Description
This document provides recommendations for sponsors of investigational new drugs (INDs) and applicants submitting new drug applications (NDAs) or biologics license applications (BLAs) on the use of exposure-response information in the development of drugs, including therapeutic biologics. It can be considered along with the International Conference on Harmonisation (ICH) E4 guidance on Dose-Response Information to Support Drug Registration and other pertinent guidances (see Appendix A).
Scope & Applicability
Product Classes
4Products for which this guidance provides clinical development assistance.
A bracketing approach can be applied for stability testing; Drugs made by living organisms or cells.
suggest benefits of controlled-release dosage forms based on concentration-response
drugs with one or more chiral centers
Stakeholders
5Entity responsible for submitting applications under section 524B
reference population for pediatric study assumptions
population for which PK/PD studies are conducted in the decision tree
Way questions are framed is critical to collecting unbiased patient input
Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Attributes
9Cmax may be more informative for safety
factor indicating drug sensitivity to ethnic factors
Diet, environmental factors, cultural or socioeconomic factors; Environmental or cultural factors affecting drug response; Factors known to affect the treatment response
genetic differences or different distribution of gene polymorphisms; Factors like genetics affecting drug response; Factors known to affect the treatment response
Renal or hepatic diseases can alter the binding of drugs to plasma proteins
exposure-response relationship with considerable hysteresis
Condition during chronic maternal dosing for milk sampling
AUC or Cmin may correlate with efficacy
Biological property that may be altered by manufacturing changes; safety narrative should address bioavailability of the ingredients
Identified Hazards
Hazards
1Unexpected and unrecognized risks associated with excessive dosing.
Related CFR Sections (2)
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
See Also (8)
- Collection of Race and Ethnicity Data in Clinical Trials: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Study of Sex Differences in the Clinical Evaluation of Medical Products (Status: Draft)
- Formatting, Assembling and Submitting New Drug and Antibiotic Applications* (Status: Final)
- Format and Content of the Clinical and Statistical Sections of an Application (Status: Final)
- Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products: Guidance for Industry (Status: Final)
- Q5D Quality of Biotechnological/Biological Products: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products; Availability (Status: Final)
- Providing Regulatory Submissions to the Center for Biologics Evaluation and Research (CBER) in Electronic Format - Biologics Marketing Applications: Guidance for Industry (Status: Final)
- Submission of Abbreviated Reports and Synopses in Support of Marketing Applications. (Status: Final)