High Voltage Leak Detection

High Voltage Leak Detection (HVLD) is a deterministic, non-destructive leak testing method used for evaluating the container closure integrity of liquid-filled pharmaceutical packaging.

The method uses the electrical conductivity of a liquid product inside a non-conductive container. A high-voltage electrical field is applied across the package. If a pinhole, crack or closure defect creates an electrical pathway between the product and the external electrode, the resulting change in current can be detected by the HVLD system.

High Voltage Leak Detection is particularly suitable for pharmaceutical applications where rapid, objective and highly sensitive container closure integrity testing (CCIT) is required.

 

High Voltage Leak Detection for CCIT

 

High Voltage Leak Detection is widely used as a container closure integrity testing method for liquid-filled pharmaceutical products.

USP <1207> provides guidance for the integrity assurance of nonporous sterile pharmaceutical packages and addresses selection, development, validation and use of leak test technologies throughout the package lifecycle.

For an HVLD method to be suitable for a specific product-package system, its detection capability should be established and validated according to the package configuration, product characteristics and required Maximum Allowable Leakage Limit (MALL).

Typical applications include:

● Package development
● Container closure system qualification
● Filling and sealing process validation
● Production quality control
● Stability studies
● Transportation studies
● Packaging defect investigation
● 100% production inspection where appropriate

 

What Packages Are Suitable for HVLD Testing?

 

High Voltage Leak Detection is primarily used with liquid-filled pharmaceutical containers made from electrically non-conductive packaging materials.

Common applications include:

● Glass ampoules
● Pharmaceutical vials
● Prefilled syringes
● Cartridges
● Blow-Fill-Seal (BFS) containers
● Plastic bottles
● Selected liquid-filled pouches

HVLD is particularly useful for detecting defects such as:

● Pinholes
● Micro-cracks
● Wall defects
● Seal defects
● Closure leakage
● Defects around container interfaces

The suitability of the method depends on both the package material and the electrical properties of the product inside the package.

 

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 High Voltage Leak Detector

For pharmaceutical manufacturers and laboratories that need to perform High Voltage Leak Detection (HVLD) on liquid-filled packages, Zholion recommends the MC-E23 High Voltage Leak Detector.

The MC-E23 is designed for leak detection of liquid-filled, electrically conductive pharmaceutical packages and can be configured for suitable:

● Ampoules
● Pharmaceutical vials
● Prefilled syringes
● Cartridges
● Other liquid-filled containers

Using the HVLD principle, the MC-E23 provides rapid, non-destructive package integrity testing without the need for tracer gas preparation. It can support pharmaceutical packaging development, CCIT method development and routine quality control.

Recommended for: Liquid-filled pharmaceutical packages requiring High Voltage Leak Detection and CCIT.

 

 

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.

 

 

Applications in Pharmaceutical Packaging

 

Ampoule Leak Testing

Glass ampoules are well suited to High Voltage Leak Detection because the glass provides an electrically insulating barrier while the liquid formulation can provide the conductive pathway required for detection.

HVLD can be used to detect cracks and pinholes that could compromise ampoule integrity.

Vial Leak Testing

For suitable liquid-filled glass vials, HVLD can evaluate potential defects in the container and closure system.

Electrode configuration and liquid contact with the target inspection area should be evaluated during method development.

Prefilled Syringe Leak Testing

High Voltage Leak Detection can also be applied to suitable prefilled syringes and cartridges.

Testing may focus on potential leakage paths around the syringe barrel, closure interfaces and other critical package areas.

 

Advantages of High Voltage Leak Detection

 

HVLD offers several advantages for pharmaceutical package leak testing:

● Non-destructive test method
● Objective instrument-based results
● Rapid testing cycle
● No dye solution required
● No microbial challenge required
● Suitable for automation
● Can support high-throughput inspection
● Applicable to various liquid-filled pharmaceutical containers
● Can detect very small defects when properly developed and validated

HVLD technologies are used for container closure integrity testing of applications including prefilled syringes, vials, cartridges, ampoules, BFS containers, bottles and pouches.

 

HVLD vs. Vacuum Decay

 

Both HVLD and vacuum decay are deterministic methods used in pharmaceutical CCIT, but their operating principles and suitable applications differ.

HVLD detects changes in electrical current and is particularly suited to conductive liquid products packaged in non-conductive containers.

Vacuum decay places the package in a test chamber and detects pressure changes caused by leakage. It can therefore be applied to package configurations where electrical conductivity is not suitable for HVLD.

The appropriate test technology should be selected according to the product, packaging material, container geometry, expected defect type and required detection capability.

 

Need Help Evaluating HVLD for Your Packaging?

 

Not sure whether High Voltage Leak Detection is suitable for your pharmaceutical container?

Send us your container type, package material, dimensions, fill volume and product characteristics. Zholion can help evaluate whether HVLD or another CCIT technology is appropriate for your application.

Contact Zholion for High Voltage Leak Detection and CCIT Support.