Filter validation

Good Manufacturing Practice�For LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.

1. 1Mr. Sagar Kishor Savale
Mr. Sagar Kishor Savale
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Mr. SagK.igshosvlSaKSe.ge
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Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale
[Department of Pharmaceutics][Department of Pharmaceutics]
[email protected]@gmail.com
2015-20162015-2016

2. Why Validate?
What needs to be Validate?
Who is responsible for Validation
Elements of validation study

Conclusion
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3. Good Manufacturing Practice
For LVP,SVP, ophthalmic veterinary medicine,
bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility &
product consistency with in known limits
Provides license to do business.
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4. Before any work is initiated to validate a filter
prerequist must be satisfied
The filter itself must be consistent &
reproducible from lot to lot
The Drug Product must be consistent &
reproducible from lot to lot
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5. Drug Manufacturer is responsible
Drug Manufacturer should select a filter
manufacturer who Provide sufficient
information and services to facilitate the
Validation
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6. Reproducibility
Sterlization
Operating Condition
Particulates
Fibers
Microbial Retention
Filter Inertness
Drug Product stability
Endotoxin
Toxicity
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7. Applies to both Drug Product & Filter
Drug Product
Chemical attributes of a drug Product should be Known & Control
within define Limits
Changing any of these attribute limit may affect not only Process
characteristic but could also neglate previous validation work
Filter reproducibility
Filter manufacture should ensure
That all filter claim should be qualified & there is control over
filter raw material
That in process and final release is perform on a per lot basis
That certificate of Quality Assurance is available
Validation Guide are available
Filter manufacturing plant may be audited
There is policies for change control.
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8. Preferred method is Moist heat minimizes
potential source of residual chemicals.
Important consideration are time,
temprature,pressure,air & condensate removal
& total no of sterlization Cycle
Thermocouple verify that adequate temp are
achieved & biological indicator verify kill by
moist heat.
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9. Step I
Obtain all relevant performance specification of filter and filter housing
StepII
Install the filter and filter housing to ensure that self drain of air and
condensate
StepIII
Perform heat distriution studies using thermocouple and biological Indicator
Both are placed upstream and downstream
StepIV
Perform on going monitoring of the sterlization for temprature and
Pressure
StepV
Ensure that ongoing operating condition are with in the filter manufacturing
defined limit
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10. Provision of the test methodology and correlation
is the responsibility of filter manufacturer and
qualification of how the test is used is the
responsibility of end user
It is not sufficient to merely put the procedure into
use without operator training and qualification of
test equipment
It is responsibility of filter manufacturer to
demonstrate correlation of integrity test value with
microbial retention
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11. Qualification is done whether manual or a
Automated
For Manual test it is important that operator
are properly trained and Qualified
Qualification of automated test instrument
should address instrumental calibration ,
verification f test accuracy and reproducibility
and verification of alarm and security feature
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12. Time
Long processing time could allow bacteria to die thereby resulting in
increased Endotoxin level
Long processing time may increased the probability for bacteria to
penetrate the filter
Temperature
Operating temp should be carefully reviewed
This be studied in terms of time at specified temp
Filter component may oxidize to varying degree of elevated temp
Pressure
The inlet pressure must be monitored
The pressure across the membrane comply with filter manufacturer
recommended limit
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13. Mobile randomly sourced extraneous substance other than
gas bubble that cannot be Quantified by chemical analysis
due to small amount of material that is present and to its
heterogeneous composition
For LVP(according to USP)
Not more than 3 particulates per milliliter larger than 10 µm
Not more than 25 particulates per milliliter larger than 25µm
For SVP
Not more than 6000 particulates per container larger than
10µm
Not more than 600 particulates per container larger than
25µm
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14. Fibers
Any Particulate contaminant with a length at least three greater than
its width
Non Fibers
Any filter which after any appropriate pretreatment such as washing
or flushing will not release fiber into the component of drug product
German Federal Health office Give standard for asbestos particulate
Fiber exceeding 2.5 µm must be eliminated
Fiber between 1 and 2.5 µm may only found in low concentration
Fiber not longer than 1 µm are of no concern
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15. To ensure that the filter is not undergoing
degradation,deformation,or some other change
To ensure that the drug product is not causing
the organism to shrink.
Sterilizing grade filter is one that when
challenged with 10
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Brevundimonas diminuta
per square centimeter of filter area will produce
a sterile effluent.
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16. The filter should be Inert
It should neither add anything to the fluid nor remove anything from
it.
Should determine by extraction and adsorption study
Various technique that have been used to measure filter inertness
Chemical Compatibility
pH and Conductivity
Oxidizable substance
Gravimetric Extractable
Weight change
Advanced analytical technique
Adsorption
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17. Drug product stability should not affected by
filtration
It affects loss of activity, lowering of activity or
conformational changes
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18. Filter does not add Endotoxin to a drug product
Endotoxin content of new filter will depend on
quality control process of filter manufacturing,
filter manufacturer and the water used in filter
manufacturing
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19. Should determine that passage of the drug
product through a filter does not cause any
toxicological effect.
All filter material of construction should be
addressed
It is then responsibility of drug manufacturer to
ensure that contract of the filter and drug
product does not result in any toxic by product
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20. Filter validation performed by drug
manufacturer is not just a regulatory
requirement it also makes good business.
It start with a filter requirements specification
From this specification it is simply a matter of
choosing the method that allow verification of
the requirements
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21. Validation of pharmaceutical process, sterile
products second edition by Frederick J,
carleton,James P,Agalloco. pg no-555-559
Advanced in biotechnology Engineering &
technology by Russell E Madson pg no-125-141
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22. www.springerlink.com
www.gmp.compliance.org
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