Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 2, pp 291–300

Good manufacturing practice requirements for the production of tissue vitrification and warming and recovery kits for clinical research

  • Monica M. Laronda
  • Kelly E. McKinnon
  • Alison Y. Ting
  • Ann V. Le Fever
  • Mary B. Zelinski
  • Teresa K. Woodruff
Technological Innovations

DOI: 10.1007/s10815-016-0846-6

Cite this article as:
Laronda, M.M., McKinnon, K.E., Ting, A.Y. et al. J Assist Reprod Genet (2017) 34: 291. doi:10.1007/s10815-016-0846-6

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 

Supplementary material

10815_2016_846_MOESM1_ESM.pdf (14.3 mb)
Fig. S1Vitrification Kit and Warming and Recovery Kit Instructions. Product insert kit information and instructions. (PDF 14.3 mb)
10815_2016_846_MOESM2_ESM.pdf (39 kb)
Fig. S2Oncofertility Consortium Vitrification Kit Use. Images of manufacturing media and vitrification of tissue. a Image of manufactured media bottles within GMP facility. b Image of bovine ovarian cortical tissue pieces within VS+PXZ—filled straw (black circles around pieces of tissue). c Image of sealed straws filled with tissue wedged within a liquid nitrogen Dewar in liquid nitrogen vapor (black arrow pointing to a straw containing bovine ovarian cortical pieces). The adjacent straws contain pieces of bovine placentomes (orange tissue). (PDF 39 kb)
10815_2016_846_MOESM3_ESM.pdf (106 kb)
Fig. S3Ovarian Tissue TUNEL Controls. Fresh bovine ovarian tissue that was digested with DNase I as a positive controls is shown with TUNEL-positive (green) cells alone or photo-merged with DAPI (blue) staining. (PDF 106 kb)
Suppl. Video 1

Standard Operating Procedure for Preparing Ovarian Tissue for Vitrification Using the Stadie-Riggs Tissue Slicer. Fresh bovine ovaries were prepared using the Stadie-Riggs tissue slicer to achieve 0.5 mm thick pieces of cortex. (MOV 292 mb)

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Monica M. Laronda
    • 1
  • Kelly E. McKinnon
    • 1
  • Alison Y. Ting
    • 3
  • Ann V. Le Fever
    • 2
  • Mary B. Zelinski
    • 3
    • 4
  • Teresa K. Woodruff
    • 1
  1. 1.Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Mathews Center for Cellular TherapyNorthwestern Memorial HospitalChicagoUSA
  3. 3.Division of Reproductive and Developmental Science, Oregon National Primate Research CenterOregon Health and Science UniversityBeavertonUSA
  4. 4.Department of Obstetrics and GynecologyOregon Health and Science UniversityPortlandUSA

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