09/10/2024

Photo by Michał Parzuchowski on Unsplash

In August 2024, the US Food and Drug Administration (FDA) released a final guidance for industry on drug-drug interactions (DDI) with The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) titled: M12 Drug Interaction Studies. The guidance is intended to set the global standard and framework for conducting and reporting DDI studies in order to improve the efficacy of drugs as well as the safety and predictability of potential interactions between different drugs (for supplementary information the FDA has also released a Q&A document about the guidance). Following this release the FDA announced an upcoming webinar on October 9th, 2024 1:00 PM ET, for researchers, regulators, and other stakeholders in the pharmaceutical industry, especially those involved in pharmacokinetics and pharmacodynamics; to learn more about this guidance and to voice any questions or concerns they may have regarding future implementations.

The webinar will consist of presentations from FDA officials and industry experts including an overview of the new guidance as well as similarities and difference between this guidance and the previous on In Vitro and Clinical DDI studies. Other topics of discussion include:

In Vitro evaluations of DDIs: Whether DDIs are mediated by CYP and UGT enzymes, drug transporters, or other metabolites from an investigational product (IP) is often first determined during In Vitro experiments. These studies will also reveal if the IP acts as an inducer, inhibitor, or substrate to the mediating enzymes, transporters, or metabolites. It is important to not only see how one drug reacts with another in a controlled environment but also within the actual human body.
Data Interpretation and Reporting: Having a globally unified method for interpreting DDI results and reporting the same endpoints will streamline drug development in a safe and effective way by avoiding the redundancy of repeating studies and allows researchers to better predict potential DDIs. The guidance provides a list of endpoints and values that should be reported in DDI studies as well as acceptable methods of displaying the data in the reports.
Risk Assessment and Risk Management: The guidance states that a DDI is clinically relevant if the concomitant use of the drugs leads to safety, effectiveness, or tolerability concerns greater than those present when drugs are administered alone. Ideally drug concentrations of the substrate drug should fall within the no-effect boundaries meaning the change is systemic exposure to the drug is not significant enough to require clinical intervention. DDI management strategies should be implemented that address multiple factors which include but are not limited to (for a full list, see section VI of the guidance):
- The expected duration of concomitant drug use – Will the patient be taking it once, on a short-term or long-term basis?
- The mechanism of the DDI – Is the drug an inhibitor, either reversible of time- dependent inhibition (TDI), or an inducer?
- The ability to interrupt the IP or concomitant interacting medication – If the patient starts to have an adverse reaction to the given dose, can researchers intervene to stop it?

Certificates for real-time attendance at the webinar will be issued during the two weeks following the event and will be used in support of continued education for the following professional organizations:

Regulatory Affairs Professional Society (RAPS)
Society of Clinical Research Associates (SORCA)
Society of Quality Assurance (SQA)
Association of Clinical Research Professionals (ACRP)

More details regarding the certificates and the webinar can be found on the FDA website at the following link: https://www.fda.gov/drugs/news-events-human-drugs/ich-m12-drug-drug-interaction-studies-final-guidance-10092024. To sign up for the event there is no cost, simply click here and fill in the required fields under Register Now from now until the event begins on October 9th, 2024.

-The Clinical Pathways Team

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