The FDA’s guidance Assessing the Effects of Food on Drugs in INDs and NDAs- Clinical Pharmacology Considerations, emphasizes the importance of Food-Effect (FE) studies in assessing how food influences the absorption, safety, and effectiveness of orally administered drugs during drug development. Here’s a breakdown of key takeaways:
Why Food Effects Matter?
- Food can alter drug absorption, impacting efficacy and safety.
- High-fat meals generally have the greatest impact.
- The goal: optimize safety and provide clear administration instructions.
When to Conduct Food Effects Studies?
FE studies should be initiated early during drug development. Initial pilot studies with high-fat meals provide preliminary insights, while definitive studies using the final drug formulation confirm the impact of food.
Study Requirements
- FE studies required for new drug products (immediate/modified-release, fixed-combination).
- Test with high-fat meals and consider low-fat meals if needed.
- Pilot studies early in development help guide dosing strategy.
Study Design Considerations
- Crossover designs (fed vs. fasted) are recommended.
- Subject selection should include diverse groups, except where safety concerns exist.
- Use clinically recommended doses unless contraindicated.
Data Analysis
- PK parameters like AUC, Cmax, and Tmax are crucial for understanding food’s impact.
Labelling Implications
- Labelling should clearly inform whether the drug should be taken with or without food based on these findings.
- Example: “Take on an empty stomach at least 2 hours before or 1 hour after food.”
- Example: “Take with a low-fat meal or on an empty stomach.”
Special Populations
- Separate studies not required for geriatric patients.
- Pediatric FE studies can be conducted in adults, with results extrapolated.
Innovative Approaches
- The FDA may waive FE studies for Biopharmaceutics Classification System (BCS) Class 1 drugs due to minimal food impact.
- Model-informed drug development approaches like PBPK modelling are encouraged to complement FE studies.
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Resource Person: Bhupesh Pratap