February 25, 2019
“How a drug is absorbed by the body is one of the critical features that the FDA evaluates as part of its review of new drugs. There are many factors at play to properly formulate a drug so that it’s released into the body in the most effective and efficient way to achieve clinical effect. In addition to the makeup of the drug itself, the way it’s absorbed in the body may change based on our own physiology, whether or not we take a drug with food, and even what types of food we eat throughout the day. All of this can impact the drug’s efficacy and safety,” said FDA Commissioner Scott Gottlieb, M.D. “For example, certain drugs may be absorbed by the body faster when taken with a high-fat meal; and faster absorption may cause an excessive response or other health issues. In other cases, food may not have a clinically meaningful impact on the drug whatsoever. Today we’re releasing new recommendations for companies on how to conduct food effect studies early in drug development, to promptly uncover potential issues. These recommendations can help identify absorption challenges earlier in the development process and result in safer and more effective medicines and better information for patients. It can also help make drug development more efficient. If, for example, a company determines there’s no food effect on absorption, they may be able to conduct pivotal trials without regard to food. Another type of study important to early drug development, bioavailability or BA studies, examines the rate and amount of an active ingredient absorbed by the body as one measure of the product’s overall effect. These studies provide crucial information on the precise formulation and dose to optimize efficacy and safety and are typically done in healthy adults before the drug is tested on patients. Today we’re also announcing our latest thinking on how to conduct these bioavailability studies, including study design considerations, to better evaluate different dosage forms and even special topics like studying the effect of alcoholic beverages on modified-release drugs. The overall goal of these guidances is to help uncover problems earlier in the development process and lead to better drugs and more information for patients on the effect of their medicines.”
Today, the U.S. Food and Drug administration is making available a draft guidance, Assessing the Effects of Food on Drugs in INDs and NDAs – Clinical Pharmacology Considerations, that when finalized, will provide guidance to companies submitting investigational new drug applications, new drug applications or supplemental applications on how food-drug interactions can meaningfully impact pharmacokinetics and pharmacodynamics of some drugs. For patients, these interactions can potentially lead to increased or reduced drug absorption and efficacy. The severity and frequency of adverse events can also be impacted by food. Well-conducted food effect trials can inform how, when and why drugs should or should not be administered with food. Generally, the FDA is recommending in this draft guidance that companies conduct food effect studies before pivotal trials for all new chemical entities and in certain other scenarios, including for modified-release or combination products of new or approved drugs.
The FDA is also making available a draft guidance, Bioavailability Studies Submitted in NDAs or INDs — General Considerations, that when finalized, will provide guidance to sponsors planning to include bioavailability (BA) information for drug products in investigational new drug applications (INDs), new drug applications (NDAs) and NDA supplements. Bioavailability relates to the rate and extent of active ingredient absorbed by the body and available at the site of action. Bioavailability data for orally administered drug products can inform on the overall performance of the product and its safety and efficacy. The guidance provides information on conducting relative bioavailability studies during the IND period for a drug that a sponsor plans to submit for approval in an NDA as well as bioequivalence (BE) studies during the post approval period for certain changes to drug products. This guidance will revise and replace the FDA’s March 2014 draft guidance for industry entitled Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations, which addresses BA or BE studies for INDs, NDAs and NDA supplements.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.