title: Long term stability of lyophilized plasmid DNA pDERMATT.
abstract: In this short note we report on the shelf-life stability of pDERMATT (plasmid DNA encoding recombinant MART-1 and tetanus toxin fragment-c) 2mg lyophilized powder for reconstitution for intradermal administration, used in an in-house, investigator-initiated clinical phase I study. pDERMATT was stored at 25°C/60% relative humidity (6 months), 2-8°C (24 months), and -20°C (66 months) in the dark and analyzed at several timepoints during the conduct of the clinical study for appearance, identity, purity (plasmid topology), content and residual water content. pDERMATT appeared stable at all storage conditions for the periods tested which, although patient inclusion in the study was significantly delayed, ensured the clinical supply needs. This study shows that lyophilization is an useful tool to preserve the quality of the pDNA and can prevent the need for costly and time-consuming additional manufacture of drug product in case of study delays, not uncommon at the early stage of drug development. To our knowledge, this is the first study reporting shelf life stability of a pDNA formulation for more than 5 years.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands. Iris.vanderHeijden@slz.nl
authors.forename: Iris
authors.initials: I
authors.lastname: van der Heijden
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
mesh_terms: D019496:Cancer Vaccines; D004247:DNA / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D006813:Humidity; D058965:MART-1 Antigen / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D010957:Plasmids; D013696:Temperature; D013744:Tetanus Toxin / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines; D058965:MART-1 Antigen; D010446:Peptide Fragments; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; D004247:DNA
keywords: Lyophilization; Plasmid DNA; Stability; Topology