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

A New Integrated Modeling Approach with Case Studies for Gas Transmission of Container Closure Headspace

Qingyu Zeng
PDA Journal of Pharmaceutical Science and Technology September 2021, 75 (5) 394-406; DOI: https://doi.org/10.5731/pdajpst.2020.012351
Qingyu Zeng
West Pharmaceutical Services, Inc.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: qingyu.zeng@westpharma.com
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

This article presents a new theoretical integrated modeling approach for calculating container closure integrity (CCI) that concurrently accounts for both diffusion and mass/volumetric flow in real time; practical case studies are also presented. For pharmaceutical, biological, cell, and gene therapies, container closure systems (CCSs) must ensure drug sterility and stability by safeguarding against microbial contamination and gaseous ingress (e.g., oxygen, carbon dioxide, moisture) according to product requirements. In addition to the testing approach for evaluating CCI performance, a modeling approach can be an important part of a CCI control strategy. Modeling is a powerful tool that provides information in situations where testing is not feasible, technically impossible, too time-consuming, or too expensive. Previously published models have lacked a systematic approach or the versatility needed to coherently and concurrently integrate both diffusion and effusion to solve problems arising in field applications. The new integrated modeling approach described in this article applies a robust numerical method to real-world applications. The model is based on the law of conservation and continuity for molecular flow, Fick's law of diffusion, and the Darcy–Weisbach theory of frictional mass/volumetric flow. This new integrated modeling approach handles time-dependent diffusion and effusion by combining diffusion and mass/volumetric flow seamlessly in real time. For a CCS under vacuum filled with nitrogen, this new modeling approach is able to reveal that oxygen ingress into the CCS through a leak path will enter in two phases, starting with effusion and continuously followed by diffusion in a seamless transition. Our integrated modeling approach is able to calculate and capture the exact timing of the phase transition point, providing unique understanding of complicated CCS problems. Using the finite difference method, all modeling results are numerically solved from the governing equations along with initial and boundary conditions for each individual case. The modeling results were precise and consistent with previously published testing results. This new integrated modeling approach displayed its capability and versatility to handle complicated leakage scenarios in practical applications. As a part of CCI control strategy, the modeling approach is a powerful tool for evaluating leaks, gauging their leak sizes, determining whether the CCS conforms to product requirements, and making informed decisions accordingly. Although additional studies are to be carried out to fully develop the potential of this model, the applications hold great promise and in addition provide insight into CCI and may also provide a solid foundation for CCI testing method development and validation for CCI performance.

  • Container closure system (CCS)
  • Container closure integrity (CCI)
  • Diffusion
  • Mass and volumetric flow
  • Fick's law
  • Darcy–Weisbach equation
  • © PDA, Inc. 2021
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: 75 (5)
PDA Journal of Pharmaceutical Science and Technology
Vol. 75, Issue 5
September/October 2021
  • 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.
A New Integrated Modeling Approach with Case Studies for Gas Transmission of Container Closure Headspace
(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 + 0 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
A New Integrated Modeling Approach with Case Studies for Gas Transmission of Container Closure Headspace
Qingyu Zeng
PDA Journal of Pharmaceutical Science and Technology Sep 2021, 75 (5) 394-406; DOI: 10.5731/pdajpst.2020.012351

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
A New Integrated Modeling Approach with Case Studies for Gas Transmission of Container Closure Headspace
Qingyu Zeng
PDA Journal of Pharmaceutical Science and Technology Sep 2021, 75 (5) 394-406; DOI: 10.5731/pdajpst.2020.012351
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Methods—Formulation of the Integrated Modeling Framework
    • Results and Discussion
    • Summary
    • Conflict of Interest Declaration
    • Acknowledgments
    • References
  • Figures & Data
  • Info & Metrics
  • References
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Container Closure Integrity of Vial Primary Packaging Systems under Frozen Storage Conditions: A Case Study
  • Advances in Large Volume Subcutaneous Injections: A Pilot Tolerability Study of an Innovative Needle-Free Injection Platform
  • Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products
Show more Research

Similar Articles

Keywords

  • Container closure system (CCS)
  • Container closure integrity (CCI)
  • Diffusion
  • Mass and volumetric flow
  • Fick's law
  • Darcy–Weisbach equation

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

© 2023 PDA Journal of Pharmaceutical Science and Technology ISSN: 1079-7440

Powered by HighWire