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.Keywords Good manufacturing practice . Vitrification . Ovary . Oncofertility Purpose Current Good Manufacturing Practice (cGMP) regulations are enforced by the US Food and Drug Administration in order to ensure the quality of manufactured drug products. These guidelines are listed in the 21 Code of Federal Regulations (CFR) part 211 [1]. cGMPs include a set of guidelines for facility standards, proper documentation, and implementation of procedures. Additionally, equipment within facilities used for drug manufacturing must be monitored and calibrated under cGMP guidelines and personnel must be properly trained and proficient in the facility procedures in order to be compliant. Current good laboratory practices (cGLPs) are additional guidelines that ensure that the data generated by testing the Capsule The main objective of this study was to establish an easy-to-use kit for standardized ovarian tissue vitrification and recovery. We have described the critical steps, procedures, and environments for manufacturing media kits intended for an Investigational New Drug (IND) application for future clinical trials.Electronic supplementary material The online version of this article

The National Physicians Cooperative: Transforming Fertility Management in the Cancer Setting and Beyond

“…Domestically, products that are manufactured with the intent of receiving FDA approval for clinical use must be produced under an FDA-approved investigational new drug application. Thus, the OC began generating a reliable methodology and material list for an ovarian tissue vitrification kit and a supplementary warming and thawing kit [29]. Kits were based on careful development of protocols with the expertise of cryobiologists, and manufactured using good manufacturing practice requirements and good laboratory practice techniques and validated using nonhuman primate ovarian tissue [30].…”