraulic shock – pulsing can be used
B.diminuta inoculated into product wherever
possible

Test Filter
Same membrane family and pore size rating
47-mm membrane discs typically used from
standard production
Minimum production physical QC test limit
“Low KL” discs
Pall QBP (quantitative bubble point)

Bacterial Challenge
Challenge method dependent on fluid properties

Bactericidal vs. Non-Bactericidal
Bacterial retention is confirmed if no penetration

of test membrane filter occurs under test
conditions that mimic the full-scale process
conditions

Bacterial Challenge (Non-Bactericidal Fluid)
Recirculation with Seeded Challenge Solution

Product Recirculation (Bactericidal Fluid)

Bacterial Challenge (Bactericidal Fluid)
Seeded Challenge Solution

Adsorption Testing
To quantify the amount of components adsorbed
from the product onto the filter after passing
through test filters
Enables calculation of volume of product which

should be flushed through process filter to ensure
saturation of the filter
Pall collects filtrates and customer performs

analysis

Adsorption Testing
Peristaltic pump
Tubing
Test filter
disc in
housing
Filtrate sample
Product collection vials
Reservoir
for Adsorption Testing
Maximum temperature
Maximum flow rate
Small batch size

Maximum filter throughput
Maximum contact time

Compatibility Testing
Demonstrates compatibility of specific
filter with customer process fluid
Filter exposed to process fluid for

specified period under pre-determined
conditions
Compatibility determined by performing

integrity tests on filter pre- and post-fluid
exposure and visual examination of filter

for Compatibility Testing
Testing uses actual customer fluid
Filters sterilized under maximum
conditions (time/temperature) prior to
product exposure
Testing conducted at maximum
process temperature
Exposure time must be equal to
process time minimally

Extractables Testing
Potential sources:
Hardware, support layers, membranes,
wetting agents, casting additives, etc.
Solvent Additives Oligomer
Polymer
Polymer
Chain
Surface
SURFACE INTERFACE


Extractables Assessment
Filter reciprocated in Solvent transferred to

extracting solvent Rotary Evaporator
Pre-weighed
Crucible
Extractables Assessment
Non-Volatile Residue Fourier Transform Infra-red

(NVR) Spectroscopy (FTIR)
Quantity Identity

Qualitative and quantitative analyses of
extractables from process filter
Non-volatile residue (NVR)
UV-Vis, FTIR
Model solvent used based on process
fluid characteristics
Test conditions reflect process
temperature and time

Advantages of NVR/IR Model System
Wide range of models available

NVR detects all nonvolatile material
Flexible, widely applicable IR
characterization; good for unknown
identification/investigation
Self-Validating; negative and positive
controls minimize “method validation
blues”

Additional Analytical Methods
UV-Visible spectroscopy for transparent

solvents
TOC for aqueous solutions
GC-MS for volatiles/semi-volatiles
LC or LC/MS for nonvolatiles or heat-
sensitive compounds
ICP/MS (Inductively Coupled Plasma/Mass
Spectrometry) analysis for metallic
extractables, if necessary.
for Extractables Testing (1)
Model Solvent Approach
Determines contribution of filter components to fluid
effluent
Customer fluid - type and concentration of
components
Increase solubility & concentration of low MW
weight substances in fluid due to chemical attack?
Typically, components <10% volume do not exert
significant solubility/compatibility effects
Fluid pH considered independently

(Ref: Weissman)
for Extractables Testing (2)
Process Parameters
Temperature
Testing conducted at temperature equal to or
greater than process temperature
Filter duration (total contact time)
Minimum of two extraction cycles
(24 hours per cycle)
No. extractions completed is equal to or greater
than total contact time of filter with product

Product-wet Integrity Test Values
All three test are
based on the same
physics, the flow of
Gas Source
gas through a
Air, N2 Gauge liquid-wetted
Pressure membrane
Bubbles under
Regulator
Test Filter
applied pressure
Bubble Point
Forward Flow
Pressure Hold
Product-wet Integrity Test Values
Determine test parameters appropriate for

establishing integrity of a filter when wet with
customer fluid
Values determined for filter wet with customer
fluid and correlated to reference fluid-wet value
Reference fluid-wet values correlated to
bacterial retention (published in Filter
Validation Guide).

Membrane Filter Integrity Testing
Membrane filter wetted with water or product
Pressurized with air or N2 at validated pressure
Flow of air through wetted membrane measured
Atmospheric pressure
Low diffusive gas flow
through small wetted
Test Gas pores (integral membrane)
Pressure High convective gas flow
through large pores, e.g.
defective membrane areas
© Pall Corporation 2006 Liquid-wetted Membrane

Multi-point Forward Flow Curve
Flow (ml/min)
25
•
20
•
15 •
• “Bubble
Point”
10
• • Transition
5
• • • Region
• •
1 2 3 4
Pressure (bar)

