Skip to main content
  • Main menu
  • User menu
  • Search

Main menu

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
PDA Journal of Pharmaceutical Science and Technology
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
PDA Journal of Pharmaceutical Science and Technology

Advanced Search

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • Follow pda on Twitter
  • Visit PDA on LinkedIn
  • Visit pda on Facebook
Research ArticleResearch

Comparing Container Closure Integrity Test Methods—Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls

Christian Proff, Ken Victor, Allison Alix Caudill, Jirakan Nunkaew, Gemma AlmatÓ Bellavista, Holger RÖhl and James Veale
PDA Journal of Pharmaceutical Science and Technology November 2024, 78 (6) 681-698; DOI: https://doi.org/10.5731/pdajpst.2023.012881
Christian Proff
1F. Hoffmann-La Roche Ltd, Global Device and Packaging Development, PTDZ, 4070 Basel, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: christian.proff@roche.com
Ken Victor
2Lighthouse Instruments, LLC., Charlottesville, VA 22902
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allison Alix Caudill
2Lighthouse Instruments, LLC., Charlottesville, VA 22902
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jirakan Nunkaew
2Lighthouse Instruments, LLC., Charlottesville, VA 22902
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gemma AlmatÓ Bellavista
1F. Hoffmann-La Roche Ltd, Global Device and Packaging Development, PTDZ, 4070 Basel, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Holger RÖhl
1F. Hoffmann-La Roche Ltd, Global Device and Packaging Development, PTDZ, 4070 Basel, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Veale
2Lighthouse Instruments, LLC., Charlottesville, VA 22902
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

As described in USP <1207>, the deterministic leak test methods using laser-based gas headspace analysis and helium leakage are those with the highest sensitivities. As stated in the chapter, “no single package leak test or package seal quality test method is applicable to all product-package systems”; therefore, knowing the advantages and disadvantages of both of these techniques, and the extent to which they can be substituted for each other, is valuable. In an effort to begin addressing this issue, a systematic study using these two techniques has been performed. This study used the same well-defined positive controls prepared with microcapillaries for both measurement techniques. For the headspace gas analysis technique, the headspace carbon dioxide content was measured at multiple time points during three separate conditioning cycles using either a 0.5, 1.0, or 2.0 bar CO2 overpressure; the observed change in headspace carbon dioxide was then used to determine an ingress rate for each positive control. For the helium leakage technique, the positive controls were measured with a standard helium leak detector with 100% helium atmosphere on the atmospheric pressure side of the artificial defects. The resulting leakage rates from both techniques were compared for ingress into both ISO 2 R and ISO 10 R vials. The obtained correlation between helium and carbon dioxide leakage rates resulted in a minimum R2 coefficient of 0.98 across all 12 runs. Additionally, both setups met the acceptance criteria for accuracy with their respective calibrated standards.

  • Container closure integrity
  • USP
  • <1207>
  • Headspace gas analysis
  • Helium leakage
  • Frequency modulation spectroscopy
  • Carbon dioxide
  • © PDA, Inc. 2024
View Full Text

PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.  

If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing. 

Full issue PDFs are for PDA members only.

Note to pda.org users

The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

patientACCESS

patientACCESS - Patients desiring access to articles

Full issue PDFs are for PDA members only. You can join PDA at www.pda.org. 

PreviousNext
Back to top

In This Issue

PDA Journal of Pharmaceutical Science and Technology: 78 (6)
PDA Journal of Pharmaceutical Science and Technology
Vol. 78, Issue 6
November/December 2024
  • Table of Contents
  • Index by Author
  • Complete Issue (PDF)
Print
Download PDF
Article Alerts
Email Article
Citation Tools
Share
Comparing Container Closure Integrity Test Methods—Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
Christian Proff, Ken Victor, Allison Alix Caudill, Jirakan Nunkaew, Gemma AlmatÓ Bellavista, Holger RÖhl, James Veale
PDA Journal of Pharmaceutical Science and Technology Nov 2024, 78 (6) 681-698; DOI: 10.5731/pdajpst.2023.012881
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget

Jump to section

  • Article
    • Abstract
    • Introduction
    • 2. Materials and Methods
    • 3. Results/Discussion
    • 4. Conclusions
    • Author Contributions
    • Conflict of Interest Declaration
    • References
  • Figures & Data
  • References
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Quantitative and Qualitative Evaluation of Microorganism Profile Identified in Bioburden Analysis in a Biopharmaceutical Facility in Brazil: Criteria for Classification and Management of Results
  • Evaluation of Extreme Depyrogenation Conditions on the Surface Hydrolytic Resistance of Glass Containers for Pharmaceutical Use
  • A Holistic Approach for Filling Volume Variability Evaluation and Control with Statistical Tool
Show more Research

Similar Articles

Keywords

  • Container closure integrity
  • USP
  • <1207>
  • Headspace gas analysis
  • Helium leakage
  • Frequency modulation spectroscopy
  • Carbon dioxide

Readers

  • About
  • Table of Content Alerts/Other Alerts
  • Subscriptions
  • Terms of Use
  • Contact Editors

Author/Reviewer Information

  • Author Resources
  • Submit Manuscript
  • Reviewers
  • Contact Editors

Parenteral Drug Association, Inc.

  • About
  • Advertising/Sponsorships
  • Events
  • PDA Bookstore
  • Press Releases

© 2025 PDA Journal of Pharmaceutical Science and Technology Print ISSN: 1079-7440  Digital ISSN: 1948-2124

Powered by HighWire
Alerts for this Article
Sign In to Email Alerts with your Email Address
Email this Article

Thank you for your interest in spreading the word on PDA Journal of Pharmaceutical Science and Technology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Comparing Container Closure Integrity Test Methods—Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
(Your Name) has sent you a message from PDA Journal of Pharmaceutical Science and Technology
(Your Name) thought you would like to see the PDA Journal of Pharmaceutical Science and Technology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Comparing Container Closure Integrity Test Methods—Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
Christian Proff, Ken Victor, Allison Alix Caudill, Jirakan Nunkaew, Gemma AlmatÓ Bellavista, Holger RÖhl, James Veale
PDA Journal of Pharmaceutical Science and Technology Nov 2024, 78 (6) 681-698; DOI: 10.5731/pdajpst.2023.012881

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

We use cookies on this site to enhance your user experience

By clicking any link on this page you are giving your consent for us to set cookies.