FDA Announces Availability of a Draft Guidance: “Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology Considerations”

On February 25, 2019, the U.S. Food and Drug Administration (FDA) announced the availability of a draft guidance for industry entitled “Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology Considerations”. This guidance provides recommendations to sponsors planning to conduct food-effect (FE) studies for orally administered drug products as part of investigational new drug applications (INDs), new drug applications (NDAs), and supplements to these applications. The guidance contains recommendations for the conduct, timing, and design of FE studies as well as considerations for data analysis and labeling.

Food-drug interactions can have a significant impact on the safety and efficacy of the drug. These effects can be manifested in different ways. During new drug development, pharmacokinetic studies to assess the effect of food on the systemic exposure of the drug are conducted to determine: (1) if, and to what extent, food impacts the systemic exposure of the drug; (2) whether food increases or decreases the variability of the systemic exposure of the drug; and (3) if the effect of food is different across meals with different fat or caloric contents.

It is important to have a detailed understanding of the exposure-response relationships of the drug to interpret the results of FE studies. For example, the observed increase or decrease in the systemic exposures of some drugs in the presence of food may not be clinically relevant based on exposure-response information. In other cases, the clinical pharmacology characteristics of the drug may suggest that it should be administered only under fasted conditions (e.g., when higher exposures under fed conditions raise the risk of a clinically significant adverse reaction). Some drugs have undesired side 68effects that can be alleviated when taken with a meal. Food may increase absorption, and co-administration with food may be the only practical means of enhancing the efficacy of the drug in patients.

This guidance revises and replaces part of the 2002 FDA guidance for industry entitled “Food-Effect Bioavailability and Fed Bioequivalence Studies”. Information on fed BE studies to be submitted in abbreviated new drug applications (ANDAs) is now found in the FDA guidance for industry entitled “Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA”. Specific recommendations concerning fed comparability trials are now described in the FDA guidance for industry entitled “Bioavailability Studies Submitted in NDAs or INDs — General Considerations”. Sponsors are strongly encouraged to engage FDA staff early in the development of a new drug regarding the strategy and details of FE studies.

The “Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology Considerations” guidance is available at https://go.usa.gov/xEyuj. Please refer to the guidance for more details.

FDA is publishing this draft guidance to collect additional public comments. You may submit your comments to the draft guidance by April 29, 2019 to the docket (Docket No.FDA-2018-D-4368) available at https://www.regulations.gov. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience, and make your voice count.

The Office of Clinical Pharmacology (OCP) is pleased to offer the e-mail subscription service Clinical Pharmacology Corner. This is a free service from FDA to provide occasional updates from OCP regarding newly approved therapies, new regulatory and scholarly publications, upcoming events and other items of interest. Subscribe today at http://go.fda.gov/subscriptionmanagement (note: this link does not work with Internet Explorer) and select Clinical Pharmacology Corner under Drugs.

We always welcome your thoughts regarding the format, content, and utility of this communication. Comments may be sent via email to [email protected].

This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.