KL Value Determination
Transition from diffusive flow
to open pore flow
Bulk gas
Gas Flow flow
through
Pressure open pores
Diffusive flow
(Q/P)
Pressure KL
KL is the pressure at which the two dotted lines cross
Diffusive Flow Spectrum
Flow Product wet Water wet
1 KL(P) 2 KL(W) 3
© Pall Corporation 2006 Pressure
Product Wetted Integrity Pressure
Determination of test pressure
KL in product KL in water
Product KL Curve
Gas Flow
Pressure
x
(Q/P)
Calculated Water KL Curve
Test Pressure
x
FF test pressure in water
© Pall Corporation 2006 P (mbar)

for Product-Wet Integrity Testing
Product
Surface Tension
If surface active agents present in product,
surface-tension derived test pressure used
Viscosity
Viscous products may require extended
equilibration or test dwell times
Process Parameters
Temperature

Effect of Area on “Bubble Point”
Flow (ml/min)
250
200
150
High area cartridge Low area disc
100
50
0
Pressure (psi) 40 “BP” 50 “BP” 60
Cartridge “bubble points” are typically lower than
disc
© Pall Corporation 2006 “bubble points” using the same membrane
Critical Testing Parameters
Composition
Sterilization
Throughput
Conditions
Osmolarity
Flow Rate
Viscosity
Strength
Tension
Surface
Temp
Filter
Ionic
Time
pH
∆P
Test Type
Viability
Bacterial
Challenge
Extractables
Compatibility
ITV
Adsorption
© Pall Corporation 2006 Considered for Evaluated for

“worst-case” information only
Additional Validation Testing

Kleenpak Connectors
Soiling Test
Ability of KPC to produce
sterile connection after
intentional contamination
with bacterial spores
Male & female connector
soiled with Geobacillus
stearothermophilus
Challenge level > 105 CFU
per device

Kleenpak Connectors
Model Solvent Approach
Compatibility
Tensile Strength

Disposable Systems
Tubing, bags etc
Extractables
FTIR, GCMS, UV
Bioburden
14 day incubation period
2 growth media
Endotoxin
If product shelf-life study, qualification of assay
with product required
Sensitivity 0.005 EU/mL
Pallchek
Extensive validation required
Protocols currently under developments
Various test fluids (water, buffers, media etc)
Various ATCC bacterial strains
Potential for product-specific validation
as part of Validation services

Preparation for an audit

Preparation for an Audit (1)
SLS Labs are not working to GMP
Audit Hosts
QA & SLS Lab and project managers present
SLS procedures must be available and
show documented evidence that they are
followed
Training Records
Must be updated with current SOP revisions
Evidence of competency

Validation Services – Goals / Issues

Trends in Validation Services (US)
Increase in projects from biotechnology

companies and universities
Increase in generic drugs
Increase in projects from S.America
Increase in extractables projects for pre-filters
Decrease in project turnaround times

Trends in Validation Services -EU
Customers requesting PWIT testing performed in

triplicate
Contract manufacturers requesting product
groupings
10-15% increase in filter validations / year
More interaction with filter manufacturer and
customer
Increased interest in extractables

Goals - Validation Services
PINS/PPQ
Incomplete PIN sheets frequently submitted
Customers often lack understanding of process
PM calls / visits customer to obtain full details
Illegible handwriting on PIN/PPQ
Currently PM calls for clarification
“Typeable” PINS now complete

PINS/PPQ to be submitted via Pall web site
Target Date – August 2006

During customer routine QC Product Analysis
unidentified peaks reported
Traced to Pall filter cartridges
3 recent occurrences
FDA/PDA recommend all extractables are identified
More detailed analysis required
GCMS installed in PW on May 02, 2006
IQ/OQ currently being performed by manufacturer
Training scheduled immediately after IQ/OQ
Estimated target date for use in customer work – mid

June 2006
Global team needs formed to prioritize testing needs
Globalization
Need to standardize test SOPs based on best practise
globally
Ensure data interpretation same globally
Review validation testing prices globally
Ability to easily communicate with global team
Shared resources (e.g. extractables reports)
Validation Team Room
Shared global objectives
V.Merefield (Europe), M.McAlister (W.Hemisphere),
H. Nomura (Asia)
First meeting held Jan 2006. Each group working on
action items
Shared Issues - Validation Services
Customers requesting data to support pre-filters

(API)
Compatibility & Extractables Data
SLS UK and US have performed extractables
studies for a range of pre-filters & solvents
How do we confirm compatibility?

Shared Issues - Validation Services
Test Discs
Urgent considerations:
Global sourcing of 47-mm discs
Low spec media – both layers?
Certification of 47-mm discs
Considered a priority by global validation team
SOP written by Chris Lewis….under review
List of manufacturing sources for discs underway

Additional Questions?

