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

摘要

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, Bagsv?rd, 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.