Drug Regulators Publish Guidance on Labeling for Susceptibility Testing for Systemic Antibacterial Drug Products.

The FDA has published guidance on “Updating Labeling for Susceptibility Test Information in Systemic Antibacterial Drug Products and Antimicrobial Susceptibility Testing Devices.  The purpose of this guidance is to inform industry of how the FDA intends to comply with section 1111 of the Food and Drug Administration Amendments Act (FDAAA), which requires FDA to identify and periodically update susceptibility test interpretive criteria for antibacterial drug products and to make those findings publicly available. Because susceptibility test interpretive criteria, susceptibility test methods, and quality control parameters are interrelated, this guidance addresses procedures for updating all three of these elements of labeling of antibacterial drug products for human use. The guidance is also intended to remind drug application holders of their responsibility to update this information in the labeling of their antibacterial drug products. In addition, this guidance provides directions to manufacturers of antimicrobial susceptibility testing (AST) devices for updating labeling regarding susceptibility testing information.

The Importance of Susceptibility Test Interpretive Criteria

Antibacterial susceptibility testing is used to determine if bacteria that are isolated from a patient with an infection are likely to be killed or inhibited by a particular antibacterial drug product at the concentrations of the drug that are attainable at the site of infection using the dosing regimen(s) indicated in the drug product’s labeling. The results from antibacterial susceptibility testing generally categorize bacteria as “susceptible,” “intermediate,” or “resistant” to each antibacterial drug tested. When available, culture and susceptibility testing results are one of the factors that physicians consider when selecting an antimicrobial drug product for treating a patient.

Antibacterial Drug Product Labeling

FDA regulations require that information on susceptibility testing be included in the labeling for antibacterial drug products (see 21 CFR 201.57(c)(2)(i)(C)). The INDICATIONS AND USAGE section of labeling for antibacterial drugs includes the condition(s) for which the product has been found to be safe and effective if used as described in the product labeling. The INDICATIONS AND USAGE section also includes a list of specific microbial organisms for the particular indicated condition(s). The results from culture and susceptibility testing can be used to guide selection of an appropriate antibacterial drug product. Over time, additional information may become available and/or changes may occur regarding the susceptibility of certain bacteria to antibacterial drugs.

Consequently, it is important that the in vitro susceptibility test methods, the susceptibility test interpretive criteria, and the quality control parameters listed in the labeling for a product be reviewed on a regular basis and updated to reflect the most current information.

The FDA approach

Where appropriate, FDA intends to recognize susceptibility test interpretive criteria, and associated test methods and quality control parameters, by publishing annually in a Federal Register notice certain standards developed by one or more nationally or internationally recognized standard development organizations. Under this approach, FDA retains the authority to accept or reject for recognition (based on our scientific judgment) any susceptibility test interpretive criteria, or associated susceptibility test method or quality control parameters, developed by a standard development organization for a specific bacterium treated by a specific approved antibacterial drug product.

Updating Susceptibility Test Information

Holders of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) that are designated as a reference listed drug (RLD) for systemic antibacterial drug products should review their product labeling at least annually to evaluate whether the Microbiology subsection is up to date.

This guidance describes two approaches for application holders to update labeling as follows:

• Updating information in the Microbiology subsection of product labeling by submitting revised product labeling that is in conformance with a standard that has been recognized by the Agency.
• Submitting data that support a change in the information in the Microbiology subsection of product labeling that differs from the Agency’s recognized standard

Applicants Believes No Change to the Labeling is Needed.

If the information in the applicant’s product labeling differs from the standards recognized by the Agency and the applicant believes that changes to the labeling are not needed, the applicant should provide written justification to the FDA within 90 days following the publication of the Federal Register notice.

In-Vitro Diagnostic AST Devices

Where appropriate, FDA intends to recognize susceptibility test interpretive criteria, and associated test methods and quality control parameters, by publishing annually in a Federal Register notice references to standards developed by one or more nationally or internationally recognized standard development organizations. Once FDA has recognized a standard, NDA holders should update their drug labeling as described in section IV and FDA will make the approved, updated drug labeling publicly available. If the susceptibility test interpretive criteria in the labeling for an AST device do not conform with the updated drug labeling, AST device manufacturers should update their labeling to conform with the new, publicly available drug labeling within 90 days.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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