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Research ArticleTechnology/Application

Mechanical Container Closure Integrity Test: A Method for Cartridge Systems

Michael W. Foubert, Benoit Lux, Julie Bourguard, Lucas Schultz, Meng John Zhao, Jason D. Marlin, Matthew S. Huser, Henri Hebting and Lei Li
PDA Journal of Pharmaceutical Science and Technology May 2025, 79 (3) 303-319; DOI: https://doi.org/10.5731/pdajpst.2024.012941
Michael W. Foubert
1Eli Lilly and Company, 1223 W Morris Street, Indianapolis, IN 46221;
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  • For correspondence: foubert_michael_william@lilly.com
Benoit Lux
2Eli Lilly and Company, 2 rue du Colonel Lilly, BP 70419 Fegersheim, 67412 Illkirch Cedex, France; and
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Julie Bourguard
2Eli Lilly and Company, 2 rue du Colonel Lilly, BP 70419 Fegersheim, 67412 Illkirch Cedex, France; and
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Lucas Schultz
2Eli Lilly and Company, 2 rue du Colonel Lilly, BP 70419 Fegersheim, 67412 Illkirch Cedex, France; and
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Meng John Zhao
1Eli Lilly and Company, 1223 W Morris Street, Indianapolis, IN 46221;
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Jason D. Marlin
3Eli Lilly and Company, 1555 S Harding Street, Indianapolis, IN 46221.
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Matthew S. Huser
1Eli Lilly and Company, 1223 W Morris Street, Indianapolis, IN 46221;
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Henri Hebting
2Eli Lilly and Company, 2 rue du Colonel Lilly, BP 70419 Fegersheim, 67412 Illkirch Cedex, France; and
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Lei Li
1Eli Lilly and Company, 1223 W Morris Street, Indianapolis, IN 46221;
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References

  1. 1.↵
    U.S. Pharmacopeial Convention, General Chapter <1207> Package Integrity Evaluation—Sterile Products. In USP 39—NF34 Supplement 1, USP: Rockville, MD, 2016.
  2. 2.↵
    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
  3. 3.↵
    1. Peláez S. S.,
    2. Mahler H.-C.,
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    5. Kahl M.,
    6. Koulov A.,
    7. Matter A.,
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    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
  4. 4.↵
    1. Duncan D.
    Container Closure Integrity Testing of Finished Sterile Injectable Product. Pharm. Technol. 2019, 43 (9), 38–41.
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  5. 5.↵
    1. Sacha G. A.,
    2. Saffell-Clemmer W.,
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    4. Akers M. J.
    Practical Fundamentals of Glass, Rubber, and Plastic Sterile Packaging Systems. Pharm. Dev. Technol. 2010, 15 (1), 6–34.
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  6. 6.↵
    U.S. Pharmacopeial Convention, General Chapter <660> Containers—Glass. In USP 46—NF41, USP: Rockville, MD, 2023.
  7. 7.↵
    ASTM International, ASTM FF2095-07 Standard Test Methods for Pressure Decay Leak Test for Flexible Packages With and Without Restraining Plates, ASTM: West Conshohocken, PA, 2013.
  8. 8.↵
    ASTM International, ASTM D6147-97 Standard Test Method for Vulcanized Rubber and Thermoplastic Elastomer—Determination of Force Decay (Stress Relaxation) in Compression, ASTM: West Conshohocken, PA, 2014.
  9. 9.↵
    International Organization for Standardization, ISO 3384-1:2019 Rubber, Vulcanized or Thermoplastic—Determination of Stress Relaxation in Compression—Part 1: Testing at Constant Temperature, ISO: Geneva, 2019.
  10. 10.↵
    International Organization for Standardization, ISO 11608-3:2012 Needle-Based Injection Systems for Medical Use—Requirements and Test Methods—Part 3: Finished Containers, ISO: Geneva, 2012.
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PDA Journal of Pharmaceutical Science and Technology: 79 (3)
PDA Journal of Pharmaceutical Science and Technology
Vol. 79, Issue 3
May/June 2025
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Mechanical Container Closure Integrity Test: A Method for Cartridge Systems
Michael W. Foubert, Benoit Lux, Julie Bourguard, Lucas Schultz, Meng John Zhao, Jason D. Marlin, Matthew S. Huser, Henri Hebting, Lei Li
PDA Journal of Pharmaceutical Science and Technology May 2025, 79 (3) 303-319; DOI: 10.5731/pdajpst.2024.012941

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Mechanical Container Closure Integrity Test: A Method for Cartridge Systems
Michael W. Foubert, Benoit Lux, Julie Bourguard, Lucas Schultz, Meng John Zhao, Jason D. Marlin, Matthew S. Huser, Henri Hebting, Lei Li
PDA Journal of Pharmaceutical Science and Technology May 2025, 79 (3) 303-319; DOI: 10.5731/pdajpst.2024.012941
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Keywords

  • Parenteral drugs
  • Sterility
  • Container-closure integrity
  • Mechanical container-closure integrity test
  • Force decay method
  • Constant force method
  • Force-to-leak test
  • Dye ingress test

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