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Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale[Department of Pharmaceutics][Department of Pharmaceutics]

avengersagar16@gmail.com2015-20162015-2016

Why Validate?

What needs to be Validate?

Who is responsible for Validation

Elements of validation study Conclusion

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Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic

For Good business PracticeA control process gives reproducibility &

product consistency with in known limits

Provides license to do business.

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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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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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Reproducibility Sterlization Operating Condition Particulates Fibers Microbial Retention Filter Inertness Drug Product stability Endotoxin Toxicity

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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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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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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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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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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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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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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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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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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 107 Brevundimonas diminuta per square centimeter of filter area will produce a sterile effluent.

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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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Drug product stability should not affected by filtration

It affects loss of activity, lowering of activity or conformational changes

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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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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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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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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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www.springerlink.com www.gmp.compliance.org

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