From IND to NDA

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> Discovery and drug candidate selection

> First-in-man and IND

> From IND to NDA

When a satisfactory clinical proof-of-concept has been achieved in a Phase II clinical trial, the pharmaceutical drug candidate must then go through the final confirmatory Phase III clinical trial in large groups of patients, usually in a multi-site setting, to document the clinical safety and efficacy before a marketing authorization application (MAA, NDA) can be filed. The preclinical safety program must be expanded and completed to support this actual use of the drug :

  • Repeat-dose toxicology studies matching or longer than the intended patient treatment length; in most cases 13-weeks (but when drugs are intended for chronic or recurring treatment, 26/39-week studies weeks are conducted) plus a treatment-free period to address the reversibility of any adverse effects; performed in the same species as the initial 28-day studies.
  • To support the inclusion of larger numbers of women with child-bearing potential in a clinical trial, reproductive toxicology studies on female fertility, embryo-fetal development and pre and postnatal development are normally completed before submission of the marketing authorization.
  • In general, the potential of the drug candidate to induce cancer in human patients should be investigated in 2-year carcinogenicity studies (can be reduced to 26 weeks for certain transgenic species), preceded by appropriate dose range-finding studies; carcinogenicity studies may not be required for drugs intended for acute or short-term treatment only, for certain biopharmaceuticals, or for anti-cancer drugs intended for treatment of seriously ill human patients with short life expectancy.
  • Special toxicology studies may be required on a case-by-case basis, according to the intended therapeutic indication and target patient group. Such studies may include juvenile toxicology studies, antigenicity or immunotoxicology studies, mechanistic studies, dependence studies, or studies with metabolites or impurities.

All preclinical safety studies, apart from pilot and dose range-finding studies, and specifically designed  pharmacology type and mechanistic studies, must be conducted in accordance with the rules for Good Laboratory Practice.