title: High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 3. Chemical Stability and Visual Appearance of a Protein-Based Aqueous Solution for Injection as a Function of HVLD Exposure.
abstract: This Part 3 of this three-part research series reports the impact of high-voltage leak detection (HVLD) exposure on the physico-chemical stability of the packaged product. The product, intended for human administration by injection, is an aqueous solution formulation of the rapid acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. The package is a small-volume form-fill-seal plastic laminate bag. Product-packages exposed to HVLD were compared to unexposed product after storage for 9 months at recommended storage conditions of 5 ± 3 °C. No differences in active ingredient or degradation products assays were noted. No changes in any other stability indicating parameter results were observed. This report concludes this three-part series. Part 1 documented HVLD method development and validation work. Part 2 explored the impact of various package material, package temperature, and package storage conditions on HVLD test results. Detection of leaks in the bag seal area was investigated. In conclusion, HVLD is reported to be a validatable leak test method suitable for rapid, nondestructive container-closure integrity evaluation of the subject product-package.
  In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was proven to find hole leaks in small plastic bags filled with a solution of insulin aspart intended for human injection (NovoRapid®/NovoLog® by Novo Nordisk A/S, Bagsværd, Denmark). In Part 2, the ability of the HVLD method to find other types of package leaks was tested, and the impact of package material and product storage temperature on HVLD results was explored. This final Part 3 checked how well the packaged protein drug solution maintained its potency after HVLD exposure over 9 months of storage under long-term stability conditions. Results showed that HVLD caused no harm to the product.
authors.affiliation: Novo Nordisk A/S, Bagsværd, Denmark;
authors.forename: Mats
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Damgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Buus
authors.forename: Dana Morton
authors.initials: DM
authors.lastname: Guazzo
mesh_terms: D004349:Drug Packaging; D004355:Drug Stability; D006801:Humans; D007267:Injections; D061267:Insulin Aspart; D010288:Parenteral Nutrition; D019999:Pharmaceutical Solutions; D019064:Product Packaging; D012996:Solutions
chemical_list: D019999:Pharmaceutical Solutions; D012996:Solutions; D061267:Insulin Aspart
keywords: Container-closure; Container-closure integrity; Defects; Electrical conductivity and capacitance leak detection; Form-fill-seal packages; HVLD; High-voltage leak detection; Leak; Leak detection; Leak test method; Leakage; Package; Package defects; Package integrity; Package integrity method; Plastic laminate bag; Protein product; Stability.