Trinity Engineering Whitepaper
Executive Summary & Key Takeaways
- In-situ forward flow diffusion is preferred over bubble point for large surface multi-round filter housings (> 1 m²).
- Ensure complete wetting using validated flush volumes (minimum 3 L/min per 10" cartridge at 2.0 bar for 5 minutes).
- Water Intrusion Testing (WIT) eliminates solvent wetting requirements for hydrophobic PTFE vent and gas filters.
1. Non-Destructive Integrity Test Methods Overview
Sterilizing-grade 0.22 µm and 0.1 µm hydrophilic Polyethersulfone (PES) filters must be validated to achieve complete retention of Brevundimonas diminuta (ATCC 19146) at a challenge concentration ≥ 10⁷ CFU/cm² of effective filtration area.
| Integrity Test | Physical Principle | Recommended Scope | Key Advantage |
|---|---|---|---|
| Bubble Point (BP) | Capillary pressure overcome: P = 4γ cosθ / d | Single 10" - 30" small volume housings | Fast, direct pore size correlation |
| Forward Flow Diffusion | Fick's law gas diffusion through liquid-wetted pores | Multi-round housings (3-round to 30-round) | High sensitivity for large surface areas |
| Water Intrusion (WIT) | Hydrophobic pore resistance to liquid water penetration | Hydrophobic PTFE gas & vent housings | No alcohol or IPA wetting solvent needed |
2. Step-by-Step PES Wetting Protocol
Over 80% of integrity test false failures in bio-manufacturing are caused by incomplete wetting of the membrane pores. Follow this validated protocol:
- Install cartridges using food-grade USP Class VI silicone or EPDM O-rings lubricated with sterile WFI.
- Flush housing with Water-For-Injection (WFI) at 2.0 - 2.5 bar differential pressure with upstream and downstream vents cracked open.
- Maintain forward flush for 5 to 10 minutes at a minimum flow rate of 3.5 L/min per 10-inch element.
- Perform a rapid back-pressure pulsation (close downstream valve for 3 seconds, reopen) to expel trapped micro-bubbles from the pleat pleats.
3. Troubleshooting False Failures in Cleanrooms
If an automated integrity tester reports a diffusion value exceeding the maximum allowable limit (e.g. > 18 mL/min at 2.4 bar for a 10" PES cartridge):
- Check O-Ring Seals: Inspect 226 or 222 double O-rings for rolling, nicks, or particulate contamination on the housing receiver tube.
- Verify Fluid Temperature: Gas diffusion rate increases significantly at elevated temperatures. Test should occur at 20°C ± 2°C.
- Rewet at Higher Differential Pressure: Flush for an additional 5 minutes at 2.5 bar and re-test.