Skip to main content

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

References

  1. 1.↵
    U.S. Pharmacopeial Convention, General Chapter 〈1207.1〉 Package Integrity Testing in the Product Life Cycle—Test Method Selection and Validation. In USP 43—NF 38, USP: Rockville, MD, 2020.
  2. 2.↵
    1. Morton D. K.
    Container/Closure Integrity of Parenteral Vials. J. Parenter. Sci. Technol. 1987, 41 (5), 145–158.
    OpenUrlPubMed
  3. 3.↵
    1. Kirsch L. E.,
    2. Nguyen L.,
    3. Moeckly C. S.,
    4. Gerth R.
    Pharmaceutical Container/Closure Integrity II. The Relationship Between Microbial Ingress and Helium Leak Rates in Rubber-Stoppered Glass Vials. PDA J. Pharm. Sci. Technol. 1997, 51 (5), 195–202.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Morrical B. D.,
    2. Goverde M.,
    3. Grausse J.,
    4. Gerwig T.,
    5. Vorgrimler L.,
    6. Morgen R.,
    7. Büttiker J.-P.
    Leak Testing in Parenteral Packaging: Establishment of Direct Correlation Between Helium Leak Rate Measurements and Microbial Ingress for Two Different Leak Types. PDA J. Pharm. Sci. Technol. 2007, 61 (4), 226–236.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Sudo H.,
    2. O'driscoll M.,
    3. Nishiwaki K.,
    4. Kawamoto Y.,
    5. Gammell P.,
    6. Schramm G.,
    7. Wertli T.,
    8. Prinz H.,
    9. Mori A.,
    10. Sako K.
    Development of a Nondestructive Leak Testing Method Utilizing the Head Space Analyzer for Ampoule Products Containing Ethanol-Based Solutions. PDA J. Pharm. Sci. Technol. 2012, 66 (5), 434–444.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Zuleger B.,
    2. Werner U.,
    3. Kort A.,
    4. Glowienka R.,
    5. Wehnes E.,
    6. Duncan D.
    Container/Closure Integrity Testing and the Identification of a Suitable Vial/Stopper Combination for Low-Temperature Storage at −80°C. PDA J. Pharm. Sci. Technol. 2012, 66 (5), 453–465.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Caudill A. A.,
    2. Victor K.,
    3. Timmins M.,
    4. Veale J.
    Container Closure Integrity Test Using Frequency Modulation Spectroscopy Headspace Analysis with Carbon Dioxide as a Tracer Gas. PDA J. Pharm. Sci. Technol. 2021, 75 (2), 157–172.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Victor K.,
    2. Caudill A. A.,
    3. Veale J.
    Container Closure Integrity Test Method Development on Vials Stored at −80°C Using Headspace Carbon Dioxide Analysis. PDA J. Pharm. Sci. Technol. 2022, 76 (5), 395–415.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Nier A. O.,
    2. Stevens C. M.,
    3. Hustrulid A.,
    4. Abbott T. A.
    Mass Spectrometer for Leak Detection. J. Appl. Phys. 1947, 18 (1), 30–33.
    OpenUrl
  10. 10.↵
    1. Brown H.,
    2. Mahler H.-C.,
    3. Mellman J.,
    4. Nieto A.,
    5. Wagner D.,
    6. Schaar M.,
    7. Mathaes R.,
    8. Kossinna J.,
    9. Schmitting F.,
    10. Dreher S.,
    11. Roehl H.,
    12. Hemminger M.,
    13. Wuchner K.
    Container Closure Integrity Testing—Practical Aspects and Approaches in the Pharmaceutical Industry. PDA J. Pharm. Sci. Technol. 2017, 71 (2), 147–162.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Mathaes R.,
    2. Wuchner K.,
    3. Riesop D.,
    4. Wagner D.,
    5. Dreher S.,
    6. Woelfle F.,
    7. Mudumala P. R.,
    8. Bonvin D.,
    9. Müller C.,
    10. Traub-Hoffmann K.,
    11. Hebting H.
    A Multicompany Survey Study for Helium Leak Container Closure Integrity Test. PDA J. Pharm. Sci. Technol. 2022, 76 (3), 216–235.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Bjorklund G. C.
    Frequency-Modulation Spectroscopy: A New Method for Measuring Weak Absorptions and Dispersions. Opt. Lett. 1980, 5 (1), 15–17.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Riris H.,
    2. Carlisle C. B.,
    3. Carr L. W.,
    4. Cooper D. E.,
    5. Martinelli R. U.,
    6. Menna R. J.
    Design of an Open Path Near-Infrared Diode Laser Sensor: Application to Oxygen, Water, and Carbon Dioxide Vapor Detection. Appl. Opt. 1994, 33 (30), 7059–7066.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Lin T. P.,
    2. Hsu C. C.
    Determination of Residual Moisture in Lyophilized Protein Pharmaceuticals Using a Rapid and Non-Invasive Method: Near Infrared Spectroscopy. PDA J. Pharm. Sci. Technol. 2002, 56 (4), 196–205.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Lin T. P.,
    2. Hsu C. C.,
    3. Kabakoff B. D.,
    4. Patapoff T. W.
    Application of Frequency-Modulated Spectroscopy in Vacuum Seal Integrity Testing of Lyophilized Biological Products. PDA J. Pharm. Sci. Technol. 2004, 58 (2), 106–115.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Lysfjord J.
    1. Veale J.
    New Inspection Techniques for Aseptic Processing. In Practical Aseptic Processing: Fill and Finish; Lysfjord J., Ed.; PDA: Bethesda, MD, 2009; Vol. 1.
