Introduction to sterile filtration

1. STERILE FILTRATION
- Paulus Hartanto -

2. Filtration Spectrum

3. Major Markets
 Pharmaceutical Industry
 Bio-Technology
 Food and Beverage
 Hospital & Home Patient Protection

4. Pharmaceutical Industry
 Injectables
 Diagnostic solutions
 Pre- and final filter for bacteria
and virus removal/reduction
 Fermentation air intake
 Bio-processing exhaust air

5. Food and Beverage
 removal of bacteria, yeast and other
contaminants from wine, beer and
bottled water
 production of soft drinks
(e.g. carbonated drink, juice)
 filtration of process water and
process gas

6. The two major ways of filtration
Depth retention Surface retention

7. What retains the particles?
sieve effect
Brownian molecular
movement
0.3 µm
retention minimum
Efficiency (%)
Particle size (µm)

8. ßx
=
NF ≥ Size X
NP ≥ Size X
= ß2
=
100
2
50=
Example
BETA RATIO is the ratio of the
number of particles of a given size
and larger in the feed to a filter to
the number of particles of the same
size and larger downstream.
Definition of Beta Ratio

9. Particle Removal Efficiency
% Removal and Beta Ratio
% Removal
Efficiency
Feed - Product
=
Feed
=
100 - 2
100
= 98%
Beta Ratio =
Feed
Product
=
100
2
= 50
% Removal
Efficiency
(Beta – 1)
=
Beta
=
50 - 1
50
= 98%
Beta Ratio =
1
1 - Efficiency
=
1
(1 – 98)
= 50
=
50
49
Example

10. Efficiency and Beta Ratio
Relationship
Beta Ratio % Efficiency
1 0
2 50
4 75
5 80
10 90
20 95
50 98
75 98.67
100 99
1,000 99.9
5,000 99.98
10,000 99.99
∞ 100

11. Nominal Vs. Absolute Rate
Nominal Retention Rates
Rate relating to an average contamination size.
Not applicable to assess filter quality
• Various test methods and assessments on the market
• No data about the largest contamination passing through
Absolute Retention Rates
A filter is called “Absolute” if the so called ß – value is > 5000
• ß = Quantity of particles [challenge]/Quantity of particles [filtrate]
• The higher ß, the better the retention rates
• Sterile Filter: ß > 10exp7 (0,2µm)

12. Filter challenging method refined in 1983, by ASTM
(American Society for Testing and Materials)
• ASTM standard F 838-83 (renewed in 2005)
• Pore size: 0.2 (0.22) µ
• Brevundimonas diminuta: the challenging microorganism
• LRV (log reduction value) = 7 per cm2
equal to: 107 contaminations per cm2 filtration area.
Efficiency– Sterile Grade







filtrate)theinorganismsof(Number
aerosol)/suspensiontesttheinorganismsof(Number
logLRV

13. Sterilizing grade filter 1st defined FDA, in Jun. 1987.
(FDA Guidance for Industry – Sterile Drug Products
Produced by Aseptic Processing )
Efficiency– Sterile Grade
LRV >/= 7/cm2 or 99,99999% per cm2 for contaminations of 0,2µm – 0,3µm
are the only acceptable and FDA approved definitions of a sterile filter

14. Retention Mechanisms: Air/ Gas filter
 Retention Efficiency is lowest between 0,2µm – 0,3µm
 Area is called MPPS Range (Most Penetrating Pore Size)
 FDA Definition is based on Retention Efficiency in this range
 Integrity tests (DOP Test) carried out at 0,2µm – 0,3µm
Efficiency Vs. Particle size

15. Sterilisation
 Bacteria survive inside the filter media
and must be killed by means of slow
velocity dry steam (saturated or
overheated)
 Only pre-filtered steam for sanitation.
 Minimum Temperature 121° C/250° F
(131° C/ 268° F or 141°C/ 286° F).
 Minimum time 30 minutes (20 min or 10
min).
 At least once a week or preferably when
the whole system is being sterilised.

16. Summary
Sterile Filter :
• Retain the bacteria mechanically
• Can be & must be sterilized (by
autoclave or SIP)
• No chemical adding for disinfection
or regeneration

17. Thank you