Reference Documents (1)
1. Bowman, F., M.P. Calhoun and M. White, “Microbiological methods for quality control of
membrane filters”, J. Pharm. Sci., v. 55; p. 818 (1967)
2. Pall, D.B., “Quality Control of Absolute Bacteria Removal Filters,” Bull. Parenteral Drug
Assoc., 29, 392-204 (1975).
3. Howard, G. and R. Duberstein. “A case of penetration of 0.2 µm rated membrane filters by
bacteria.” Journal of the Parenteral Drug Association., v. 34; p. 95 (1980)
4. HIMA (now AdvaMed), “Microbiological Evaluation of Filters for Sterilizing Liquids,” draft
doc. No.3 Vol. 4, April, 1982 (obsolete)
5. ASTM, “Standard Test Method for Determining Bacterial Retention of Membrane Filters
Utilized for Liquid Filtration,” Standard No. F838-83 (1983, No. F838-05, rev. 2005)
6. FDA Guideline on Sterile Drug Products Produced by Aseptic Processing, 1987
7. FDA CDER Perspective on Isolator Technology, ISPE Barrier Technology Conference,
Dec. 1995
8. FDA Guidance for Industry for the Submission Documentation for Sterilization Process
Validation in Applications for Human and Veterinary Drug Products, 1994
9. FDA Human Drug CGMP Notes, Dec. 1995
10. PDA Technical Report No. 26, “Sterilizing Filtration of Liquids,” PDA J. Pharmaceutical
Science and Technology, 52 (3) Supplement, 1-31, 1998

Reference Documents (2)
11. FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic Processing –
current Good Manufacturing Practice, 2004
12. Weitzmann, C. The use of model solvents for evaluating extractables from filters used to
process pharmaceutical products, Pharmaceutical Technology, 21 (#4), 72-99 (1997)
13. Pall Corp., “Determination of product wet integrity test values for Pall filter cartridge,” Publ.
No. USTR 1471(1)
14. Sundaram, S. et al., Considerations in Using "Bubble Point" Type Tests as Filter Integrity
Tests, Part I: Effect of Test Methodology on Filter Cartridge “Bubble Point” Measurements
and Implications for the Use of “Bubble Point” Type Tests as Correlated Tests,
Pharmaceutical Technology, Sept., 2000
15. Sundaram, S. et al., “Considerations in Using "Bubble Point" Type Tests as Filter Integrity
Tests, Part II: Effect of Filter Area on “Bubble Point” Measurements and Implications for the
Use of “Bubble Point” Type Tests as Correlated Tests,” Pharmaceutical Technology, Oct.,
2000
16. Pall Corp., “Validation Guide for Pall 0.2 micron Ultipor N66 and N66 Posidyne Membrane
Cartridges,” (1980)
17. USP General Information Chapter <1227>, Validation of Microbial Recovery from
Pharmacopeial Articles, USP 27, USPC, Inc., Rockville, MD, 2004, p. 2625
18. Osumi, M., N. Yamada and M. Toya, “Bacterial retention mechanisms of membrane filters,”
PDA Journal of Pharmaceutical Science and Technology, v. 50; pp. 30-34, (1996)
Thank you for your
attention!

Filter Validation Training-By PALL

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Validation Services

SLS Life Sciences Training

© Pall Corporation 2006

“…establishing documented evidence

FDA Guideline on General Principles of Process Validation, 1987

© Pall Corporation 2006

“ Filtration is a common method of sterilizing

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

Pall writes protocols and sends to customer for approval

Customer contacts Pall project managers directly with any

Customer sends following items to Pall:

Testing commences at Pall

Reports reviewed and issued to customer

© Pall Corporation 2006

“Filter validation should be conducted using the

Determine any effect of the fluid on the filter

Determine any effect of the filter on the

© Pall Corporation 2006

Typically, highest concentration of active

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

Active Volume Time Flow rate Pressure Temperature

0.5 mg/mL 50 L 45 mins 1.11 L/min 0.8 bar 20ºC

1.0 mg/mL 100 L 60 mins 1.67 L/min 1.2 bar 20ºC

10mg/mL 200 L 90 mins 2.22 L/min 0.7 bar 20ºC

20mg/mL 100 L 60 mins 1.67 L/min 1.2 bar 20ºC

© Pall Corporation 2006

Product pH Surface Viscosity Osmolarity Ionic

A 5.83 73.4 1.2 277 0.153

B 6.63 72.4 1.3 233 0.164

C 5.13 71.14 8.4 150 0.083

D 6.47 71.9 1.2 249 0.171

E 5.51 72.6 8.9 138 0.080

F 5.94 71.7 9.6 281 0.177

© Pall Corporation 2006

Test bacteria (~106 CFU/mL) inoculated into

Bacterial concentration monitored in fluid and

Fluid & process established as bactericidal,

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

Non-Bactericidal Moderately Bactericidal

Challenge Fluid Fluid

© Pall Corporation 2006

“In such cases, the fluid should simulate the

FDA Guideline on Sterile Drug Products Produced by Aseptic Processing, 1987

© Pall Corporation 2006

© Pall Corporation 2006

“The microorganism Brevundimonas diminuta (ATCC

© Pall Corporation 2006

Osumi et al., PDA J. Pharma. Sci. &

* Pall Ultipor® Nylon 6,6 NR Grade

© Pall Corporation 2006 (Ref: ASTM-F838, PDA TR26)

© Pall Corporation 2006

© Pall Corporation 2006

© Pall Corporation 2006

Challenge method dependent on fluid properties