Latest developments in HEPA/ULPA filters In situ leak testing

Latest developments in HEPA/ULPA filters
In situ leak testing
J.M. Vanhée, Product Manager Clean Process
Camfil Farr France
Latest developments in HEPA/ULPA filters In situ leak
testing
•• Filter
FilterControl
Control::EN1822
EN1822 vs
vsISO
ISO--EN
EN14644-3
14644-3,,”Bleed
”Bleed
Trough”
Trough”issue
issue
•• Terminal
TerminalDiffuser
DiffuserImprovement
Improvementto
toprevent
preventleaks
leaksand
and
facilitate
facilitateterminal
terminalfilter
filtercontrols
controls(PHARMASEAL)
(PHARMASEAL)
•• High
HighTemperature
TemperatureHEPA
HEPAfilter
filterimprovement
improvementto
toavoid
avoid
leaks
leaksdue
dueto
toexpansion
expansion
-1-
MPPS (Most Penetrating Particle Size)
Filter Efficiency (%)
44effects
effects
combined
combined
Total
Total
Efficiency
Efficiency
Minimum Eff.
MPPS
Diffusion
Interception
Sifting +inertia
10nm
1 µm
0,1µm
0,2µm
10 µm
Particle diameter
Particle > MPPS . . . is stopped more efficiently
Particle < MPPS . . . ALSO ! ! !
Filter Efficiency Measurement depends on Challenge Test Aerosol
PARTICLE SIZE
MPPS 0,1 < Ø < 0,2 µm
EN1822
DOP Ø = 0.3 µm
MIL STD 209
NaCl = cube 0,35 µm
EUROVENT
ISO EN 14644-3
-2-
Ø = 0.5 - 0.7 µm
EN1822 Classification
• MPPS based (0.1- 0.2µm)
• HEPA/ULPA panel filter scanning on automatic
and reliable test rig,factory made by producer
• Leak level linked to filter class
probe
filter
ISO-EN 14644-3
“B.6 Installed filter system leakage test
• confirm filter system is properly installed
and that leaks have not developed during use
• absence of leakage,
• introducing an aerosol challenge upstream of the filters and scanning
immediately downstream of the filters and support frame.
• leak test complete filter installation : filter media, frame, gasket and grid
system.”
“The installed filter system leak test should not be confused with the efficiency
test of individual filters at the place of manufacture”.
portions of ISO-EN 14644-3 are adapted from IEST-RP-CC034
-3-
ISO-EN 14644-3
B.6.2 Procedures for installed filter system leakage scan test with an aerosol
photometer
• Challenge Aerosol features
– Size
0,5 μm to 0,7 μm (geometric standard deviation
of up to 1,7)
– Concentration
• 10 mg/m3 and 100 mg/m3
• recommended > 20mgm3 and < 80 mg/m3
B.6.2.7 Acceptance criteria
Designated leaks = reading greater than 10−4 (0,01 %) of the upstream challenge
aerosol concentration.
Alternative acceptance criteria may be agreed between the customer and the supplier.
Installed filter system leakage test ... In real life
• In some cases, GOOD FILTERS according to EN1822 fail the
in situ <0.01% leak test !
• It is the so called “Bleed Through” issue
• Can be due to :
– Operating errors
• induction effects, pollution, bad 100% sampling ...
– Airflow velocity
– Challenge aerosol size
-4-
Filter « BLEED-THROUGH » Over-Velocity
HEPA/ULPA Panel Filter standard nominal front velocity = 0,45m/s
Used velocity > 0,45m/s ... 0,9 to 1 m/s => Ì efficiency
Example
H13
H14
To avoid “Bleed Trough” due to over front velocities
• Specify “High Airflow” HEPA/ULPA panel filters that are
EN 1822 tested at high airflow
ex. standard 610x610 mm MD = 600m3/h
high airflow series MD= or MG=2000m3/h
-5-
What is the actual size of aerosols used for In-Situ leak controls ?
• Photometer can’t measure particle sizes
?
Analysis of Aerosol generators currently used
• Camfil Farr Laboratories have made the measurement of aerosol produced by 2
currently used thermal aerosol generators with 3 types of oils.
