Blogs

Packaging has always been an indispensable factor in the pharmaceutical manufacturing process. Since most pharmaceutical products come under high-risk category, appropriate packaging is vital to prevent product deterioration. Faulty or damaged packaging can cause oxygen, moisture, microorganisms or other harmful substances to enter the product- making it unfit for use. Given the sensitive nature of pharmaceutical products, package inspection testing holds high relevance. Let us now understand what CCI techniques are being offered by PTI for pharmaceutical package testing.

Techniques to ensure CCI

1. Vacuum Decay technology

Vacuum Decay is a non-destructive Container Closure Integrity Test (CCIT) method that is highly effective in detecting leaks in nonporous, rigid and flexible packages. It is a simple test method that challenges container integrity based on fundamental physical properties. As the name suggests, this test is conducted by drawing vacuum on a package within a test chamber and monitoring the vacuum level for any decay, which would indicate a leak. The standard vacuum decay leak test method (ASTM F2338), developed using PTI's VeriPac instruments, is recognized by the FDA as a consensus standard for container closure integrity (CCI) testing. The test method is listed in ISO 11607 and referenced in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207). PTI has revolutionized Vacuum Decay technology with its s next generation of improvements in the form of PERMA-VAC technology and VeriPac FLEX Series.

PERMA-VAC Technology is a single or dual vacuum transducer technology, which has higher test sensitivity for providing accurate and reliable results. This method can be applied to flexible and semi-flexible packages alike.

The VeriPac FLEX series are innovative packaging inspection systems specifically for flexible packages. These are available in different configurations to accommodate various package specifications, capable of detecting leaks down to the 10 to 20 micron range.

Benefits of Vacuum Decay technology

2. MicroCurrent HVLD Technology

High Voltage Leak Detection (HDLV) is a Container Closure Integrity test method that utilizes high voltage leak detector system for evaluating integrity of nonporous packages. The latest evolution in the HVLD technology, PTI’s MicroCurrent HVLD is revolutionary technology, a non-destructive, non-invasive CCI technique which can precisely detect any leak in a wide range of liquid filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions.

This method operates by scanning a sealed container using electrode probes to detect the presence of any leak. By analyzing a change in the current flow, the test operator can detect Defect in the container as well as its approximate location. PTI's MicroCurrent HVLD uses about 50% less voltage and exposes the product and environment to less than 5% of the voltage compared to conventional HVLD technologies. This technology can be easily shifted from offline to 100% inline testing application, thereby simplifying the inspection and validation process.

Benefits of MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation
• High level of repeatability and accuracy
• Effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Low voltage exposure to the product and environment
• Listed in USP Chapter <1207> as recommended method for parenteral liquid package inspection
• Robust method and approximate 3x Signal-Noise-Ratio for a wide range of product classes and package formats
• Simplifies the inspection and validation process
• Offline and 100% online inspection at high production speeds

The rapidly increasing preference towards combination pharmaceutical products continues to fuel innovation, while presenting unique challenges in implementing a container closure integrity (CCI) testing strategy. Common examples of combination products include prefilled syringes, pen injectors, inhalers, and drug-eluting stents, orthopedic products, infusion pumps and more. The packaging for combination products can be just as complex as the products themselves. Hence, container closure integrity testing in line with current USP <1207> guidance and regulation is critical to ensure package integrity.

Techniques to ensure CCI: Helium leak testing & Microcurrent HVLD technology

Helium leak testing refers to the process of finding leaks in some type of enclosed or sealed system using helium as a “tracer” gas and measuring its concentration as it escapes due to leakage. Apart from being an ideal solution for ensuring Container Closure Integrity, the technology is also applicable in package design, monitoring product quality, failure analysis and line set up and validation.

Under this method, a helium leak detector otherwise known as Mass Spectrometer Leak Detector (MSLD) is used to identify and calculate size of the leak. The test part is first connected to a leak detector and then the tracer gas, helium is introduced. In the presence of a leak, helium escapes from the test parts and this partial pressure is measured and results are displayed on the meter. Helium Leak Detection per ASTM F2391, has long been recognized by the FDA as a consensus standard for package integrity evaluation. The test method is also referenced in the United States Pharmacopeia (USP) Chapter on Container Closure Integrity (CCI) – USP <1207>.

PTI’s MicroCurrent HVLD technology is a non-destructive, non-invasive container closure integrity test method that is found to be highly effective across applications such as pre-filled syringes, vials, cartridges, ampoules, BFS, bottles and pouches. This technique can precisely detect any leak in a wide range of liquid-filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. Under this method, the sealed container is scanned using electrode probes to detect the presence of any leak. Defects in the container as well as its approximate location can be identified by analyzing a change in the current flow. MicroCurrent HVLD technology utilizes about 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. It is one of the most effective CCI technologies for all parenteral and biologic products.

Benefits of PTI’s MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation
• Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Ensure higher levels of accuracy and reliability in results
• Offline and 100% online inspection at high production speeds
• Simplifies the inspection and validation process
• Referenced in USP 1207 Guideline

Over the years, there has been a steady increase in the demand for pre-filled syringes for injectable drug products that can be self-administered. However, considering the complex nature of pre-filled syringes, Container Closure Integrity assurance can be quite challenging. Container Closure Integrity is understood as the ability of containers to maintain a sterile barrier against possible contamination. A leak or breach in the sterile barrier can rapidly convert a lifesaving drug into a threat for patients. Parenteral products are the highest risk of all packaging formats. Vials, ampoules, and pre-filled syringes have the highest potential for microbial growth, and the risk to the end patient amplifies the focus needed on CCI for these applications.

High Voltage Leak Detection (HVLD) has been in the market for decades. However, PTI’s MicroCurrent technology has revolutionized HVLD. MicroCurrent HVLD  aims to achieve a high level of CCI assurance across the entire range of parenteral products. High Voltage Leak Detection is a deterministic test method included in USP 1207, and is an established and reliable solution for all liquid filled parenteral products.

Pre-filled syringe testing using HVLDmc (E-Scan 655) technology

The E-Scan 655 is a Microcurrent HVLD technology-based leak test instrument used to inspect vials, syringes, and other liquid filled parenteral products. It is a non-destructive conductivity test method, exposing the package and product to lower voltage than other conductivity-based solutions.

The E-Scan 655 features a fast test cycle and simple operation. It can accommodate a wide range of applications and products, including low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. The technology uses a non-contact, non-invasive test method that requires no sample preparation. Additional benefit include ability to migrate from laboratory to 100% inline testing applications at high production speeds.

Technology Overview

The E-Scan testing process uses a set of electrode probes to scan a non-conductive container that is sealed. The container material can be glass, plastic, or poly laminate. The container or package must contain liquid (minimum fill 30%). In the presence of a pinhole, crack, or other defects, there will be a resistance differential and change in current flow, indicating a breach in the container. The approximate defect location can be identified.

Benefits of MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation
• High level of repeatability and accuracy
• Effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Lower voltage exposure produces no ozone, eliminating risk to the product and environment
• Listed in USP Chapter as recommended method for parenteral liquid package inspection
• Robust method and approximate 3x Signal-Noise-Ratio for a wide range of product classes and package formats
• Simplifies the inspection and validation process