title: In vitro stability and compatibility of tenecteplase in central venous access devices.
abstract: Central venous access devices (CVADs) aid in the delivery of nutritional support, infusion therapy, and hemodialysis. Maintaining continuous flow through these devices is challenging, because they are susceptible to complications such as thrombi occlusion. Therefore, CVADs may require treatment with anticoagulant or thrombolytic agents. Using these agents as locking solutions has been widely investigated; however, few publications have described the compatibility of the therapeutic with the CVAD itself. The objective of this investigation was to evaluate the in vitro stability and compatibility of a thrombolytic biologic agent, tenecteplase, with various CVAD materials. Tenecteplase was reconstituted to 1 mg/mL with either sterile water for injection or bacteriostatic water for injection (0.9% benzyl alcohol) then incubated in glass vials, polysulfone/silicone vascular access ports, and polyurethane or silicone catheters for up to 96 hours. Biochemical assays including protein monomer, protein one-chain, and in vitro bioactivity were used to assess tenecteplase's compatibility with the investigated diluents and materials every 24 hours. Antimicrobial testing was also performed for up to 28 days on bacteriostatic water for injection-reconstituted samples only. Our results showed tenecteplase to be compatible with both types of diluents (in glass vials) and catheters for up to 72 hours. Furthermore, tenecteplase was compatible with the polysulfone/silicone vascular access ports for up to 24 hours. Finally, bacteriostatic water for injection-reconstituted tenecteplase effectively met USP criteria for the inhibition of growth of micro-organisms. This study serves as an example of a best practice to evaluate the in vitro stability and compatibility of a biologic agent with CVAD materials.
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Genentech Inc., South San Francisco, California, USA. lentz.yvonne@gene.com
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Lentz
authors.forename: Michael
authors.initials: M
authors.lastname: Joyce
authors.forename: Xanthe
authors.initials: X
authors.lastname: Lam
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002405:Catheterization, Central Venous; D002408:Catheters, Indwelling; D002463:Cell Membrane Permeability; D004355:Drug Stability; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase