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 Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies

Sarah S. Peláez, Hanns-Christian Mahler, Christoph Herdlitschka, Toni Wertli, Matthias Kahl, Atanas Koulov, Anja Matter, Satish K. Singh, Martina Widmer, Oliver Germershaus and Roman Mathaes
PDA Journal of Pharmaceutical Science and Technology May 2019, 73 (3) 220-234; DOI: https://doi.org/10.5731/pdajpst.2018.009332
Sarah S. Peláez
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hanns-Christian Mahler
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christoph Herdlitschka
2Wilco AG, Wohlen, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toni Wertli
2Wilco AG, Wohlen, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Kahl
2Wilco AG, Wohlen, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Atanas Koulov
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anja Matter
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satish K. Singh
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martina Widmer
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver Germershaus
3Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roman Mathaes
1Lonza Drug Product Services, Basel, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: roman.mathaes@lonza.com
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

References

  1. 1.↵
    U.S. Pharmacopeial Convention, General Chapter <1207> Package Integrity Evaluation - Sterile Products. In USP 39-NF 34, USP: Rockville, MD, 2016; pp 1700–1707.
  2. 2.↵
    1. Mahler H. C.,
    2. Friess W.,
    3. Grauschopf U,
    4. Kiese S.
    Protein aggregation: pathways, induction factors and analysis. J. Pharm. Sci. 2009, 98 (9), 2909–2934.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Pikal M. J.,
    2. Dellerman K.,
    3. Roy M. L.
    Formulation and stability of freeze-dried proteins: effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone. Dev. Biol. Stand. 1992, 74, 21–37; discussion 37–38.
    OpenUrlPubMed
  4. 4.↵
    European Commission, EudraLex-The Rules Governing Medicinal Products in the European Union, Volume 4: EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1: Manufacture of Sterile Medicinal Products. European Commission: Brussels, 2008.
  5. 5.↵
    U.S. Pharmacopeial Convention, General Chapter <1207.1> Package Integrity Testing in the Product Life Cycle -Test Method Selection and Validation. In USP 39–NF 34, USP: Rockville, MD, 2016; pp 1707–1719.
  6. 6.↵
    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
  7. 7.↵
    1. Kolhe P.,
    2. Shah M.,
    3. Rathore N.
    1. Li L.
    Advances in Container Closure Integrity Testing. In Sterile Product Development: Formulation, Process, Quality and Regulatory Considerations, Kolhe P., Shah M., Rathore N., Eds. Springer: New York, 2013; pp 315–329.
  8. 8.↵
    1. Burrell L. S.,
    2. Carver M. W.,
    3. DeMuth G. E.,
    4. Lambert W. J.
    Development of a Dye Ingress Method to Assess Container-Closure Integrity: Correlation to Microbial Ingress. PDA J. Pharm. Sci. Technol. 2000, 54 (6), 449–455.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Wolf H.,
    2. Stauffer T.,
    3. Chen S. C.,
    4. Lee Y.,
    5. Forster R.,
    6. Ludzinski M.,
    7. Kamat M.,
    8. Godorov P.,
    9. Guazzo D. M.
    Vacuum decay container/closure integrity testing technology. Part 1. ASTM F2338–09 precision and bias studies. PDA J. Pharm. Sci. Technol. 2009, 63 (5), 472–488.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    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
  11. 11.↵
    1. Veale J. R.,
    2. Victor K. G.
    Oxygen Permeation Rates Through Syringe Components; Lighthouse Instruments, LLC: Charlottesville, VA, Published Online Nov 28, 2016: https://biopharma-asia.com/technical-papers/oxygen-permeation-rates-through-syringe-components/ (accessed November 10, 2017).
  12. 12.↵
    1. Wertli A.
    Method for leak testing closed, at least partially gas filled containers. EP2449356A1/US9891132B2, 2018.
  13. 13.↵
    1. Kirsch L. E.,
    2. Nguyen L.,
    3. Moeckly C. S.
    Pharmaceutical container/closure integrity. I: Mass spectrometry-based helium leak rate detection for rubber-stoppered glass vials. PDA J. Pharm. Sci. Technol. 1997, 51 (5), 187–194.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Morrical B. D.,
    2. Goverde M.,
    3. Grausse J.,
    4. Gerwig T.,
    5. Vorgrimler L.,
    6. Morgen R.,
    7. Buttiker 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
  15. 15.↵
    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
  16. 16.↵
    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
  17. 17.↵
    1. Keller S. W.
    Determination of the leak size critical to package sterility maintenance. Ph.D Dissertation, Virginia Polytechnic Institute and State University, 1998. Available from https://vtechworks.lib.vt.edu/handle/10919/26690 (accessed July 14, 2018).
  18. 18.↵
    1. Yoon S. Y.,
    2. Sagi H.,
    3. Goldhammer C.,
    4. Li L.
    Mass extraction container closure integrity physical testing method development for parenteral container closure systems. PDA J. Pharm. Sci. Technol. 2012, 66 (5), 403–419.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Wolf H.,
    2. Stauffer T.,
    3. Chen S. C.,
    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
  20. 20.↵
    1. Nieto A.,
    2. Roehl H.,
    3. Brown H.,
    4. Adler M.,
    5. Chalus P.,
    6. Mahler H. C.
    Artificial Leaks in Container Closure Integrity Testing: Nonlinear Finite Element Simulation of Aperture Size Originated by a Copper Wire Sandwiched between the Stopper and the Glass Vial. PDA J. Pharm. Sci. Technol. 2016, 70 (4), 313–324.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Mathaes R.,
    2. Mahler H. C.,
    3. Roggo Y.,
    4. Ovadia R.,
    5. Lam P.,
    6. Stauch O.,
    7. Vogt M.,
    8. Roehl H.,
    9. Huwyler J.,
    10. Mohl S.,
    11. Streubel A.
    Impact of Vial Capping on Residual Seal Force and Container Closure Integrity. PDA J. Pharm. Sci. Technol. 2016, 70 (1), 12–29.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Gooch J. W.
    1. Gooch J. W.
    Hagen-Poiseuille Equation. In Encyclopedic Dictionary of Polymers, Gooch J. W., Ed.; Springer: New York, 2011; p 355.
  23. 23.↵
    1. Bialous A. J.,
    2. Peters P. H.,
    3. Stone E. E.
    Leakage Testing Handbook (revised edition) [Online]; National Aeronautics and Space Administration: Pasadena, CA, 1969; Vol. 952. https://archive.org/stream/nasa_techdoc_19690029458/19690029458_djvu.txt (accessed November 10, 2017).
  24. 24.
    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
  25. 25.↵
    1. Peláez S. S.,
    2. Mahler H. C.,
    3. Matter A.,
    4. Koulov A.,
    5. Singh S. K.,
    6. Germershaus O.,
    7. Mathaes R.
    Container Closure Integrity Testing of Prefilled Syringes. J. Pharm. Sci. 2018, 107 (8), 2091–2097.
    OpenUrl
  26. 26.↵
    1. Badkar A.,
    2. Wolf A.,
    3. Bohack L.,
    4. Kolhe P.
    Development of biotechnology products in pre-filled syringes: Technical considerations and approaches. AAPS PharmSciTech 2011, 12 (2), 564–572.
    OpenUrlPubMed
PreviousNext
Back to top

