Non-clinical: toxicology

The European Medicines Agency's scientific guidelines on toxicology help medicine developers prepare marketing authorisation applications for human medicines.

For a complete list of scientific guidelines currently open for consultation, see Public consultations.

Single and repeat-dose toxicity

• Questions and answers on the withdrawal of the note for guidance on single dose toxicity
• Repeated dose toxicity
• ICH S4 Duration of chronic toxicity testing in animals (rodent and non-rodent toxicity testing)

Genotoxicity

• Qualification of non-genotoxic impurities
• ICH S2 (R1) Genotoxicity testing and data interpretation for pharmaceuticals intended for human use
• ICH M7 Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk
• Assessment of the genotoxic potential of antisense oligodeoxynucleotides
• Assessment of the genotoxic potential of antisense oligodeoxynucleotides

Carcinogenicity

• ICH S1 Regulatory notice on changes to core guideline on rodent carcinogenicity testing of pharmaceuticals
• ICH S1A Need for carcinogenicity studies of pharmaceuticals
• ICH S1B Carcinogenicity: testing for carcinogenicity of pharmaceuticals
• ICH S1C (R2) Dose selection for carcinogenicity studies of pharmaceuticals
• Carcinogenic potential
• CHMP SWP conclusions and recommendations on the use of genetically modified animal models for carcinogenicity assessment
• Non-clinical assessment of the carcinogenic potential of human insulin analogues
• Carcinogenicity evaluation of medicinal products for the treatment of HIV infection

Reproductive/developmental and juvenile toxicity

• ICH S5 (R3) Guideline on detection of reproductive and developmental toxicity for human pharmaceuticals
• Risk assessment of medicinal products on human reproduction and lactation: from data to labelling
• Need for non-clinical testing in juvenile animals on human pharmaceuticals for paediatric indications
• Need for assessment of reproduction toxicity of human insulin analogues
• Non-clinical testing for inadvertent germline transmission of gene transfer vectors

Local tolerance

• Non-clinical local tolerance testing of medicinal products

Immunotoxicity

Other toxicity

• ICH S8 Immunotoxicity studies for human pharmaceuticals

Mechanistic studies

• Non-clinical evaluation of drug-induced liver injury (DILI)
• In vitro investigation of mitochondrial toxicity of anti-HIV nucleoside reverse transcriptase inhibitors

Dependence

• Non-clinical investigation of the dependence potential of medicinal products
• Background to the CPMP Position Paper on possible pre-clinical studies to investigate addiction and dependence/withdrawal related to the use of selective serotonin uptake inhibitors (SSRIs)
• Background to the CPMP Position Paper on selective serotonin uptake inhibitors (SSRIs) and dependency/withdrawal reactions

Impurities

• ICH Q3D Elemental impurities
• ICH M7 Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk
• Limitations to the use of ethylene oxide in the manufacture of medicinal products

Other

• ICH S10 Photosafety evaluation of pharmaceuticals
• Regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches
• Replacement of chlorofluorocarbons (CFC) in metered dose inhalation products
• Use of phthalates as excipients in human medicinal products
• Use of methyl- and propylparaben as excipients in human medicinal products for oral use

Specific types of products

Chemicals

• Carcinogenicity evaluation of medicinal products for the treatment of HIV infection
• Assessment of the genotoxic potential of antisense oligodeoxynucleotides
• Investigation of chiral active substances
• In vitro investigation of mitochondrial toxicity of anti-HIV nucleoside reverse transcriptase inhibitors
• Medicinal gases: pharmaceutical documentation (including recommendation on non-clinical safety requirements for well established medicinal gases)
• Genotoxic and carcinogenic potential of phenolphthalein
• Background to the CPMP Position Paper on possible pre-clinical studies to investigate addiction and dependence/withdrawal related to the use of selective serotonin uptake inhibitors (SSRIs)
• Background to the CPMP Position Paper on selective serotonin uptake inhibitors (SSRIs) and dependency/withdrawal reactions

Biologicals

• Need for assessment of reproduction toxicity of human insulin analogues
• Dossier structure and content for pandemic-influenza-vaccine marketing-authorisation application

Advanced-therapy medicinal products

• Non-clinical studies required before first clinical use of gene therapy medicinal products
• Non-clinical testing for inadvertent germline transmission of gene transfer vectors
• Scientific requirements for the environmental risk assessment of gene-therapy medicinal products