Nov 2020

Helium Leak Detection for Vial Capping Optimization and Assembly Validation

Helium Leak Detection for Vial Capping Optimization and Assembly Validation

The adoption of deterministic, quantitative test methods for comprehensive container closure integrity testing (CCIT) has become the norm over the past decade. Recent and future regulatory guidance directives have continued this trend. However, this trend of increasing scrutiny, and thus, increasing complexity for regulated companies, is not in vain. The benefits of such a method are plentiful, and their usage can span the entire lifecycle of a product-package system, right from development of the package, to stability, to analysis of package integrity after distribution cycles. In fact, the need for CCIT at multiple product lifecycle stages is explicitly discussed in USP <1207>.

In the current version of USP <1207>, there are a total of four subsections. USP <1207.1> discusses critical background information and rationale for the selection of an appropriate test method. Included in this subchapter is a detailed discussion of CCI evaluation during a product life cycle, which states: “Package integrity verification occurs during [at least] three product life cycle phases: 1) the development and validation of the product– package system, 2) product manufacturing, and 3) commercial product shelf-life stability assessments”. The idea behind such a statement is that CCI should be built into the design of the product-package system and the processes that yield it.

This is a notable shift from the somewhat pervasive tendency to consider CCI as a checkbox, something verified as a company is assembling documentation for a filing, perhaps after the final configuration and manufacturing has been finalized. This latter approach has inherently more risk. What if the vial-stopper configuration chosen does not have an ideal fit? What if the assembly parameters used for capping that vial do not yield consistently integral final packaging? Situations like this are not uncommon, and can lead to expensive changes, product recall, or risk to patient safety. Fortunately, modern, deterministic methods, such as helium leak detection, can help characterize and mitigate these risks.

Early on in the development process, the inherent integrity of the chosen product-package system should be evaluated, essentially answering the question: “Are these components, when mated optimally, capable of creating an integral seal?”. This concept is called inherent integrity, or whether the package components, as an inherent function of themselves, can create and maintain an integral seal. For a manufacturer considering the implementation of a stopper from a potential catalog or stock of many varieties, for example, a helium leak test study can be developed in order to assess the relative performance of each component. In the experience of LDA and its partners, there can be a significant difference between stoppers with the respect to their ability to create adequate seals, regardless of capping conditions. Future blogs in the LDA resource center will highlight these applications.

A specific, upstream and preventive CCI program that is gaining in popularity is that of a “Capping Study”; a program in which optimal sealing parameters are determined through correlation with low leakage rates. In such programs, there are typically a range of sample sets assembled at capping parameters from very low (aluminum crimp seal barely applied) to very high (possibly yielding stress cracks in the vial neck area). These samples are subsequently assessed for % compression of the stopper and residual seal force (RSF), an indirect measure of the amount of force the stopper is applying to the land-seal of the vial. The third, and most critical part of the triad, is helium leak testing. As each set of samples undergo helium leak testing, differences in leak performance between the sets can be identified. An ideal set of capping parameters that correlates to consistently low leak rates can be determined. Additionally, an ideal residual seal force range can be identified.

The correlations between capping parameters, RSF, and helium leak rate can be immensely valuable. For example, this work can be performed at lab-scale for development purposes, helping to inform final settings for a manufacturing setting. Manufacturing capping settings can be tailored to yield package RSF data in line with laboratory results. Package systems produced on that full-scale line can be further tested by helium leak detection as final confirmation and as part of a complete assembly validation for the product-package system and its assembly processes.

To further provide insight into the value of this approach, if product is being manufactured at 3 sites, the identified capping settings can be employed at each site, aiding in the transfer and validation process. More importantly, samples can be pulled from the line at each site and routinely checked by RSF. If the samples pulled off the line exhibit RSF values within a range that correlates to reduced risk of leakage and consistent with historical data, capping processes are likely under control. Although this does not guarantee package integrity, it provides an added layer of control, and can be referred to as an ongoing seal quality test. Similarly, helum leak detection can be employed on a routine basis for additional confidence, as helium would be considered a true seal integrity test.

Numerous capping optimization and assembly validation studies like these have been performed using LDA SIMS 1284+ helium leak detector and LDA’s unique range of accessories for the pharmaceutical and medical device industries. As the concept of CCI, and inherent CCI specifically, continues to be a topic regulatory agencies are more interested in, it is likely this trend of evaluating CCI in package development and validation will become an expectation. However, this change is one that should be welcomed by industry. Evaluating components prior to their use potentially prevents costly component changes down the road, and can lead to safer, less recall-prone packaging.

package integrity verification, CCI program, container closure integrity testing
Nov 2020

2019 PDA Container Closure Integrity Testing Workshop Presentation

2019 PDA Container Closure Integrity Testing Workshop Presentation

Presentation Summary

At the 2019 PDA Container Closure Integrity Testing Workshop in Gothenburg, Sweden, the following presentation was given as a 20 minute introduction to the use of helium leak detection for container closure integrity testing (CCIT).

Presented on behalf of Leak Detection Associates, the world’s premier manufacturer of custom-built helium leak detection solutions for pharmaceutical, biotechnology, medical device and food packaging clients, the presentation seeks to impart reviewers with an overview understanding of helium leak detection principles of operation, realistic methods for application to pharmaceutical packaging, and case study applications.

