Hydro Corr Test

BioPharmaceutical DivisionDiscover the More in Millipore.™

Operator Certification CourseIntegrity Testing Methodology

Hydrophobic filterIntegrity Testing


Integrity testing overview

äParticle basedn Microorganismn Aerosols

äLiquid property based n Alcoholsn Water +\GUR&RUU


Microorganism - Destructive Testn Aerosol microorganisms or liquid bacterial challengen Phage (T1, T3, phiX)n Bacteria (B. diminuta)

Aerosol Based - Non-destructive Testn "Smoke“: D.O.P.(Di-Octyl Phthalate), Glycerol, Corn oil (Dispersed Oil Particulate) etcn Methylene Blue, Sodium Flamen Issues

l Particle Distribution must be uniforml Must have correlation of particles vs microorganismsl High equipment costl Difficult to perform in-situ (particle counter downstream of filter)

Particle Based Integrity Testing


Alcohol testTraditional Testing Principles

ä Typical wetting liquids are Isopropyl Alcohol (I.P.A. or Propanol-2), Methanol, Tert-butyl Alcohol, or a mixture of one of these and water

ä Uses same principles as a hydrophilic test

Diffusion & Bubble point

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ä Changing solvent changes wetting & contact angleä Check alcohol concentration & quality

Alcohol testSolvent Effects on Bubble Point


Alcohol testAdvantages

äNo special equipment requiredäFollows similar procedures to hydrophilic

membranes. Operator training time is reducedäTraditionaläReduced temperature influenceäWidely acceptedäWell understoodäCorrelated to bacterial challengeäCan be performed easily & quickly


Alcohol testIssues

ä Alcohol / Water mixtures are often used due to:l costl flammabilityl high diffusionl possibility of evaporation

ä Secure areas and equipment neededä Can be difficult to perform in-situ

ä Some concerns with residual test solution remaining in filter holder / pipework after testing

ä Residual solution should be removed before filter sterilization


Alternatives to Alcohol Integrity Testing

Needed primarily due to:n Issues with alcohol contamination of processes

l residuesn Risks inherent with the use of solvents

Water-Based Integrity Tests have been developed to overcome these issues

n Ease of use


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Water testWater-Based Integrity Test Basis

äHydrophobic polymers repel water

äWater Intrusion PressureThe minimum pressure necessary to force water into the largest pores of a hydrophobic membrane.

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Water testResistance to water intrusion

•Force water under pressure onto

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•Applied pressure is < integral

filter intrusion pressure

•The water pressure is maintained

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• If integral, the upstream pressure

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HydroCorr test

n Applicable for all types of hydrophobic testable membranes

n Correlated to bacterial Challenge

n To be conducted on a perfectly dry membrane

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Water testPerforming Water-Based Tests

ManuallyUse a flow meter to measure actual upstream water displacement

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Water testAutomated water based testing

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Water testWater-Based Test Considerations

äMust have a leak-free systemäFilters must be dry and cleanäTemperature changes should be minimizedäReference testing is importantäMust have a complete validation packageäValues must be comprehensively correlated to

microorganism challenge

Hydro Corr Test

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