Integrity testing for single-use bioreactor and bags Upstream Day

Transcription

1 Integrity testing for single-use bioreactor and bags Upstream Day Jörg Weyand, Application Specialist Fermentation Technologies Page 1

2 Agenda 1. Introduction 2. Test Principle 3. Porous Spacer Design 4. Validation Approach 17/05/2013 page 2

3 STR bag testing for ultimate process safety & business risk mitigation Security, check bag conformity after shipment and installation, prior use Avoid potential loss of filled bioreactor volume (40k USD for 1,000 l bag) Avoid cost and time for cleaning and re-installation of system Maintain production schedule, deliver product on time, take manufacturing off the critical path (could be worth millions of Euro Dollar) Optimal plant utilization Page 3

4 Integrity Testing CultiBag STR Test principle

5 Integrity Tests of CultiBag STR Rational and Test method Observed Defects Most defects are based on handling mistakes. Known defects are in 0.5 to 3.0 mm range. Objective Detection of macroscopic defects after installation and prior to use. Test bag in place, directly before use. Test method description Porous spacer installed between bag and tank to prevent blocking of defects. Bag installed in a tank Bag with sterile vent filter for test gas application. Pressure drop test Page 5

6 Point-of-use test set-up of installed STR bag Sartocheck 4 plus Bag tester STR bag in holder Fleece in bag holder Page 6

7 Integrity Tests of CultiBag STR Additional Benefits All connections up to the final clamp can be tested for integrity. This includes connected probes, connected tubes up to the clamp and cable tie connections Page 7

8 Porous Spacer Design Spacer development for integrity testing of CultiBag STR

9 Installation of Porous Spacer Part Identification Door cover Bottom cover Page 9

10 Secure detection of potential defects A fleece fitting exactly to the STR holder geometry is installed before testing Avoids direct contact of the bag to the holder during pressure drop test Eliminates masking effect and reduces environmental heat transfer Potential leaks are securely detected Page 10

11 Integrity Testing CultiBag STR Validation Approach

12 Initial Tests CultiBag Test Setup 50 L 200 L Simplified prototype bag 50 L or 200 L with only one bottom line for filling Welded patch with laser drilled defect of 500 μm on a surface touching the tank doors Porous spacer on the door where the defect patch is located. Multiple tests are performed with - the defect closed with tape and an additional layer of film between the defect and the tape to prevent the defect to be altered by the glue - open defect Page 12

13 Initial Tests CultiBag Test Setup Defect closed defect open defect Page 13

14 Integrity Tests of CultiBag STR Validation Approach First phase : Determination of detection limit on prototype bags 1. Repeated tests with non-defective bags. 2. Repeated tests of bags with master leak patches of different leak diameters Second phase : Verification of reproducibility, repeatability and robustness of the test method 1. Tests on a statistically significant number of standard bags from different lots. a) non-defective bags b) bags with master leaks of the determined detection limit 2. Perform multiple test repeats on the bags from 1). 3. Perform tests on multiple worst case conditions e.g. temperature, volume variation Page 14

15 Integrity Tests of CultiBag STR Validation Approach (Sample Data) Test result analysis no defect Detection of 100 μm defect not possible as the six sigma range is within the LOQ range. Detection of 200 μm defect is possible under controlled conditions and with trained personnel providing robust process safety. pressure Pressure drop Drop [mbar] counts [-] Counts [-] ,5 100 µm 300 µm 1,5 3,5 5,5 7,5 9,5 11,5 13,5 15,5 17,5 19,5 21,5 23,5 25,5 27,5 mean no defect (Blind value) Mean 100µm mean 200µm Six-Sigma 200 µm pressure drop [mbar] pressure drop (classes) [mbar] 29,5 0 LOQ Test time [s] test time [s] Page 15

16 SSB has the most advanced bag test solution on market SSB ATMI ASI Method Pressure decay Helium in closed chamber Pressure decay Test location point-of-use before installation point-of-use Test time 90 min ~ 10 min 30 sec (= too short to detect anything) Sensitivity ? Remarks Detection of leaks across complete surface due to patented fleece Qualified test method Cost efficient Only for 2D bags Gas permeability of tubing affects results Expensive equipment & He No porous spacer Masking effect no secure detection The Sartocheck Bag tester is the best test unit for point-of-use testing of 3D bags The STR with patented fleece is only SU bioreactor that can be tested reliably Page 16

17 Thank you for your attention. Any Questions? Jörg Weyand, Sartorius Stedim Biotech, Application Specialist, Fermentation Technologies, Central Europe