filter validation and regulatory aspects
TRANSCRIPT
Filter Validation and Regulatory AspectsFilter Validation and Regulatory Aspects
Balamurugan m
Balamurugan.m
IntroductionIntroduction
Filtration is a very simple and old technique. Where the separation is based on their physical property (particle Density, Particle Size, electric Charge etc)
Its been used in different stages of fermentation process
Exhaust Filter
Air Filter
Media Filter
TFF, Ultra filter, Dia-filter etc
Regenerated cellulose
Nylon
Polyamides
Polyether Sulfones
Cellulose nitrate
Cellulose acetate
Poly propylene
Poly tetra fluoro ether(PTFE)
Poly Vinyl Denefluoride(PVDF)
HydrophilicHydrophobic
Material Of Construction:Material Of Construction:
Porosity:Porosity:
The total empty space available within the volume of filter is called porosity.
1KG
Porosity:Porosity:
The total empty space available within the volume of filter is called porosity.
1KG water
Porosity:Porosity:
The total empty space available within the volume of filter is called porosity.
1KG1.2KG - = 0.2kg
1.4bar
1bar
Due to resistance Created by the filter
1.4bar
1bar
The difference between the two pressure is called differential pressure
DifferentialDifferential PressurePressure
1.4bar
1bar
Dirt Hold CapacityDirt Hold Capacity
The maximum Dirt it can Hold before the flow rate goes below the acceptable range is called dirt hold capacity
EFA (Effective Filtration Area):EFA (Effective Filtration Area):
The total area of the filter which is involve in the filtration is called Effective filtration area (EFA)
Filter Validation:Filter Validation:
Destructive Test
• Bacterial Challenge Test
Non-Destructive Test
• Bubble Point Test• Diffusion Test• Pressure Hold Test
Bacterial Challenge Test :Bacterial Challenge Test :
Brevundimonas diminuta, ATCC 19146 at 10^7
0.22um0.45um
Bacterial Challenge Test :Bacterial Challenge Test :
Brevundimonas diminuta, ATCC 19146 at 10^7
0.22um0.45um
Bubble point test :Bubble point test :
Bubble point is the minimum The minimum pressure required to force liquid out of a liquid-filled capillary must be sufficient to overcome surface tension and is a direct measure ofeffective tube diameter
Bubble point test :Bubble point test :
Bubble point testBubble point test
Capillary Force
Surface Tension Of water
Pressure is applied
Bubble point testBubble point test
Poiseuille ’ s law
P = Bubble Point Pressure
σ = Surface Tension of the liquid
Θ = Angle between wall and wedding liquid
D = Diameter of the Pore
K = Shape Correction Factor
Diffusion Test:Diffusion Test:
Diffusion Test is generally recommended for high volume filter. (Generally bigger than of 2ft2 or bigger volume)Diffusion of gas is based on the principle that gas will diffuse through the pores of fully wedded filter. This diffusion is propossional to the differential pressure and Surface area of the filter.The pressure maintained is generally the 80% pressure of Bubbling point of the filter.The gas flow rate is determine by measuring the flow rate of water displacement.
D =Diffusiblity of GasH = Solubility of GasΔP = Differential Pressure across The filter cartridgeF= Total Gas Liquid Contact areaL = Thickness of the Liquid film
Diffusion Test:Diffusion Test:Pressure Applied usually 80% of
Bubble Point Pressure
Diffusion of gas Occurs downwards
Diffusion Test:Diffusion Test:
The rate is measured with milliliter of water per second by using a stop clock
This rate is then compared with standard chart
Pressure Hold Test:Pressure Hold Test:
• The pressure hold test is the variation of Diffusion test.• A high accurate pressure gauge is used in the upstream of the filter to measure the pressure lose due to diffusion of through the water. • The pressure hold value is depending on the Gas diffusion and upstream volume of the filter .• It can be calculated by the formula
∆P = D (T) (Pa) Vh
D = Diffusion rate (cc/min)T = Time (minutes)Pa = Atmosphere pressure (1 Atm. or 14.7 psi)Vh = Upstream volume of apparatus (cc)DP = Pressure Drop (bar or psi)
Conclusion:Conclusion:
Filtration validation is the very important technique in Bio-Pharma industry. Currently available techniques validate the filters in indirect way. Many more advancement has to come and validation process has to be done in fast and efficient way.