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Research ArticleResearch

Single-Use System Integrity I: Using a Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL)

Saeedeh Aliaskarisohi, Marc Hogreve, Carole Langlois, Jonathan Cutting, Magali Barbaroux, Jean-Marc Cappia and Marie-Christine Menier
PDA Journal of Pharmaceutical Science and Technology September 2019, 73 (5) 459-469; DOI: https://doi.org/10.5731/pdajpst.2018.009688
Saeedeh Aliaskarisohi
1R&D, Sartorius Stedim Biotech GmbH, Goettingen, Germany;
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Marc Hogreve
1R&D, Sartorius Stedim Biotech GmbH, Goettingen, Germany;
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  • For correspondence: marc.hogreve@sartorius.com
Carole Langlois
2Sartorius Stedim Biotech FMT SAS, Aubagne, France; and
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Jonathan Cutting
3R&D, Sartorius Stedim Inc, Bohemia, NY
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Magali Barbaroux
2Sartorius Stedim Biotech FMT SAS, Aubagne, France; and
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Jean-Marc Cappia
2Sartorius Stedim Biotech FMT SAS, Aubagne, France; and
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Marie-Christine Menier
2Sartorius Stedim Biotech FMT SAS, Aubagne, France; and
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References

  1. 1.↵
    Council of Europe; Methods of Preparing Sterile Products. In European Pharmacopoeia (Ph. Eur.), 8th ed.; Council of Europe: Strasbourg, France, 2014; Chapter 5.1.1.
  2. 2.↵
    European Commission, Annex I-Manufacture of Sterile Medicinal Products. In EudraLex—The Rules Governing Medicinal Products in the European Union, Volume 4: Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use; European Commission: Brussels, Belgium, 2010.
  3. 3.↵
    U.S. Food and Drug Administration, Guidance for Industry: Container and Closure System Integrity Testing In Lieu of Sterility Testing As a Component of Stability Protocol for Sterile Products. U.S. Department of Health and Human Services: Rockville, MD, 2008.
  4. 4.↵
    1. Chen C.,
    2. Harte B.,
    3. Lai C.,
    4. Pestka J.,
    5. Henyon D.
    Assessment of Package Integrity Using a Spray Cabinet Technique. J. Food Prot. 1991, 54 (8), 643–675.
    OpenUrl
  5. 5.↵
    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
  6. 6.↵
    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
  7. 7.↵
    1. Burell 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
  8. 8.↵
    1. Gilchrist J. E.,
    2. Rhea U. S.,
    3. Dickerson R. W.,
    4. Campbell J. E.
    Helium Leak Test for Micron-Sized Holes in Canned Foods. J. Food Prot. 1985, 48 (10), 856–860.
    OpenUrl
  9. 9.↵
    1. Bankes P.,
    2. Stringer M. F.
    The Design and Application of a Model System to Investigate Physical Factors Affecting Container Leakage. Int. J. Food Microbiol. 1988, 6 (4), 281–286.
    OpenUrlPubMed
  10. 10.↵
    1. Gilchrist J. E.,
    2. Shah D. B.,
    3. Radle D. C.,
    4. Dickerson R. W.
    Leak Detection in Flexible Retort Pouches. J. Food Prot. 1989, 52 (6), 412–415.
    OpenUrl
  11. 11.↵
    1. Keller S. W.,
    2. Marcy J. E.,
    3. Blakistone B. A.,
    4. Lacy G. H.,
    5. Hackney C. R.,
    6. Carter W. H.
    , Jr. Bioaerosol Exposure Method for Package Integrity Testing. J. Food Prot. 1996, 59 (7), 768–771.
    OpenUrl
  12. 12.↵
    1. Moghimi N.,
    2. Kim S.-J.,
    3. Park S.-I.
    Assessing of Flexible Packaging Integrity: Using the Aerosolization Bacteria. Packag. Technol. Sci. 2016, 29 (3), 135–143.
    OpenUrl
  13. 13.↵
    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
  14. 14.↵
    1. Pinckney M. B.,
    2. Luzzi L. A.,
    3. Needham T. E.
    , Jr. Resistance of Large-Volume Parenteral Containers to Forced Microbial Contamination. J. Pharm. Sci. 1973, 62 (1), 80–82.
    OpenUrlPubMed
  15. 15.↵
    1. Halls N. A.
    Achieving Sterility in Medical and Pharmaceutical Products, Marcel Dekker: New York, 1994.
  16. 16.↵
    1. Krebsbach T.,
    2. Schröder C.,
    3. Matthies C.
    Container Closure Integrity Test, Mikrobiologische Prüfung Der Integrität Von Primärverpackungen. Pharm. Ind. 2014, 76 (7), 1141–1147.
    OpenUrl
  17. 17.↵
    1. Guazzo D. M.
    Current Approaches in Leak Testing Pharmaceutical Packages. PDA J. Pharm. Sci. Technol. 1996, 50 (6), 378–385.
