Description
The purpose of this guidance is to assist sponsors in the development, analysis, and presentation of microbiology data during antibacterial drug development. Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall microbiology development program needed to support clinical development and approval of antibacterial drugs administered systemically as well as microbiology information collected after approval.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Subject of the guidance document regarding development and analysis
Guidance title regarding microbiological data development; Subject of the guidance document regarding microbiological data
Products requiring demonstration of component contribution per regulations
Stakeholders
3responsible for justifying omission of studies
Assist sponsors in the nonclinical evaluation
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Regulatory Context
Regulatory Activities
9Submission to update drug product labeling
The primary regulatory activity addressed in the guidance
Sponsors should discuss the format of microbiology datasets with FDA
Sponsors should discuss the format of microbiology datasets with FDA
Investigational New Drug submissions
New Drug Application
Biologics License Application
IND for treatment use; Regulatory submission required for clinical trials and expanded access.
Rule does not apply to products marketed under an NDA
Document Types
6Cybersecurity information should be included in device labeling
content and format of DI information; The complete labeling document for a drug.; The complete labeling document for prescription drugs; The complete labeling document (FPI) containing detailed drug interaction sections.; Section of drug labeling
Database for clinical trial subject level data
Reports including investigator name, location, and standardized methods
eCTD specifications for regulatory submissions
Submission of long-term stability data
Attributes
8Estimate of the EC of the investigational drug against target bacteria
Susceptibility data that are accompanied by the appropriate QC data
Biological markers characterizing the severity of a pathogen
Characteristic of bacteria to be presented in labeling
Important baseline and prognostic variable for matching control groups.
Characterization of isolates relative to resistance
Proposed biological activity of the drug
Factor influencing in vitro susceptibility test results
Technical Details
Substances
8Tested if they occur as residues in food and have structural alerts
The class of products covered by this guidance
beta-lactamase-positive Haemophilus influenzae
bacteria that causes TSS
Microorganism found in contaminated inks that can cause serious infections
Indicator organism for facility conditions
Type of drug eligible for QIDP.
Enzymes involved in resistance mechanisms
Testing Methods
10Nonclinical studies used to evaluate antibacterial drugs
used to evaluate drug potency and MIC
Correlation of MIC and disk diffusion methods
Standardized methods used to determine the activity of the antibacterial drug
Studies evaluating microbial killing
Used to model drug concentrations
Methods used for generating susceptibility data
Method comparing diffusion testing to dilution testing
Method for characterization of antibacterial interaction
Methodology used to determine MIC and MBC data
Processes
3Methods used during drug development to determine activity
Methods to determine the sensitivity of bacteria to antibacterial drugs
Studies conducted during early development to assess resistance
Clinical Concepts
6elucidation of drug pharmacology
Example of a clinical indication for an antibacterial drug
Overall clinical response such as cure or failure
Subject's status of microbiological eradication in clinical trials
The development of resistance by bacteria to an antibacterial drug
Assessment of drug ability to reach bacteria inside host cells
Identified Hazards
Hazards
3Phenotypic and/or genotypic characterization of isolates relative to resistance
Infections caused by bacteria that the drug is intended to treat
Characterization of isolates relative to virulence characteristics
Standards & References
External Standards
3Methods for Dilution Antimicrobial Susceptibility Tests
Performance Standards for Antimicrobial Susceptibility Testing
Organization developing standard methods for in vitro susceptibility testing.
Specifications
10Synonymous with breakpoints used to interpret AST results.
MBC results in study reports
Minimal inhibitory concentrations for the pathogen of interest
MICs used to measure in vitro susceptibility of B. anthracis.
minimum inhibitory concentration used for PK/PD relationships
Measurement used in diffusion susceptibility testing
Criteria based on limited information before phase 3 trials
Criteria used to interpret susceptibility results as susceptible, intermediate, or resistant; Database for final in vitro antibacterial susceptibility test interpretive criteria
Parameters used to monitor the performance of susceptibility tests
target PK/pharmacodynamic (PD) parameters
Related CFR Sections (1)
- 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics