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Why and How Did Reproduction Toxicity Testing Make Its Early Entry into and Rapid Success in ICH?

  • Rolf Bass
  • Yasuo Ohno
  • Beate Ulbrich
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 5)

Abstract

The need for routine testing of future medicinal products for toxicity to reproduction and development became obvious through the thalidomide disaster. New legal requirements were created, leading to introduction of different testing schemes all over the world. When attempting to fulfil requirements worldwide, somewhat nonsensical piling up of test packages occurred with undue duplication wasting animals.

The ICH topic of reproductive toxicity testing benefited from an already well-oiled machinery of networked experts spanning all ICH parties. Scientifically sound and supported by the six-pack, a draft guideline was presented and accepted, calling for a most probable option with three tests focusing on early embryonic development, organogenesis and postnatal development. An apparent dent, how to best accommodate male fertility testing, was also resolved scientifically and agreed by ICH 2.

Keywords

Medicinal Product Male Fertility European Economic Community Reproductive Toxicity Male Reproductive Organ 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Bass R (1991) Proposal for the development of a uniform tripartite guideline. In: D’Arcy and Harron (eds) Proceedings of the first international conference on harmonization, Brussels, pp 279–288 (discussion: 289–293)Google Scholar
  2. Bass R (1994) Report on progress since ICH 1: Safety (2), Development of the reproductive toxicology guidelines to become one of the first to complete the ICH process. In: D’Arcy and Harron (eds) Proceedings of the second international conference on harmonization, Brussels, pp 33–38Google Scholar
  3. Bass R, Ulbrich B (1991) Draft guideline on detection of toxicity to reproduction for medicinal products – Draft No. 12. Adverse Drug React Toxicol Rev 9(3):127–141Google Scholar
  4. Bass R et al (1991) Draft guideline on detection of toxicity to reproduction for medicinal products – Draft No. 17. Adverse Drug React Toxicol Rev 10(3):143–154Google Scholar
  5. Christian MS (1992) Harmonization of reproductive guidelines: perspective from the International Federation of Teratology Societies. J Am Coll Toxicol 11(3):299–302CrossRefGoogle Scholar
  6. Christian MS (2001) Test methods for assessing female reproductive and developmental toxicology. In: Wallace Hayes A (ed) Principles and methods of toxicology, 4th edn. Taylor & Francis, Philadelphia, PA, pp 1301–1381Google Scholar
  7. Council Directive 65/65/EEC (of 26 January 1965) On the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products. OJ L 22:369Google Scholar
  8. Council Directive 75/318/EEC (of 20 May 1975) On the approximation of the laws of the Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of proprietary medicinal products. OJ L 147:1–12Google Scholar
  9. Diener RM (1991) Timing and utility of behavioural studies in developmental toxicology. In: D’Arcy PF, Harrison (eds) Proceedings of the first international conference on harmonization, Brussels, pp 273–279Google Scholar
  10. European Union (EU)-Legislation: EUDRALEX: Volume 3: Scientific guidelines for medicinal products for human use: see now EMA Web siteGoogle Scholar
  11. ICH S5(R2) (2000) Safety guidelines: detection of toxicity to reproduction for medicinal products and toxicity to male fertility. In: ICH Web site (IFPMA)Google Scholar
  12. ICH S5a (1993) Harmonised tripartite guideline on detection of toxicity to reproduction for medicinal productsGoogle Scholar
  13. ICH S5a(R1) (1995) Toxicity to male fertility, an addendum to the ICH tripartite guideline on detection of toxicity to reproduction for medicinal productsGoogle Scholar
  14. Jödicke B, Neubert D (2004) Reproduktion und Entwicklung. In: Marquardt, Schäfer (eds) Lehrbuch der Toxikologie, chap 21, 2nd edn. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 419–544Google Scholar
  15. Lumley CE (1991) Proposal for international guidelines for reproductive ad developmental toxicity testing for pharmaceuticals. Adverse Drug React Toxicol Rev 10(3):143–153Google Scholar
  16. M3 (1997) Non-clinical safety studies for the conduct of human clinical trials for pharmaceuticalsGoogle Scholar
  17. M3(R2) (2009) Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. In: ICH Web site (IFPMA)Google Scholar
  18. MHLW (1989) Notification: Report of review of the guideline for the detection of influence of pharmaceuticals on reproduction. Yakushin No 118 (1989.9.11)Google Scholar
  19. OECD (1981) Guidelines for testing of chemicals. Sect 4: Health effects. Guideline No. 414: Teratogenicity. OECD, ParisGoogle Scholar
  20. OECD (1983a) Guidelines for testing of chemicals. Sect 4: Health effects. Guideline No. 415: One generation reproduction toxicity study. OECD, ParisGoogle Scholar
  21. OECD (1983b) Guidelines for testing of chemicals. Sect 4: Health effects. Guideline No. 416: Two generation reproduction toxicity study. OECD, ParisGoogle Scholar
  22. Omori Y (1991) Principles and guidelines—a review of recommendations (on detection of toxicity) in the three regions. In: D’Arcy PF, Harrison (eds) Proceedings of the first international conference on harmonization, Brussels, pp 256–266Google Scholar
  23. Peters PWJ, Garbis-Berkvens JM (1996) Methods in reproductive toxicology. In: Niesink RJM et al (eds) Toxicology: principles and applications. CRC, Boca Raton, FL, pp 949–974Google Scholar
  24. Sakai T et al (2000) Collaborative work to evaluate toxicity on male reproductive organs by 2-week repeated dose toxicity studies in rats. J Toxicol Sci 25(Spl Issue):1–21PubMedCrossRefGoogle Scholar
  25. Sanbuissho A et al (2009) Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Toxicol Sci 34(Spl Issue):SP1–SP22PubMedCrossRefGoogle Scholar
  26. Sjöberg P, David RJ (2013) Non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals—ICH M3 and M3(R2). In: van der Laan JW, DeGeorge JJ (eds) Global approach in safety testing. AAPS advances in the pharmaceutical sciences series 5. Springer, New YorkGoogle Scholar
  27. Sullivan FM, Watkins WJ, van der Venne MTh (eds) (1993) The toxicology of chemicals. Series two: Reproductive toxicology, vol 1: Summary reviews of the scientific evidence. EUR 12029 EN 14991Google Scholar
  28. Takayama S (1991) Proposal or mutual acceptance of studies. In: D’Arcy PF, Harrison (eds) Proceedings of the first international conference on harmonization, Brussels, pp 266–269Google Scholar
  29. Takayama S et al (1995) Studies on the optimal treatment period and parameters for detection of male fertility disorder in rats-introductory summary. J Toxicol Sci 20:73–82CrossRefGoogle Scholar
  30. Van Cauteren H (1991) Panel presentation. In: D’Arcy PF, Harrison (eds) Proceedings of the first international conference on harmonization, Brussels, p 289Google Scholar
  31. van der Laan JW et al (2012) Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches—a workshop report. Regul Toxicol Pharmacol 63:115–123PubMedCrossRefGoogle Scholar
  32. Weissinger J (1991) Commentary on proposal for mutual acceptance and proposed alternative approaches. In: D’Arcy PF, Harrison (eds) Proceedings of the first international conference on harmonization, Brussels, pp 269–273Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Pharmaceutical MedicineUniversity of BaselBaselSwitzerland
  2. 2.Pharmacology and ToxicologyCharitéBerlinGermany
  3. 3.BfArMBonnGermany
  4. 4.Berlin–TempelhofGermany
  5. 5.National Institute of Health SciencesTokyoJapan
  6. 6.BFRBerlinGermany

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