title: High-voltage leak detection of a parenteral proteinaceous solution product packaged in form-fill-seal plastic laminate bags. Part 2. Method performance as a function of heat seal defects, product-package refrigeration, and package plastic laminate lot.
abstract: Part 1 of this three-part research series detailed the development and validation of a high-voltage leak detection test (HVLD, also known as an electrical conductivity and capacitance test) for verifying the container-closure integrity of a small-volume laminate plastic bag containing an aqueous solution formulation of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. Leak detection capability was verified using positive controls each with a single laser-drilled hole in the bag film face. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect weaknesses and/or gaps in the bag heat seal. Study 2 checked the HVLD detection of bag holes in packages stored 4 days at ambient conditions followed by 17 days at refrigeration. Study 3 examined HVLD test results for packages tested when cold. Study 4 compared HVLD test results as a function of bag plastic film lots. The final Part 3 of this series will report the impact of HVLD exposure on product visual appearance and chemical stability.
  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 used to find leaks in small plastic bags filled with a solution for injection of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect bag heat seal leaks. Study 2 checked HVLD's ability to detect bag holes after a total of 21 days at ambient plus refrigerated temperatures. Study 3 looked to see if HVLD results changed for packages tested when still cold. Study 4 compared HVLD results for multiple bag plastic film lots. The final Part 3 of this series will report any evidence of drug component degradation caused by HVLD exposure.
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: Brian
authors.initials: B
authors.lastname: Mulhall
authors.forename: Dana Morton
authors.initials: DM
authors.lastname: Guazzo
mesh_terms: D004349:Drug Packaging; D006358:Hot Temperature; D007263:Infusions, Parenteral; D061267:Insulin Aspart; D010969:Plastics; D019064:Product Packaging; D012034:Refrigeration
chemical_list: D010969:Plastics; 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; Insulin.; Leak; Leak detection; Leak test method; Leakage; Package; Package defects; Package integrity; Package integrity method; Plastic laminate bag; Protein product; Stability