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Container Closure Integrity

Integrity of the closure of a drug product container/delivery systems is crucial to guarantee safety and efficacy. Methods (deterministic and probabilistic) to measure this have recently been set forth in USP Chapter 1207. This section presents papers discussing methods (e.g., helium leak, gas headspace, high-voltage leak detection) and their application to various systems.

When Glass Vials Fail At Low Temperatures, Consider A Cyclic Olefin Polymer System. 
W. Winters.  Pharmaceutical Online (July 25, 2017)


This article describes the many benefits of Daikyo Crystal Zenith® cyclic olefin polymer versus glass for low-temperature storage of drug products.

Link: https://www.pharmaceuticalonline.com/doc/when-glass-vials-fail-at-low-temperatures-consider-a-cyclic-olefin-polymer-system-0001?immediate=true

Container system for enabling commercial production of cryopreserved cell therapy products. 
E. Woods, et al.  Regen. Med., 5 (4), 659-667 (2010)


This article demonstrates that vials comprising Daikyo Crystal Zenith® cyclic olefin polymer are well-suited to cryogenic storage/transport of cell therapy products.

Link: https://www.ncbi.nlm.nih.gov/pubmed/20632866

Guidance for Industry -  Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products


This report discusses FDA thoughts on how both sterility testing and container closure integrity testing may be used to evaluate the performance of drug product packaging systems.

Link: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM146076.pdf

Non‐Destructive Container Closure Integrity Testing. 

H. Wolf (PTI Inspection Systems)


This presentation considers several different methods of measuring container closure integrity, and compares their relative utilities: (a) vacuum decay (loss of vacuum in evacuated chamber due to failure of container), dye ingress (visual observation of colorized fluid moving into container), ultrasonic (air pockets where container components join).

Link: https://www.pda.org/docs/default-source/website-document-library/chapters/presentations/new-england/non-destructive-container-closure-integrity-testing.pdf?sfvrsn=6

The Aseptic Core - Container Closure Integrity. 

Edward K. White.  Journal of Validation Technology (Spring 2012)


This review article considers various methods of container closure integrity testing for the major types of drug product containers (vials, syringes, IV bags) - in view of regulatory requirements.

Link: http://www.ivtnetwork.com/sites/default/files/IVTJVT0512_Aseptic_FInal.pdf

Introduction to Laser-Based Headspace Inspection and the Application to 100% Container Closure. 

D.I. Duncan and J.R. Veale (Lighthouse Instruments)


This article considers the fundamentals of gas headspace analysis for the measurement of container closure integrity – the physics of the process is described along with the types of containers for which it is suitable.

Link: http://www.lighthouseinstruments.com/uploads/New_documents_9Jan2015/Brochure_Whitepaper_2015_PRINT.pdf

Evaluating Package Integrity. 

H. Forcinio.  Pharmaceutical Technology, 39 (4) 76-77 (2015)


This article considers how changes to USP Chapter 1207 will affect the measurement of container closure integrity for drug product packaging systems.

Link: http://www.pharmtech.com/evaluating-package-integrity

Oxygen Permeation Rates Through Syringe Components. 

J.R. Veale and K.G. Victor (Lighthouse Instruments).  PDA Universe of Pre-filled Syringes & Injection Devices Conference (2016)


This poster considers the use of gas headspace analysis for the measurement of container closure integrity of syringes. The method can distinguish differences in gas permeability between plunger and tip, and between staked needle and Luer lock configurations.

Link: http://www.lighthouseinstruments.com/uploads/Job_Listings/Lighthouse_Poster_2016_PDA_Syringe-_Oxygen_Ingress.pdf









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