Evaluation of medicinal products indicated for treatment of bacterial infections - Scientific guideline

This guideline merges, revises and adds to the guidance previously included in the Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (CPMP/EWP/558/95 Rev 2) and the Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (EMA/CHMP/351889/2013).

Keywords: Non-inferiority studies, superiority studies, susceptibility testing, pharmacokinetic / pharmacodynamic (PK/PD) relationship, bacteraemia, febrile neutropenia, eradication of carriage, drug-resistant organisms; paediatric investigation plan (PIP)

Minimum inhibitory concentration (MIC) breakpoints refer to specific concentrations of an active substance expected to have an effect on a clinical infection produced by a given pathogen.

They indicate the probability of treatment success (susceptibility breakpoint) or failure (resistance breakpoint) when administered at an approved dosage and indication.

They are also known as susceptibility testing interpretative criteria (STIC).

These breakpoints can inform physicians of patients with a particularly complex infection, supporting them to identify an appropriate treatment course. 

From 1 December 2022, MIC information is centralised and made available in the document below: 

This document presents MIC information in a tabular format. It contains separate tabs for each active substance, in alphabetical order.

It uses the following abbreviations:

• "S" for susceptibility breakpoints;
• "R" for resistance breakpoints; 
• "IE" for where there is insufficient evidence that a bacteria or group of bacteria is a good target for therapy with a given active substance;
• "IP" for breakpoints are under preparation.  

EMA is relocating this data from the product information (PI) of authorised products in order to ensure that the breakpoints for both centrally and nationally authorised products are kept up to date.

PI documents will continue to provide guidance on the approved dosage of antibacterials.

This data relocation followed the adoption of revision 3 of the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections.

For more information on this guideline, see Current version.

• Clinical efficacy and safety: anti-infectives for systemic use
• Directive 2001/83/EC
• Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections to address paediatric-specific clinical data requirements
• Addendum to the note for guidance on evaluation of medicinal products indicated for treatment of bacterial infections to address indication-specific clinical data requirements
• Addendum to the note for guidance on evaluation of medicinal products indicated for treatment of bacterial infections to specifically address the clinical development of new agents to treat disease due to Mycobacterium tuberculosis
• Application with 1. Meta-analyses; 2. One pivotal study
• Choice of a non-inferiority margin
• Clinical trials in small populations
• Extrapolation of results from clinical studies conducted outside Europe to the EU-population
• ICH E1 Population exposure: the extent of population exposure to assess clinical safety
• ICH E4 Dose response information to support drug registration
• ICH E6 (R1) Good clinical practice
• ICH E8 General considerations for clinical trials
• ICH E9 Statistical principles for clinical trials
• ICH E10 Choice of control group in clinical trials
• ICH E11 Clinical investigation of medicinal products in the paediatric population
• Investigation of drug interactions
• Pharmaceutical development of medicines for paediatric use