Introduction

Integrity testing is a non-destructive method used to verify the performance and reliability of filter membranes. Especially in pharmaceutical and biotechnology industries, integrity tests confirm that sterilizing-grade filters are intact and capable of retaining microorganisms, ensuring compliance with GMP and regulatory standards.

1. Purpose of Integrity Testing

• Verify the integrity and proper installation of membrane filters before and after use.
• Provide documented proof that filters maintain their microbial retention capability.
• Detect possible damages such as cracks, pinholes, or improper sealing.
• Comply with FDA, EMA, and ISO validation requirements for sterile filtration processes.

2. Basic Principle

The integrity test is based on measuring gas flow or pressure changes through a wetted membrane. As gas is applied to one side of the filter, any discontinuity (defect or open pore) will allow gas to pass, and this flow behavior is detected and analyzed.

3. Common Integrity Test Methods

3.1 Bubble Point Test

The bubble point is the pressure at which gas begins to displace the liquid from the largest pores of a wetted membrane. It reflects the maximum pore size of the filter.

Formula:

从表面张力与孔径关系出发：

$$ P_b = \frac{2 \gamma \cos\theta}{r_{max}} $$

其中：

• $ P_b $：气泡点压力（Pa）
• $ \gamma $：液体表面张力（N/m）
• $ \theta $：接触角（°）
• $ r_{max} $：最大孔径（m）

> 1. 当系统中气压升高到超过 $P_b$ 时，最大孔道内的液体被气体排出，连续气泡出现； > 2. 仪器监控气体流量突增，即为气泡点出现； > 3. 气泡点越高，孔径越小，过滤精度越高。

3.2 Diffusion Flow Test

Below the bubble point, gas diffuses through the wetted pores. The diffusion rate is measured and compared to standard limits. Excessive diffusion indicates potential damage or enlarged pores.

> 1. 在低于气泡点的稳定压力下记录气体流量； > > 2. 若实测扩散流 $Q_{measured}$ ＞ 合格标准 $Q_{limit}$，说明滤膜有缺陷或润湿不完全； > > 3. 此法灵敏度高，可检测微孔级损伤。

3.3 Pressure Hold (Decay) Test

This method measures the rate of pressure decrease in a closed chamber after a defined stabilization period. If the pressure decays faster than the limit, leakage or membrane defects are suspected.

> 1. 加压 → 稳压 → 计时； > > 2. 记录 $ \Delta P / \Delta t $； > > 3. 若下降速率超过标准，即视为不合格。

4. Test Conditions and Requirements

• Use clean, dry, non-reactive test gas (usually compressed air or nitrogen).
• Ensure filter is properly wetted with relevant test liquid (water, isopropanol, product fluid).
• Perform test before and after filtration process for validation.
• Automatic integrity testers are recommended for traceable digital documentation.

5. Applications

• Pharmaceutical Filtration: Sterile filtration of drug solutions, ensuring sterilizing-grade performance.
• Biotechnology: Validation of filters in cell culture and vaccine production.
• Food & Beverage: Sterile liquid filtration for beer, wine, and dairy.
• Microelectronics: Membrane integrity assurance for ultrapure liquid filtration.

6. Importance of Validation and Documentation

Regulatory agencies require documented integrity testing as part of process validation. Integration with automated digital logging systems ensures data transparency, traceability, and reproducibility for GMP audits.

Conclusion

Integrity testing confirms that sterilizing filters perform as intended. Methods such as bubble point, diffusion flow, and pressure hold ensure scientific verification of membrane quality and guarantee product safety throughout filtration-based production processes.

Purchase Suggestion

Contact our technical team for selecting appropriate integrity testing equipment and protocols compatible with your filtration systems and regulatory requirements.