  17. 17.↵
    1. Templeton A. C.,
    2. Han Y.-H. R.,
    3. Mahajan R.,
    4. Chern R. T.,
    5. Reed R.
    Rapid Headspace Oxygen Analysis for Pharmaceutical Packaging Applications. Pharm. Technol. 2002, 26, 44–61.
    OpenUrl
  18. 18.↵
    1. Duncan D.,
    2. Cundell T.,
    3. Levac L.,
    4. Veale J.,
    5. Kuiper S.,
    6. Rao R.
    The Application of Noninvasive Headspace Analysis to Media Fill Inspection. PDA J. Pharm. Sci. Technol. 2016, 70 (3), 230–247.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Nieto A.,
    2. Roehl H.,
    3. Brown H.,
    4. Nikoloff J.,
    5. Adler M.,
    6. Mahler H.-C.
    Evaluation of Container Closure System Integrity for Frozen Storage Drug Products. PDA J. Pharm. Sci. Technol. 2016, 70 (2), 120–133.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Hede J. O.,
    2. Fosbøl P. L.,
    3. Berg S. W.,
    4. Dahl S.
    Container Closure Integrity Testing—Method Development for Freeze-Dried Products Using Laser-Based Headspace Oxygen Analysis. PDA J. Pharm. Sci. Technol. 2019, 73 (2), 170–180.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Morton D. K.,
    2. Lordi N. G.,
    3. Ambrosio T. J.
    Quantitative and Mechanistic Measurements of Parenteral Vial Container/Closure Integrity. Leakage Quantitation. J. Parenter. Sci. Technol. 1989, 43 (2), 88–97.
    OpenUrlPubMed
  22. 22.↵
    1. Nguyen L. T.,
    2. Muangsiri W.,
    3. Schiere R.,
    4. Guazzo D. K.,
    5. Kirsch L. E.
    Pharmaceutical Container/Closure Integrity IV: Development of an Indirect Correlation Between Vacuum Decay Leak Measurement and Microbial Ingress. PDA J. Pharm. Sci. Technol. 1999, 53 (4), 211–216.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Kirsch L. E.
    Pharmaceutical Container/Closure Integrity VI: A Report on the Utility of Liquid Tracer Methods for Evaluating the Microbial Barrier Properties of Pharmaceutical Packaging. PDA J. Pharm. Sci. Technol. 2000, 54 (4), 305–314.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Gehrmann M. R.,
    2. Mcandrew T. P.
    Long-Term Study of Container Closure Integrity of Rubber–Glass Vial Systems by Multiple Methods. PDA J. Pharm. Sci. Technol. 2020, 74 (1), 147–161.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Wolf H.,
    2. Stauffer T.,
    3. Chen S.-C. Y.,
    4. Lee Y.,
    5. Forster R.,
    6. Ludzinski M.,
    7. Kamat M.,
    8. Mulhall B.,
    9. Guazzo D. M.
    Vacuum Decay Container/Closure Integrity Testing Technology. Part 2. Comparison to Dye Ingress Tests. PDA J. Pharm. Sci. Technol. 2009, 63 (5), 489–498.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Simonetti A.,
    2. Amari F.
    Non-Destructive Vacuum Decay Method for Pre-Filled Syringe Closure Integrity Testing Compared with Dye Ingress Testing and High-Voltage Leak Detection. PDA J. Pharm. Sci. Technol. 2015, 69 (1), 108–122.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Peláez S. S.,
    2. Mahler H.-C.,
    3. Herdlitschka C.,
    4. Wertli T.,
    5. Kahl M.,
    6. Koulov A.,
    7. Matter A.,
    8. Singh S. K.,
    9. Widmer M.,
    10. Germershaus O.,
    11. Mathaes R.
    Comparing Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies. PDA J. Pharm. Sci. Technol. 2019, 73 (3), 220–234.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Huon C.,
    2. Tiwari A.,
    3. Rotella C.,
    4. Mangiagalli P.,
    5. Persson B. N. J.
    Air, Helium and Water Leakage in Rubber O-Ring Seals with Application to Syringes. Tribol. Lett. 2022, 70 (2), 35.
    OpenUrl
  29. 29.↵
    1. Victor K. G.,
    2. Levac L.,
    3. Timmins M.,
    4. Veale J.
    Method Development for Container Closure Integrity Evaluation via Headspace Gas Ingress by Using Frequency Modulation Spectroscopy. PDA J. Pharm. Sci. Technol. 2017, 71 (6), 429–453.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    European Commission. EudraLex—The Rules Governing Medicinal Products in the European Union, Volume 4: Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 1: Manufacture of Sterile Medicinal Products. European Commission: Brussels, 2022
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
Sign In to Email Alerts with your Email Address
Email 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.
8 + 2 =
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
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
  • Facebook Like
  • Google Plus One

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

  • Analysis of Virus Clearance for Biotechnology Manufacturing Processes from Early to Late Phase Development
  • Coring and Fragmentation of Elastomeric Needle Shield in a Pre-Filled Syringe
  • Worldwide Regulatory Reliance: Results of an Executed Chemistry, Manufacturing, and Control Post-Approval Change Pilot
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