With the increasing adoption of single-use systems (SUS) in critical stages of biopharmaceutical manufacturing, any lack of system integrity can significantly affect drug product quality and patient safety, as well as incur additional costs due to product loss and disrupted production cycle. This article from Sartorius Stedim Biotech, describes how determining the correlation between liquid leakage and microbial ingress can be used to define MALLs (Maximum Allowable Leakage Limits) of SUS for different process steps. The article also details the development of methods and specifications for implementing reliable physical tests to control the integrity of SUS both at a supplier’s site and point of use.
Just fill out the form below to download this article now.
1 PDA Technical Report 27: Pharmaceutical Package Integrity. Parenteral Drug Association: Bethesda, MD, 1998.
2 ASTM WK64337: Standard Practice for Integrity Assurance and Testing of Single-Use Systems. ASTM International: West Conshohocken, PA, 2018.
3 ASTM WK64975: Test Method for Microbial Ingress Testing on Single-Use Systems. ASTM International: West Conshohocken, PA, 2018.
4 Design, Control, and Monitoring of Single-Use Systems for Integrity Assurance. Bio-Process Systems Alliance: Arlington, VA, 2017.
5 ICH Q9: Quality Risk Management. Fed. Register 71(106) 2006: 2105–2106.
6 Annex 1: Manufacture of Sterile Medicinal Products. EudraLex: The Rules Governing, Medicinal Products in the European Union, Volume 4. The European Commission: Brussels, Belgium, 2010.
7 21 CFR 211.94: Drug Product Containers and Closures. Fed. Register 81, 2016: 81697.
8 Guidance for Industry: Container and Closure Integrity Testing in lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products. US Food and Drug Administration: Silver Spring, MD, 2008.
9 USP <1207> Sterile Product Packaging-Integrity Evaluation; USP <1207.1> Package Integrity and Test Method Selection; USP <1207.1> Package Integrity Leak Test Technologies; USP <1207.3> Package Seal Quality Test Methods. US Pharmacopeia–National Formulary. US Pharmacopeial Convention: North Bethesda, MD.
10 Morton DK, et al. Quantitative and Mechanistic Measurements of Container/ Closure Integrity: Bubble, Liquid, and Microbial Leakage Tests. J. Paren. Sci. Technol. 43(3) 1989: 104–108.
11 Kirsch LE, Nguyen L, Moeckly CS. Pharmaceutical Container Closure Integrity 1: Mass Spectrometry-Based Helium Leak Rate Detection for Rubber-Stoppered Glass Vials. PDA J. Pharm. Sci. Technol. 51(5) 1997: 187–194.
12 Gibney MJ. Predicting Package Defects: Quantification Of Critical Leak Size. Virginia Tech, 2000.
13 Keller SW. Determination of the Leak Size Critical To Package Sterility Maintenance. Virginia Tech, 1998.
14 ASTM F2095: Standard Leak Test for Pressure Decay Leak Test for Nonporous Flexible Packages with and without Restraining Plates. ASTM International: West Conshohocken, PA, 2013.
15 ASTM F2391-05: Standard Test Method for measuring Package and Seal Integrity using Helium as the Tracer Gas. ASTM International: West Conshohocken, PA, 2011.
16 Hogreve M. Sartorius Stedim Biotech GmbH, Deutsches Patent und Markenamt (German Patent and Trademark Office) DE102014013522B4. 30 March 2017.
Corresponding author Marc Hogreve is senior scientist of Integrity Testing (marc. email@example.com); 49-551- 308-3752, at Sartorius Stedim Biotech GmbH in Göttingen, Germany. Carole Langlois is marketing manager, Traditional Vaccines; Katell Mignot is a subject matter expert, Single Use Technologies; and Jean-Marc Cappia is head of Segment Marketing Vaccines, at Sartorius Stedim Biotech in Aubagne, France.
FlexAct, Flexboy, Flexsafe, Flexsafe STR, and Sartocheck are registered trademarks of Sartorius Stedim Biotech GmbH.