Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 2, pp 291–300 | Cite as

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

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)

References

  1. 1.
    Food and Drug Administration. Current Good Manufacturing Practice in Manufacturing Processing, packing, or Holding of Drugs. [Internet]. 21; Apr 6, 2016. Available from: http://www.ecfr.gov/cgi-bin/text-idx?SID=1970e7dcc6a6fb934d0fb596aad264f9&mc=true&tpl=/ecfrbrowse/Title21/21cfr211_main_02.tpl
  2. 2.
    FDA US. Guidance for Industry CGMP for Phase 1 Investigational Drugs. Rockville; 2008.Google Scholar
  3. 3.
    Donnez J, Dolmans M-M. Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;32:1167–70. Springer US.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wowk B, Leitl E, Rasch CM, Mesbah-Karimi N, Harris SB, Fahy GM. Vitrification enhancement by synthetic ice blocking agents. Cryobiology. 2000;40:228–36.CrossRefPubMedGoogle Scholar
  5. 5.
    Badrzadeh H, Najmabadi S, Paymani R, Macaso T, Azadbadi Z, Ahmady A. Super cool X-1000 and Super cool Z-1000, two ice blockers, and their effect on vitrification/warming of mouse embryos. Eur J Obstet Gynecol. 2010;151:70–1. Elsevier Ireland Ltd.CrossRefGoogle Scholar
  6. 6.
    Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, et al. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology. 2004;48:157–78.CrossRefPubMedGoogle Scholar
  7. 7.
    Ting AY, Yeoman RR, Lawson MS, Zelinski MB. Synthetic polymers improve vitrification outcomes of macaque ovarian tissue as assessed by histological integrity and the in vitro development of secondary follicles. Cryobiology. 2012;65:1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ting AY, Yeoman RR, Campos JR, Lawson MS, Mullen SF, Fahy GM, et al. Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system. Hum Reprod. 2013;28:1267–79. Oxford University Press.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ting AY, Yeoman RR, Lawson MS, Zelinski MB. In vitro development of secondary follicles from cryopreserved rhesus macaque ovarian tissue after slow-rate freeze or vitrification. Hum Reprod. 2011;26:2461–72. Oxford University Press.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cobo A, Diaz C. Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2011;96:277–85. Elsevier Ltd.CrossRefPubMedGoogle Scholar
  11. 11.
    Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, et al. Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod. 2009;24:1670–83.CrossRefPubMedGoogle Scholar
  12. 12.
    Sheikhi M, Hultenby K, Niklasson B, Lundqvist M, Hovatta O. Clinical grade vitrification of human ovarian tissue: an ultrastructural analysis of follicles and stroma in vitrified tissue. Hum Reprod. 2011;26:594–603.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Food and Drug Administration. General Labeling Provisions. Code of Federal Regulations Title 21; Apr 1, 2015 pp. 1–17.Google Scholar
  14. 14.
    National Institutes of Health. RFA-RM-10-001: Institutional Clinical and Translational Science Award (U54) [Internet]. 2016 [cited 2016 May 11]. pp. 1–40. Available from: http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-10-001.html#SectionI
  15. 15.
    Huang L, Mo Y, Wang W, Li Y, Zhang Q, Yang D. Cryopreservation of human ovarian tissue by solid-surface vitrification. Eur J Obstet Gynecol Reprod Biol. 2008;139:193–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Kagawa N, Silber S, Kuwayama M. Successful vitrification of bovine and human ovarian tissue. Reprod BioMed Online. 2009;18:568–77. Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB UK.CrossRefPubMedGoogle Scholar
  17. 17.
    Bao RM, Yamasaka E, Moniruzzaman M, Hamawaki A, Yoshikawa M, Miyano T. Development of vitrified bovine secondary and primordial follicles in xenografts. Theriogenology. 2010;74:817–27. Elsevier Inc.CrossRefPubMedGoogle Scholar
  18. 18.
    Hashimoto S, Suzuki N, Yamanaka M, Hosoi Y, Ishizuka B, Morimoto Y. Effects of vitrification solutions and equilibration times on the morphology of cynomolgus ovarian tissues. Reprod BioMed Online. 2010;21:501–9. Reproductive Healthcare Ltd.CrossRefPubMedGoogle Scholar
  19. 19.
    Suzuki N, Hashimoto S, Igarashi S, Takae S, Yamanaka M, Yamochi T, et al. Assessment of long-term function of heterotopic transplants of vitrified ovarian tissue in cynomolgus monkeys. Hum Reprod. 2012;27:2420–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30:608–15.CrossRefPubMedGoogle Scholar
  21. 21.
    Amorim CA, Dolmans M-M, David A, Jaeger J, Vanacker J, Camboni A, et al. Vitrification and xenografting of human ovarian tissue. Fertil Steril. 2012;98:1291–2. Elsevier Inc.CrossRefPubMedGoogle Scholar
  22. 22.
    Amorim CA, Jacobs S, Devireddy RV, Van Langendonckt A, Vanacker J, Jaeger J, et al. Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue. Hum Reprod. 2013;28:2146–56.CrossRefPubMedGoogle Scholar
  23. 23.
    Dolmans M-M, Binda MM, Jacobs S, Dehoux JP, Squifflet JL, Ambroise J, et al. Impact of the cryopreservation technique and vascular bed on ovarian tissue transplantation in cynomolgus monkeys. J Assist Reprod Genet. 2015;32:1251–62.CrossRefPubMedPubMedCentralGoogle Scholar

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

Personalised recommendations