Description
This guidance was developed to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
5NCE products requiring structural characterization; Defined in the scope of ICH Q6A
dose selection principles described in ICH S6
conducted only for formulations that substantially alter pharmacokinetics
Safety pharmacology studies may not be needed for locally applied agents
Safety pharmacology studies prior to the first administration in humans may not be needed for cytotoxic agents
Stakeholders
2Guidance developed to help protect clinical trial participants
Primary source of experience data
Regulatory Context
Regulatory Activities
1sponsors should obtain advice from FDA prior to initiating trials for marketing applications; Clinical trials designed to support a marketing application
Attributes
1Nature of the PD effect dependency
Technical Details
Substances
3Metabolites that exhibit dose-proportional and time-independent PK; redistribution of drug or active metabolites from peripheral tissues
Effects of the test substance on the autonomic nervous system
testing of individual isomers should be considered
Testing Methods
9Non-cell-based format that may be appropriate for certain mechanisms of action.
Measurement method for enzymes mentioned in comments
Additional ECG assessment for drugs with large QTc prolongation effects
used to assess central nervous system effects
test for central nervous system assessment
Used to measure cardiac rhythm
used to assess autonomic nervous system effects
used to assess autonomic nervous system effects
used to assess gastrointestinal system effects
Processes
5Studies that investigate potential undesirable pharmacodynamic effects
Pivotal toxicology studies considering disease biology and pharmacology
used to rationally select or design studies
Primary pharmacodynamic studies do not need to be conducted in compliance with GLP.
secondary pharmacodynamic studies do not need to be conducted in compliance with GLP
Clinical Concepts
8Reported outcomes following the use of a drug or drug class.; provide information to predict potential adverse effects in the target species
common feature of antiarrhythmic agents
Potential safety concern/adverse effect of some antiemetic drugs.
chronic, relapsing, and remitting inflammatory bowel disease; Target disease for drug development; The primary disease state addressed by the guidance.
patient population consideration for renal function
Effects of the test substance on the autonomic nervous system should be assessed.
Effects of the test substance on the gastrointestinal system should be assessed.
The thorough QT study is not intended to assess the risk of TdP directly
Identified Hazards
Hazards
1potential effects on organ system functions
Standards & References
Specifications
1Minimum number of animals needed to achieve BE
ICH References (3)
Safety Pharmacology Studies for Human Pharmaceuticals
Nonclinical Safety Studies for the Conduct of Human Clinical Trials
Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Advanced Manufacturing Technologies Designation Program
- Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format Final Rule Questions and Answers
- Q4B Annex 8: Sterility Test General Chapter
- Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products: Draft Guidance for Industry
- Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products: Guidance for Industry
- Failure to Respond to an ANDA Complete Response Letter Within the Regulatory Timeframe Guidance for Industry: Guidance for Industry
- CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports
- Best Practices in Developing Proprietary Names for Human Prescription Drug Products; Guidance for Industry: Guidance for Industry