Good Manufacturing PracticeFor 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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Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale
[Department of Pharmaceutics][Department of Pharmaceutics]
avengersagar16@gmail.comavengersagar16@gmail.com
2015-20162015-2016
Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale
[Department of Pharmaceutics][Department of Pharmaceutics]
avengersagar16@gmail.comavengersagar16@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 107
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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