CONCLUSION : Mean mass diameter is close to 0.25µm, instead of 0.5-0.7 µm
-6-
“Bleed Though” due to in-situ Challenge Aerosol size
MPPS leak rate
(EN 1822)
• As on site particle size is too small, a “leak free” filter can be considered
wrongly failing on site
Conclusion
• SITUATION
On site controls are most of the time stronger than ISO-EN 14644-3 requirement :
This is due to the use of thermal generators that generate challenge aerosol
between 0.2-0.3µm (close to MPPS) instead of 0.5-0.7µm
Consequently as acceptance criteria is 0.01% , In situ Problems can occur with :
H13 : leak rate < 0.25% @ MPPS according EN1822
H14 : leak rate < 0.025% @ MPPS according EN1822
• TO AVOID THIS PROBLEM
– Camfil Farr guaranties H14 MEGALAM leak rate < 0.01% @ MPPS instead of
standard 0.025%
– Specify U15 filters (standard leak rate < 0.0025% << 0.01%)
-7-
Latest developments in HEPA/ULPA filters In situ leak
testing
• Filter Control : EN1822 vs ISO - EN 14644-3 , ”Bleed
Trough” issue
• Terminal Diffuser Improvement to prevent leaks and
facilitate terminal filter controls (PHARMASEAL)
• High Temperature HEPA filter improvement to avoid
leaks due to expansion (TERMIKFIL)
PHARMASEAL
An innovative solution for ducted ceiling terminal HEPA/ULPA filtration
For Pharmaceutical Industry and Biotechnology facilities
1 - Design : ZERO leak policy
2 - Full filter control equipped
3 - Individual Isolation possibility
-8-
PHARMASEAL
A solution that has already proved itself
Examples of recent projects
Amgen
Amgen
Idec
Wyeth BioPharma
Bayer
Lilly
Merck
Berlix *Schering
Cangene
Wyeth
Puerto Rico
Rhode Island
California
Missouri
California
Indianapolis
North Carolina
Oregon
Canada
PR & Ireland
700
600
600
90
290
300
200
250
90
180
PHARMASEAL
“ZERO Leak” policy : by design
• More security
“fixed” interfaces
=> fully continuous welded
inlet collar
hood
“mobile” interfaces
=> gel seal
filter
bubble tight damper
-9-
PHARMASEAL
“ZERO leak” policy : by factory control + tracability
“Zero leak” proof by facts :
each PHARMASEAL is
leak tested under
pressure at 750Pa
Unique Serial Numbers are
assigned to each hood after
leak testing and provide
traceability.
PHARMASEAL
Fully equipped for GMP Tests (EMERY test, pressure drop, airflow, velocity)
(1) Control ports immediate access
=> hinged grille
=> captive 1/4 turn fastener
(1)
(2) Everything managed from room side
=> dedicated control panel
=> tests ports
=> filter clamping
=> damper adjustment
(2)
- 10-
(1)
PHARMASEAL
Fully Equipped for Filter GMP controls
•
•
•
•
All centralised on a ergonomic device
=> Injection + control from room side => Only 1 single person can test filter
Quick and airtight connection
=> stainless steel quick disconnect ports (1) (2)
EMERY test really performed in compliance with rules
=> aerosol dispersion ring (3)
NO EMERY IN HVAC DUCTING => Fire safety
Aerosol Input (2)
100%(1)
Diffusion ring(3)
(2)
PHARMASEAL
Easy and Secured filter installation and replacement
No clamping effort nor complexity => pre-positioned retaining rotating tables (1)
Immediate perfect filter positioning => filter guides as standard (2)
No leak nor by-pass risks => gel seal / knife edge sealing technology (3)
(2)
(3)
(1)
- 11-
PHARMASEAL
Individual Isolation Possibility Bubble Tight Damper
Visible and precise adjustment from room side
Full balancing capabilities
Airtight individual isolation
Camfil Farr “bubble tight” damper
knife edge
damper position indicator
gel
PHARMASEAL
Individual Isolation Possibility Bubble Tight Damper
ADVANTAGES
• Filter Maintenance
• diffuser isolated
=> no non filtered air supplied into the room during filter
maintenance
=> no contamination
=> no need heavy room decon procedure
• can be done without stopping HVAC
• Local filter decontamination
• with decon shroud
• Room decontamination
Reduces Downtime & Expenses
- 12-
Camfil Farr “bubble tight”
damper
PHARMASEAL
A Bio-Pharma GMP designed
11
22
33
44
55
General
Immediate access to filter and all controls from roomside => hinged grille
Filter installation and replacement
No clamping effort nor complexity => pre-positioned retaining rotating tables
Immediate perfect filter positioning => filter guides as standard
No leak nor by-pass risks => gel seal / knife edge sealing technology
Filter GMP controls
All centralised on a ergonomic device => integrated side control panel
Quick and airtight connection => stainless steel quick disconnect ports
EMERY test really performed in compliance with rules => aerosol dispersion ring
Individual airflow adjustment
Visible and precise adjustment from room side => damper position indicator
Full balancing capabilities => guillotine damper
Full balancing and airtight module isolation => Camfil Farr “bubble tight” damper
QA evidences
Full traceability items included => unique serial number, individual leak test,
Latest developments in HEPA/ULPA filters In situ leak
testing
• Filter Control : EN1822 vs ISO - EN 14644-3 , ”Bleed
Trough” issue
• Terminal Diffuser Improvement to prevent leaks and
facilitate terminal filter controls (PHARMASEAL)
• High Temperature HEPA filter improvement to avoid
leaks due to expansion (TERMIKFIL)
- 13-
End User’s needs
High Temperature : What does it mean ?