    OpenUrlFREE Full Text
  18. 18.↵
    1. Akers M.,
    2. Larrimore D.,
    3. Morton Guazzo D.
    Package Integrity Testing. In Parenteral Quality Control: Sterility, Pyrogen, Particulate and Package Integrity Testing; Informa Healthcare: New York, 2007, p 281.
  19. 19.↵
    1. Moghimi N.,
    2. Park S. I.
    Leakage Assessment of Flexible Pouches Using Dye Penetration Test with Correlation to Modeled Bacterial Aerosol Challenge Test. Food Sci. Biotechnol. 2017, 26 (4), 947–953.
    OpenUrl
  20. 20.↵
    1. Pethe V.,
    2. Dove M.,
    3. Terentiev A.
    Integrity Testing of Flexible Containers. BioPharm Int. 2011, 24 (11), 42–44.
    OpenUrl
  21. 21.↵
    1. Gibney M.
    Predicting Package Defects: Quantification of Critical Leak Size. Thesis; Virginia Polytechnic Institute and State University: Blacksburg, Virginia, 2000.
  22. 22.↵
    Dr. Erwin Post, Merz Group Services GmbH PDA Europe Conference on Pharmaceutical Microbiology, March 15–16, 2011 in Berlin, Germany. .
  23. 23.↵
    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
  24. 24.↵
    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
  25. 25.↵
    1. Hogreve M.,
    2. Langlois C.,
    3. Menier M. C.,
    4. Aliaskarisohi S.
    Ensuring the Integrity of Single-Use Containers, Providing Robustness, Science, and Helium-Based Technology with a Detection Limit of 2 μm. BioProcess Int. 2018, 16 (4), 54–59.
    OpenUrl
  26. 26.↵
    U.S. Pharmacopeial Convention. General Chapter <1207> Packaging Integrity Evaluation—Sterile Product. In USP–39 NF 34, USP, Rockville, MD, 2019.
  27. 27.↵
    1. Keller S.
    Determination of the Leak Size Critical to Package Sterility Maintenance. Ph.D. Dissertation, Virginia Polytechnic Institute and State University: Blacksburg, Virginia, 1998.
  28. 28.↵
    1. Pethe V.
    , Integrity Testing of Flexible Container Using the Helium Integrity Testing (HIT) Platform (2-D and 3-D Bags and Manifolds). http://downstreamcolumn.com/wp-content/uploads/sites/3/2013/06/Testing-of-Flexible-Containers-Using-the-HIT-Platform.pdf (accessed Jan 23, 2014).
  29. 29.↵
    Pharmaceutical Package Integrity, Technical Report No. 27. PDA J. Pharm. Sci. Technol. 1998, 52 (S2).
  30. 30.↵
    International Organization for Standardization. ISO 15747: Plastic Containers for Intravenous Injection. ISO: Geneva, Switzerland, 2003.
  31. 31.↵
    International Organization for Standardization. ISO 14644-1: 2015 Cleanrooms and associated controlled Environments—Part 1: Classification of air cleanliness by particle concentration. ISO: Geneva, Switzerland, 2015.
  32. 32.↵
    1. Keller S.,
    2. Marcy J.,
    3. Blakistone B.,
    4. Hackney C.,
    5. Carter W. H.,
    6. Lacy G.
    Effect of Microorganism Characteristics on Leak Size Critical to Predicting Package Sterility. Journal of Food Protection 2003, 66 (9), 1716–1719.
    OpenUrlPubMed
  33. 33.↵
    1. Denyer S. P.,
    2. Baird R. M.
    1. Kirsch L. E.
    Package Integrity Testing. In Guide to Microbiological Control in Pharmaceuticals and Medical Devices, 2nd ed.; Denyer S. P., Baird R. M., Eds.; CRC Press: Boca Raton, FL, 2007; Chapter 16, pp 367–381.
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PDA Journal of Pharmaceutical Science and Technology: 73 (5)
PDA Journal of Pharmaceutical Science and Technology
Vol. 73, Issue 5
September/October 2019
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Single-Use System Integrity I: Using a Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL)
Saeedeh Aliaskarisohi, Marc Hogreve, Carole Langlois, Jonathan Cutting, Magali Barbaroux, Jean-Marc Cappia, Marie-Christine Menier
PDA Journal of Pharmaceutical Science and Technology Sep 2019, 73 (5) 459-469; DOI: 10.5731/pdajpst.2018.009688

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Single-Use System Integrity I: Using a Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL)
Saeedeh Aliaskarisohi, Marc Hogreve, Carole Langlois, Jonathan Cutting, Magali Barbaroux, Jean-Marc Cappia, Marie-Christine Menier
PDA Journal of Pharmaceutical Science and Technology Sep 2019, 73 (5) 459-469; DOI: 10.5731/pdajpst.2018.009688
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Keywords

  • single-use system integrity (SUSI)
  • maximum allowable leakage limit (MALL)
  • Single-use system (SUS)
  • microbial ingress testing

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