Aug 2021

How to Ensure CCI of Combination Products

How to Ensure CCI of Combination Products

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

1. Helium leak testing

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>.

2. Microcurrent HVLD technology

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
cci, pre filled syringes, helium leak testing, microcurrent hvld technology, container closure integrity testing
Jan 2021

How can Helium Leak Detection Technology Ensure Pharmaceutical Package Integrity?

How can Helium Leak Detection Technology Ensure Pharmaceutical Package Integrity

Over the last two decades, pharmaceutical industry has seen tremendous growth in the form of technological advancements and drug delivery system innovations. However, such innovations have increased quality assurance challenges for drug manufacturers. For this reason, drug product manufacturers give at most importance to their quality control procedure as well as package integrity tests.

Packaging plays a vital role in preserving product quality and maintaining a sterile barrier against external damaging force. Even a minute breach in the package can cause moisture, reactive gases, or other harmful substances to enter the product- thus compromising its healing properties. Moreover, a contaminated drug product can cause serious health issues to the user, making it more of a threat than treatment. Given the sensitive nature of pharmaceutical products, ensuring Container Closure Integrity holds high relevance.

Container Closure Integrity testing is a leak detection technique for evaluating the ability of container closure systems in maintaining sterile barrier against external contaminations. Such tests can be broadly classified into Probabilistic and Deterministic test methods. Although Probabilistic test methods like Bubble Tests and Dye Ingress were initially popular, with more technical advances, better, non-destructive methods are now the go-to solutions to insure container integrity. Manufacturers are encouraged to switch to more reliable Deterministic test methods that provide guaranteed quantitative results with precision. In this blog we will be discussing in detail Helium Leak Detection Technology.

What is Helium Leak Detection Technology?

Helium Leak Detection Technology is a Container Closure Integrity test method that is used to find leaks in different types of enclosed or sealed systems. The technique uses helium as a tracer gas and its concentration is measured as it escapes through the leaks. Under this method, the package is helium filled and subjected to vacuum. The amount of helium escaping the package is quantitatively measured and stated as a leak rate. Helium is an ideal choice for package leak testing and container closure integrity testing in particular during container closure development for pharmaceutical products, due its key qualities:

  • It is inert, non-toxic, non-condensable and non-flammable.
  • Being inert, it is safe to use as it will not react with other materials being tested.
  • The atom size of helium is really small therefore it can easily pass through leaks.
  • The instrument noise due to environmental helium is inherently low because of its limited presence in the atmosphere at less than 5ppm and thus gives incredibly accurate reports.
  • Helium is relatively inexpensive and is available in multiple cylinder sizes.

Seal Integrity Monitoring System

The Seal Integrity Monitoring System (SIMS) 1915+, is the ideal choice for your helium-based leak detection system for testing rigid containers including vials, syringes, and cartridges and blister cards. Using helium as the tracer gas, packages can be quantitatively tested to levels far exceeding the vacuum bubble and dye penetration test methods. This quantitative approach allows direct comparison across various packaging materials and forms, production line settings and stability storage conditions, supporting the entire lifecycle.

THE SIMS 1915+. features an oil-free detector and power system that is designed for the needs of the pharmaceutical and medical device industries. In addition, this system will enable you to quantitatively analyze package system at a sensitivity level as low as 1 x 10 -11 mbar-L/s and provides relevant data sets in place of a simple pass/fail criteria while enabling testing to be performed at room temperature.

Each SIMS 1915+ Helium Leak Testing instrument manufactured by Leak Detection Associates is custom built to client specific standards and package configurations.

Custom Built to Client Specification SIMS 1915+ Leak Detection System with Add -On Components

  • Helium Leak Detector Module (HLDM): Oil Free, Production version in Console Frame Assembly, with Stainless Steel working surface and Dual Test Port Manifold (allows concurrent use of VTFM & HSAM on HLDM unit).
  • Vacuum Test Fixture Model (VTFM) – custom designed for use in testing of vial container samples
  • Head Space Analyzer Module (HSAM) – Model VM-2 that includes three (3) Puncture Probes (two spares) for determination of Helium Concentration in the headspace of vial containers.
  • Integral Calibration Chamber (w/ Calibrant Gas Flow Meter/Controller) provided for HSAM Calibration and a Universal Holder to be used for various vial diameters.
  • Helium Filling Device specific for vial testing sample prep to enable vials to be filled with helium
helium leak detection technology, helium leak testing, helium leak detector, helium leak detection, pharmaceutical package integrity, helium leak detection solutions

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