PDA TR26rev07 Update PDA Australia - Parenteral Drug Association
PDA FDA Joint Conference 09 2008
description
Transcript of PDA FDA Joint Conference 09 2008
![Page 1: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/1.jpg)
1
Connecting People, Science and Regulation ®
Filtration Interest Group
EU ANNEX 1, Paragraph 113Pre-use Integrity Testing
Minimizing or Increasing Risk ?
Maik W. Jornitz Group Vice President Sartorius Stedim NA Inc.
Connecting People, Science and Regulation ®
Filtration Interest Group
Disclaimer
Information within the presentation are discussion points and vary within processes and process requirements.
Some of the process suggestions can be found in existing processes, but do not represent copies.
All statements made are personal statement and do not represent any organization.
![Page 2: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/2.jpg)
2
Connecting People, Science and Regulation ®
Filtration Interest Group
Statement within Paragraph 113
113. The integrity of the sterilised filter should be
verified before use and should be confirmed
immediately after use by an appropriate method
such as bubble point, diffusive flow or pressure
hold.
Connecting People, Science and Regulation ®
Filtration Interest Group
Integrity Testing
• wetting of the filter with
appropriate fluid, commonly
water and fluid volumes
• atmospheric pressure on the
filtrate side
All integrity tests listed require at least:
![Page 3: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/3.jpg)
3
Connecting People, Science and Regulation ®
Filtration Interest Group
Statement within Paragraph 113
113. The integrity of the sterilised filter should be
verified before use and should be confirmed
immediately after use by an appropriate method
such as bubble point, diffusive flow or pressure
hold.
Connecting People, Science and Regulation ®
Filtration Interest Group
What Risks are involved, when not pre-use tested ?• Filter fails post-use test
if possible, reprocessing required
if filled or reprocessing not validated, batch needs to be discarded
economical burden
• Filter passes post-use test, but has been non-integral during filtration
hypothetical, personally never experienced in 100’s of tests
![Page 4: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/4.jpg)
4
Connecting People, Science and Regulation ®
Filtration Interest Group
Statement within Paragraph 113
113. The integrity of the sterilised filter should be
verified before use and should be confirmed
immediately after use by an appropriate method
such as bubble point, diffusive flow or pressure
hold.
Connecting People, Science and Regulation ®
Filtration Interest Group
Why would a filter fail after sterilization ?
• Most common reasons:
ignored filter manufacturer’s technical specifications
improper end-user training
improper sterilization process design and/or qualification
temperature
pressure
![Page 5: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/5.jpg)
5
Connecting People, Science and Regulation ®
Filtration Interest Group
How to prevent a filter fail after sterilization ?
• Common practice:
design steam sterilization according to filter manufacturer’s specification
run Process Performance Qualification and check the filter’s:
integrityintegrity test value changesappearance
Connecting People, Science and Regulation ®
Filtration Interest Group
Implication of the Word - sterilised
The filter has been sterilized by commonly either autoclaving or
in-line steam sterilization
Status: Filtrate Side is Sterile and requires to stay Sterile
Filling
![Page 6: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/6.jpg)
6
Connecting People, Science and Regulation ®
Filtration Interest Group
Implications for a Sterilized Process
Hold Vessel
Bulk
Filling
• Wetting fluid reaches thesterile filtrate side
• Wetting fluid potentiallydilutes product
• Pressure on sterile siderequires to be atmospheric
• Downstream volume requires to be large enough
• Cooling time to obtainappropriate temperature
RPN = Severity x Occurrence x Detection = 10 x 1-2 x 8-9 = 80 - 180
Connecting People, Science and Regulation ®
Filtration Interest Group
Process Design AlternativesWetting fluid flush diverted via a3-way valve into a flushvolume tank, followed by theintegrity test with the gas ventedthrough the vent filter.Pipe work to equipment stays overpressure.
Disadvantages:• Dilution if not dried• Additional integrity test• Additional preparation & set-up
Hold Vessel
Bulk
Filling
HydrophobicVent Filter(requires integrity testing)
P > Patm
Patm
Ptest > Patm
Flush Receival
![Page 7: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/7.jpg)
7
Connecting People, Science and Regulation ®
Filtration Interest Group
Process Design AlternativesWetting fluid flush diverted via a3-way valve through a hydrophilic/hydrophobic filter, followed by theintegrity test with the gas ventedthrough the h/h filter.Pipe work to equipment stays overpressure.
Disadvantages:• Dilution if not dried• Additional integrity test• Additional preparation & set-up
Hold Vessel
Bulk
FillingDrain
Hydrophilic/HydrophobicFilter(requires integrity testing)
P > Patm
Patm
Ptest > Patm
Connecting People, Science and Regulation ®
Filtration Interest Group
Process Design Alternatives
Redundant filtration system, whichtests filter 1. and leaves filter 2. inits sterilized form. Filter 1. will bewetted and tested via 3-way valveand drain.
Disadvantages:• Dilution if not dried• Additional preparation & set-up• Additional hold-up volume
Hold Vessel
Bulk
Filling
Drain
P > Patm
Patm
Ptest > Patm
![Page 8: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/8.jpg)
8
Connecting People, Science and Regulation ®
Filtration Interest Group
Process Design AlternativesProduct is the wetting fluid
and flushed into the equipment side.
After wetting the 3-way valve is
opened to the vent filter, followed
by the integrity test with the gas
vented through the vent filter.
Disadvantages:• Potential product loss when failed• Additional integrity test• Equipment side under Patm
Hold Vessel
Bulk
FillingDrain
HydrophobicFilter(requires integrity testing)
Patm
Patm
Connecting People, Science and Regulation ®
Filtration Interest Group
Statement Clarification Need113. The integrity of the sterilised filter should be
verified before use and should be confirmed
immediately after use by an appropriate method
such as bubble point, diffusive flow or pressure
hold.
The question to post is:Does “should” here has the same meaning as described in Q8 or Q9 ?“The use of the word should in Agency guidances means that something is suggested or recommended, but not required.”
![Page 9: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/9.jpg)
9
Connecting People, Science and Regulation ®
Filtration Interest Group
ANNEX 1. Wording Alternative
113. The integrity of the sterilising filter may be
verified before use and should be confirmed
immediately after use by an appropriate method
such as bubble point, diffusive flow or pressure
hold.
Leave the Decision to the End-User
Connecting People, Science and Regulation ®
Filtration Interest Group
Why leave it to the End-User ?
Because a post-sterilization, pre-use integrity test would not increase process safety (RPN ~ 80-180 vs. 30-60).
It is mainly an economical decision to be made.
And when steam sterilization and filtration processes are properly qualified, the filters are not adversely affected by such and users trained the risk of a failure is minimal (never non-existing).
![Page 10: PDA FDA Joint Conference 09 2008](https://reader030.fdocuments.in/reader030/viewer/2022020306/556dc944d8b42a78768b47c1/html5/thumbnails/10.jpg)
10
Connecting People, Science and Regulation ®
Filtration Interest Group
Thank you !