Helium gas is a small, nonreactive molecule, making it an ideal tracer for leakage testing, as employed by LDA’s SIMS 1915+ Helium Leak Detector. However, when it comes to preparing samples and subjecting them to a test, there are a range of approaches, each with respective ideal use cases. This presentation aims to illustrate some of the more common ways in which helium leak testing is applied to pharmaceutical packaging such as blisters, vials, and syringes. Reviewed approaches include the sniffer test, filling samples with helium prior to sealing, post-seal helium fill, using LDA’s proprietary vial filler and HSAM, and continuous fill using unique fixtures. Test approaches with reference to ASTM F2391 are discussed.

Important to the message of the presentation are the two case applications presented. The first discusses the application of helium leak testing to vial capping optimization, or assembly validation. In the second case application, an approach for evaluating individual ribs of a plunger is proposed. This type of approach is beneficial to those evaluating inherent integrity or defining their sterile barrier, which has implications for plunger movement during transit. This concept is becoming increasingly relevant as the expansion of prefilled syringe and cartridge-based delivery systems continues.

use of helium leak detection for ccit, container closure integrity testing, ccit
May 2020

Leak Detection Associates to Serve as Technical Presenter at PDA Europe CCIT Training Course

Leak Detection Associates to Serve as Technical Presenter at PDA Europe CCIT Training Course


Download Presetation – 2020 PDA Container Closure Integrity Workshop

Leak Detection Associates, the leading global supplier of helium based leak detection systems for the Pharmaceutical, Biotechnology and Medical Device Industries, is excited to announce that it will be a contributing instrument manufacturer and technical presenter at the Parenteral Drug Association (PDA) Container Closure Integrity Testing Basic Training Course. Held in conjunction with PDA Europe’s 10th Parenteral Packaging Conference, the two-day training program encompasses presentations on theory and real-life applications of all deterministic container closure integrity test (CCIT) technologies referenced in USP 1207. Critically, participating attendees are given the opportunity to witness demonstrations of actual instrumentation, with the unique opportunity for hands-on use in an engaging and learning-based environment.

The PDA 10th Parenteral Packaging Conference will be held in Basel, Switzerland on February 25th & 26th and the CCI specific training course is scheduled to follow on February 26th & 27th. Presenting on behalf of Leak Detection Associates will be Brian Mulhall, CEO and former Founder/President of Whitehouse Analytical Laboratories, while Jeff Morrow Lucas, LDA’s Director of Engineering, will host the hands-on technical training for attendees. In support of these technical presentations and hands-on activities, Leak Detection Associates will be providing its newest model, the SIMS 1915+ Helium Leak Detection System. Attendees will gain an understanding of how the system can be used to establish inherent integrity, optimize manufacturing, and more for a range of package systems and at extreme levels of sensitivity. LDA will also be featuring its new, low temperature add-on system that enables analysis of packages down to -80°C, critical for product-packages stored at these aggressive temperatures.

“We are extremely excited to be part of this highly educational event to specifically represent a key test method for container and package integrity testing specific to USP 1207 requirements,” commented Brian Mulhall, LDA’s CEO. “For more than 20 years, Leak Detection Associates has held a leadership role in the development and use of helium technology for container leak testing and having the opportunity to advance our knowledge and experience as part of a unique training seminar such as this will enable the value of helium leak testing to be shared with many relevant participants who are looking for CCI solutions in this highly regulated area.”

This course focuses on theoretical and practical fundamentals of various CCI testing technologies and provides a systematic approach to apply these testing methods for CCI verification throughout drug product lifecycles. The course, as a whole, will enable the participants to implement CCI testing strategies to ensure adequate drug product protection and be compliant with relevant regulatory and compendial requirements. In this course, participants gain critical problem-solving skills through:

  • Interactive discussions with a panel of cross-functional technical experts consisting of CCI testing laboratory experts, testing instrument suppliers/manufacturers, and pharmaceutical packaging development engineers
  • Hands-on testing training on the newest innovations and state-of-the-art instruments
  • Real-world case studies

Being held in conjunction with the 10th Parenteral Packaging Conference, this training course will utilize lectures, case studies, and interactive hands-on training on testing instruments to provide insight into the latest developments of Container Closure Integrity (CCI) Testing. It is expected that participants will develop an understanding of the most up-to-date regulatory and pharmacopeia requirements on CCIT while learning how to define CCI requirements for various container and drug product types using a risk-based approach. The key focus will be on practical applications using the deterministic methods such as tracer gas detection (e.g. helium leak detection), electrical conductivity and capacitance (HVLD), vacuum decay leak detection, laser-based gas headspace analysis, and mass extraction leak tests. Other key topic areas to be covered include selecting and applying appropriate testing methods for both laboratory and in-process testing to formulate comprehensive package integrity verification profiles, defining CCI testing method development and validation approaches and best practices, and avoiding common issues and pitfalls in CCI testing applications. To learn more about the conference and to register for attendance at this valuable training course, please visit http://www.pda.org.


Parenteral Packaging Conference, Container Closure Integrity Testing, SIMS 1915+ Helium Leak Detection System

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