• 350°C => Sterilization & Depyrogenation tunnels
(destroy endotoxins)
• 230°C - 250°C => Sterilization & Depyrogenation static ovens
• 120°C => Granulation dryers
• < 70°C - 80°C => HVAC
End User’s needs :
FDA / EUGMP Requirements
Sterile Products
•EU / GMP :
Class A = ISO5 operational => HEPA filtration
•FDA Guidelines
Guidance for Industry Sterile Drug Products Produced by Aseptic Processing—
Current Good Manufacturing Practice September 2004
Class 100 (ISO5)
Overall Efficiency > 99.97% 0.3µm
Leak -free @ 0.01% with scanning of the filter face + frame
HT FILTERS ARE SCANNED BY BIO-PHARMA CUSTOMERS
- 14-
En User’s needs :
Where in its process ?
• Static Ovens : 250°C
FRSi
SOFILAIR HT230
HT HEPA Filters
End User’s needs :
Where in his process ?
Entry zone
Hot zone
Cool zone
• Tunnels : 350°C
Process
Vials entry (HEPA
Filtered zone)
Process
HT HEPA
Fiers
ess
Proc
Vials washing
Vials Heating 350°C
(sterilization +
depyrogenation)
- 15-
Vials Zone @ 350°
AIR
High Temperature : HEPA Filters requirements
• => components high temperature resistant <=> no degradation
• => filter assembling high temperature resistant <=> expansion
• => no particle shedding (out gassing) <=> “burning” cycle
Filter Components
5 Main Components
Frame
Media
Sealant
t
ra
pa
Se
Gasket
or
- 16-
High Temperature : What does that means for filters ?
TEMP
Sealant
Gasket
LUT
JOINT
350°C Ceram. Glass
Fibre
230°C / Silicon Silicon
250°C
120°C
PU
< 70°C / PU
80°C
PU/
EPDM
PU /
EPDM
Frame
CADRE
SS
Ceram.
SS
Separ.
SEPAR.
Alum
Glass
Glass
Alum
Media FILTRE
Filter
MEDIA
GF-HT FRK, F-Series
TERMIKFIL
GF-HT SOFILAIR-HT230
FRSi, K-Series
Metal
Glass
Alum
GF
Metal
Plastic...
Hot Melt
GF
SOFILAIR-HT120
Absolute
SOFILAIR(80°C)
Close Pleat
MEGALAM
350-400°C CF Solutions Efficiency : Camfil Farr Guarantee
FRK
TERMIKFIL
• Prior to any Heating
Factory certified
H13 @ 20°C New
> 99,95% MPPS
Leak-Free : YES
• After Factory Heating
(300°C)
Factory certified
> 99,99% 0.3µm
Leak-Free : YES
• After initial on-site
burn-in cycle
99.97% 0.3µm overall
Leak-free : NO
• After initial on-site burnin cycle
99.99% 0.3µm overall
Leak-free : YES
- 17-
350°C HEPA Filtration : main problem / Leak-free : NO
• Torsional forces (expansion)
=> cracks between sealant and frame => leaks
Differential expansions : sealant cracking => leak frame/sealant
• Palliative Solution
Spacers
“dynamic seal” BOSCH
(Bausch+Ströbel, IMA,...)
+
FRK
+
- 18-
Differential expansions : sealant cracking => leak frame/sealant
• Preventive Solution
a high temp. consistent set
Frame + Sealant + Media
=> TERMIKFIL
ceramic frame
glass fibre media
ceramic sealant
Latest developments in HEPA/ULPA filters
In situ leak testing
THANK YOU
ANY QUESTIONS ?
J.M. Vanhée, Product Manager Clean Process
Camfil Farr France
- 19-