In This Issue

PDA Journal of Pharmaceutical Science and Technology: 73 (3)
PDA Journal of Pharmaceutical Science and Technology
Vol. 73, Issue 3
May/June 2019
  • Table of Contents
  • Index by Author
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 Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies
(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.
9 + 4 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Comparing Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies
Sarah S. Peláez, Hanns-Christian Mahler, Christoph Herdlitschka, Toni Wertli, Matthias Kahl, Atanas Koulov, Anja Matter, Satish K. Singh, Martina Widmer, Oliver Germershaus, Roman Mathaes
PDA Journal of Pharmaceutical Science and Technology May 2019, 73 (3) 220-234; DOI: 10.5731/pdajpst.2018.009332

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Comparing Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies
Sarah S. Peláez, Hanns-Christian Mahler, Christoph Herdlitschka, Toni Wertli, Matthias Kahl, Atanas Koulov, Anja Matter, Satish K. Singh, Martina Widmer, Oliver Germershaus, Roman Mathaes
PDA Journal of Pharmaceutical Science and Technology May 2019, 73 (3) 220-234; DOI: 10.5731/pdajpst.2018.009332
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Conclusion
    • Conflict of Interest Declaration
    • Abbreviations
    • References
  • Figures & Data
  • References
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Comparing Container Closure Integrity Test Methods--Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
  • A Multicompany Survey Study for Helium Leak Container Closure Integrity Test
  • Container Closure Integrity Test Using Frequency Modulation Spectroscopy Headspace Analysis with Carbon Dioxide as a Tracer Gas
  • 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 testing
  • Artificial leaks
  • Primary packaging
  • USP <1207>
  • Mass spectrometry-based helium leak detection
  • Laser-based headspace analysis

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