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Research ArticleTechnology/Application

High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 1. Method Development and Validation

Rasmus Damgaard, Mats Rasmussen, Peter Buus, Brian Mulhall and Dana Morton Guazzo
PDA Journal of Pharmaceutical Science and Technology November 2013, 67 (6) 634-651; DOI: https://doi.org/10.5731/pdajpst.2013.00945
Rasmus Damgaard
1Novo Nordisk A/S, Bagsværd, Denmark;
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Mats Rasmussen
1Novo Nordisk A/S, Bagsværd, Denmark;
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Peter Buus
1Novo Nordisk A/S, Bagsværd, Denmark;
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Brian Mulhall
2Whitehouse Laboratories, LLC, Whitehouse, NJ, USA; and
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Dana Morton Guazzo
3RxPax, LLC, Bridgewater, NJ, USA
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  • For correspondence: dguazzo@rxpax.com
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Abstract

In Part 1 of this three-part research series, a leak test performed using high-voltage leak detection (HVLD) technology, also referred to as an electrical conductivity and capacitance leak test, was developed and validated for container–closure integrity verification of a small-volume laminate plastic bag containing an aqueous solution for injection. The sterile parenteral product is the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®, by Novo Nordisk A/S, Bagsværd, Denmark). The aseptically filled and sealed package is designed to preserve product sterility through expiry. Method development and validation work incorporated positive control packages with a single hole laser-drilled through the laminate film of each bag. A unique HVLD method characterized by specific high-voltage and potentiometer set points was established for testing bags positioned in each of three possible orientations as they are conveyed through the instrument's test zone in each of two possible directions—resulting in a total of six different test method options. Validation study results successfully demonstrated the ability of all six methods to accurately and reliably detect those packages with laser-drilled holes from 2.5–11.2 μm in nominal diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product physico-chemical stability.

LAY ABSTRACT: In this Part 1 of a three-part research series, a leak test method based on electrical conductivity and capacitance, called high voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with an insulin pharmaceutical solution for human injection by Novo Nordisk A/S (Bagsværd, Denmark). To perform the test, the package is electrically grounded while being conveyed past an electrode linked to a high-voltage, low-amperage transformer. The instrument measures the current that passes from the transformer to the electrode, through the packaged product and along the package walls, to the ground. Plastic packages without defect are relatively nonconductive and yield a low voltage reading; a leaking package with electrically conductive solution located in or near the leak triggers a spike in voltage reading. Test methods were optimized and validated, enabling the detection of leaking packages with holes as small as 2.5 μm in diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product stability.

  • Container-closure
  • Container-closure integrity
  • Defects
  • Electrical conductivity and capacitance leak detection
  • Form-fill-seal packages
  • High-voltage leak detection
  • HVLD
  • Leak
  • Leakage
  • Leak detection
  • Leak test method
  • Package
  • Package defects
  • Package integrity
  • Package integrity method
  • Plastic laminate bag
  • Protein product
  • Stability
  • Insulin.
  • © PDA, Inc. 2013
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PDA Journal of Pharmaceutical Science and Technology: 67 (6)
PDA Journal of Pharmaceutical Science and Technology
Vol. 67, Issue 6
November/December 2013
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High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 1. Method Development and Validation
Rasmus Damgaard, Mats Rasmussen, Peter Buus, Brian Mulhall, Dana Morton Guazzo
PDA Journal of Pharmaceutical Science and Technology Nov 2013, 67 (6) 634-651; DOI: 10.5731/pdajpst.2013.00945

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High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 1. Method Development and Validation
Rasmus Damgaard, Mats Rasmussen, Peter Buus, Brian Mulhall, Dana Morton Guazzo
PDA Journal of Pharmaceutical Science and Technology Nov 2013, 67 (6) 634-651; DOI: 10.5731/pdajpst.2013.00945
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Keywords

  • Container-closure
  • Container-closure integrity
  • Defects
  • Electrical conductivity and capacitance leak detection
  • Form-fill-seal packages
  • High-voltage leak detection
  • HVLD
  • Leak
  • Leakage
  • Leak detection
  • Leak test method
  • Package
  • Package defects
  • Package integrity
  • Package integrity method
  • Plastic laminate bag
  • Protein product
  • Stability
  • Insulin.

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