Regulations - References

Important guidelines

• Guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The ICH body includes – among others – the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Ministry of Health, Labor and Welfare (MHLW)
  Of particular importance for preclinical safety are
  • Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals M3(R2) This is the general guideline for developing drugs regulating what is when and in which quality available
  • Other preclinical safety guidelines
• Guidelines of the Organization for Economic Co-operation and Development (OECD), especially for outlines of in vitro and in vivo studies
• National guidelines, e.g. of the
  • US Food and Drug Administration (FDA)
  • Japanese Ministry of Health, Labor and Welfare (MHLW): no English website with guidance documents; but see e.g. Regulatory Information Task Force of the Japan Pharmaceutical Manufacturers Association
• National guidelines have taken over the ICH guidelines, but regulate additional topics omitted by ICH, such as extrapolation of the dose determined experimentally in one species to other species, requirements for premarketing evaluation of drug-induced liver injury, testing in special populations (see below), etc.
• The same holds also true for regional guidelines, e.g. of the European Medicines Agency (EMA)
• Guidelines for testing of special populations, e.g. the pediatric guidelines
  Drug candidates and registered drugs with new indications, formulations or routes of application, if not exempt because of a deferral or waiver, have to be tested in pediatric patients generally before registration according to a special pediatric investigation plan (PIP). For guidance see e.g.
  • EMA
  • FDA
• Guidelines for special indications as e.g. guidelines for vaccine candidates. For the latter there are many different and partly very specific guidelines. The most important ones are those of World Health Organization (WHO), especially
  • WHO Technical Report Series, No. 927, 2005 – Annex 1 – WHO guidelines on nonclinical evaluation of vaccines
  • WHO Expert Committee on Biological Standardization – Sixty-fourth report (2013, published also in 2014) – Annex 2 – Guidelines on the nonclinical evaluation of vaccine adjuvants and adjuvanted vaccines

Data have to be submitted to FDA according to SEND standards.