What Is A High-Fat FDA meal?
A high-fat FDA meal is a standardized meal administered to patients or volunteers when conducting fed state/condition clinical trials for orally administered drug products. The applications of this meal in clinical studies are described in various FDA draft Guidances for Industry:
1) Bioavailability Studies Submitted in NDAs or INDs
2) Assessing the Effects of Food on Drugs in INDs and NDAs
3) Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA
The purpose of the high-fat meal
This standardized meal contains between 55g and 65g of fat. The purpose of this meal is to elicit an extreme physiological response in the gastrointestinal tract so that a drug product can be tested with food in a strictly controlled manner. The high-fat content of the meal can change the way a drug interacts with the food in the stomach and intestine significantly. There are different reasons for exploring the administration of a high-fat meal:
The primary goal is patient safety to make sure the drug behaves in a predictable and safe way when taken with food. Food may increase, decrease or have no effect on the systemic drug level in a patient. The effect of food on a medicine is drug dependant and has to be compared to administration of the drug in the fasted state (without food). For example, nilotinib capsules should not be taken with food and taken either two hours before or one hour after a meal. This is because therapeutic blood levels can be increased which may increase the risk of cardiac side effects.
The second reason is to use the food to help improve the tolerability of drugs by reducing localized gastric irritation of some drugs. This is often the case with non-steroidal anti-inflammatory drugs such as naproxen and is why the administration directions for the patient state “Take with or just after food, or a meal.”
The third reason is to enhance the absorption of an insoluble drug typically by increasing drug solubility and dissolution in the fed condition gastrointestinal fluids; high dose celecoxib capsules are one such example.
The results of these fed condition clinical trials provide the data for patient information leaflets instructing how the medicine should be taken by the patient and whether food affects bioavailability.
How food impacts on drugs in the stomach
In patients with a healthy stomach, a high-fat meal can have multiple effects on the stomach and its fluids. These physiological changes can affect how a drug product interacts in vivo. Firstly, a higher amount of drug- particularly if it’s water insoluble- can dissolve in the fats of the food. Secondly, food has a big influence on the pH of the gastric fluids which are especially important for pH sensitive drugs. Thirdly, fed gastric state fluids have a much longer residence in the stomach than in the fasted state fluids. The combination of these factors can have a dramatic effect on how the drug dissolves and is subsequently presented to the small intestine as the stomach contents are emptied. This may influence how the drug is absorbed and its subsequent pharmacokinetics.
FEDGAS helps your drug development
Biorelevant.com has developed FEDGAS in vitro test media that contain the fat content of a FDA high-fat meal to simulate the in vivo fed state gastric fluids after the high-fat meal. FEDGAS can be used in the vessels of conventional USP Dissolution Apparatus 2 and the availability at three different pH values means drug dissolution at different residence times (early, intermediate and late) can now easily be studied. Dissolution results from these straightforward studies can give valuable insights into drug behaviours that were previously very difficult to investigate. This enables superior matching of a generic test drug to its reference listed drug as well as aiding the development of new drugs by linking in vitro dissolution results with in vivo pharmacokinetic findings. You can learn more about this new product here.