title: Good manufacturing practice requirements for the production of tissue vitrification and warming and recovery kits for clinical research.
abstract: Products that are manufactured for use in a clinical trial, with the intent of gaining US Food and Drug Administration (FDA) approval for clinical use, must be produced under an FDA approved investigational new drug (IND) application. We describe work done toward generating reliable methodology and materials for preserving ovarian cortical tissue through a vitrification kit and reviving this tissue through a warming and recovery kit. We have described the critical steps, procedures, and environments for manufacturing products with the intent of submitting an IND. The main objective was to establish an easy-to-use kit that would ensure standardized procedures for quality tissue preservation and recovery across the 117 Oncofertility Consortium sites around the globe. These kits were developed by breaking down the components and steps of a research protocol and recombining them in a way that considers component stability and use in a clinical setting. The kits were manufactured utilizing current good manufacturing practice (cGMP) requirements and environment, along with current good laboratory practices (cGLP) techniques. Components of the kit were tested for sterility and endotoxicity, and morphological endpoint release criteria were established. We worked with the intended down-stream users of these kits for development of the kit instructions. Our intention is to test these initial kits, developed and manufactured here, for submission of an IND and to begin clinical testing for preserving the ovarian tissue that may be used for future restoration of fertility and/or hormone function in women who have gonadal dysgenesis from gonadotoxic treatment regimens or disease.
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Laronda
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: McKinnon
authors.affiliation: Division of Reproductive and Developmental Science, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: Alison Y
authors.initials: AY
authors.lastname: Ting
authors.affiliation: Mathews Center for Cellular Therapy, Northwestern Memorial Hospital, Chicago, IL, USA.
authors.forename: Ann V
authors.initials: AV
authors.lastname: Le Fever
authors.affiliation: Division of Reproductive and Developmental Science, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.|Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Zelinski
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. tkw@northwestern.edu.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
mesh_terms: D035843:Biomedical Research; D005260:Female; D006801:Humans; D006080:Ovarian Follicle / Q000502:physiology; D011933:Reagent Kits, Diagnostic; D014481:United States; D014486:United States Food and Drug Administration; D058989:Vitrification
chemical_list: D011933:Reagent Kits, Diagnostic
keywords: Good manufacturing practice; Oncofertility; Ovary; Vitrification