High Voltage Leak Detection

Test Principle

The test principle of high voltage leak detection (HVLD) exploits the electrical conductivity of liquid drug products that are packaged in containers made of non-conductive materials (e.g., glass, plastic, or poly-laminate). A high-frequency voltage potential is applied to the container by means of suitable electrodes, and the discharge current is measured by the system.The resulting resistance differential and change in current flow through the liquid indicate the presence of a container seal defect.

Test Equipments in Our Lab

PTI E-scan 655, Argo Series, Zholion MC-E23

Regulatory Requirements

USP<1207>

USP <1207> lists HVLD as a deterministic test method for container closure integrity testing. Deterministic methods are preferred over probabilistic methods.

High voltage leak detection (HVLD) is listed as a deterministic method alongside laser headspace analysis and pressure/vacuum decay methods.

USP <1207> strongly recommends deterministic methods over traditional probabilistic methods due to their sensitivity, objectivity, and reproducibility.

Method validation requires demonstrating the ability to reliably detect leaks at the product's Maximum Allowable Leakage Limit (MALL). USP <1207> specifies that "for the validation of a method it will be important not only to build on the qualification of the testing device, but to examine the different packaging/product combinations, for example with and without defects".

USP <1207> applies to vials, ampoules, syringes and bags, with certain concepts transferable to active substances, intermediate or bulk materials in storage.

ASTM F2338

USP <382> replaces USP <381> and expands the scope of testing from the elastomer component alone to the complete container closure system. USP <382> points directly to USP <1207> for container closure integrity testing methodologies.

USP <382> requires system-level integrity assessment. Deterministic CCIT methods—such as vacuum decay or high-voltage leak detection—are required to demonstrate closure integrity.

The USP <382> deadline of December 1, 2025, mandates the transition to system-level CCIT using deterministic methods

EU GMP Annex 1

EU GMP Annex 1 requires 100% integrity testing for fusion-sealed containers and recommends HVLD as a validated CCI method.

For fusion-sealed containers (e.g., glass ampoules, BFS), manufacturers must implement 100% container closure integrity testing. Visual inspection alone is insufficient to check container integrity.

HVLD is specifically recommended as a validated method in both Annex 1 and USP <1207>.

Annex 1 Chapter 8.22 emphasizes the importance of CCIT to ensure the safety and quality of pharmaceutical products. The guideline requires 100% integrity testing for fusion-sealed containers (up to 100 ml). One of the methods adaptable for commercial use is high-voltage leak detection (HVLD)

Annex 1 Chapter 8.23 clarifies that products using systems other than fusion must also be tested for integrity using validated methods.

The revised Annex 1 (effective August 2023) is harmonized with WHO and 56 PIC/S member countries, significantly increasing its global relevance and impact.

Packaging System Integrity Study Guidance(China)

China NMPA has published the "Technical Guideline for Packaging System Integrity Study of Chemical Injectables (Trial)", which aligns with international deterministic CCI methodologies.

The guideline references USP <1207> and deterministic CCIT methods, with method validation required to demonstrate detection capability relative to the product-specific MALL. HVLD is recognized as a validated physical integrity test method for liquid-filled container closure integrity testing.