MACTER INTERNATIONAL (Pvt.) LTD.

STERILE PRODUCTS DEPARTMENT

EYE & EAR DROPS SECTION

STANDARD OPERATING PROCEDURE

Title: S.O.P OF INTEGRITY TESTING OF STERILISATION Doc. No.: E/E /3/ EE-020
GRADE LIQUID FILTERS.
Prepared By: AM Issue No.:1
Reviewed By: QAM Issue Date: 12-2-2001
Approved By: DQO DP Page: 1 of 2

1.0 INTRODUCTION

The Bubble Point is the direct measure of the pore size and Integrity of the finest filter
in the system and is a nondestructive test procedure for membrane filter system.
The bubble point pressure is dependent upon:

a) The pore size of the finest filter in the system, with typical values are,
>3 bar for 0.2 um pore size.
>2 bar for 0.45 um pore size. Etc.

b) The wetting liquid.

c) The material of which the filter is made ( 0.2 µm cellulose acetate filter about 4
bar ).

D) The temperature ( a bubble point at 80 oC may be about 60 % less, one at 60o C

about 20 % less than at 20 oC.

2.0 PURPOSE

In critical filtration the user must be able to check that the filtration system is inn
perfect working condition. A nondestructive test must be able to show that the system
is correctly assembled, without leaks, and confirm the integrity of the filter itself.

3.0 FREQUENCY

Compliance with CGMP guidelines requires such integrity testing (BUBBLE POINT)
before and after filtration.

4.0 PROCEDURE

4.1 Confirm that the equipment is labeled correctly and that, for product the details on the
aseptic area section of the batch records are the same as those on the manufacturing
area.
4.2 The filter in the cartridge filtration is thoroughly wetted (e.g. by the standard distill
water rinse ), and the system drained on the inlet side.

4.3 Connect the filter to the pressure vessel.

 MACTER INTERNATIONAL (Pvt.) LTD.
STERILE PRODUCTS DEPARTMENT
EYE & EAR DROPS SECTION

STANDARD OPERATING PROCEDURE

Title: S.O.P OF INTEGRITY TESTING OF STERILISATION Doc. No.: E/E /3/ EE-020
GRADE LIQUID FILTERS.
Issue No: 1 Issue Date: 12-2-2001 Page: 2 of 2

4.4 A piece of narrow tubing is attached to the outlet – side valve, and free end of this
dipped in a bowel of water.

4.5 With inlet – side vent valve closed, the outlet valve is opened and a pressure of about
70 % of the minimum expected bubble point applied at the inlet.

4.6 The pressure is slowly increased ( at the rate of about 0.1 bar every 5 seconds ) until a
continuous stream of bubbles is visible in the bowel. This is the bubble point ( should a
few bubbles appear irregularly as pressure as pressure is first applied, these can be
neglected, they are due to setting within the system ).

4.7 On completion of the integrity test, remove piece of narrow tubing from the outlet side
of the valve and filter the bulk solution using nitrogen pressure. Assist the aseptic area
operator in ensuring that all air is bled from the system.

N.B. The personnel performing the cleanings / maintenance and The personnel
checking those works must sign along with the date the time started and time
when work was completed on the respective log sheets.

FILTER INTEGRITY TEST

(Bubble Point Test)
 Date______________

Batch No ____________ Batch Size ______________ Department ________________

Pore Size Actual Bubble Point

No Remarks
(µm) Pressure (Bar) (Bar)

__________________
Microbiologist