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Early Consideration on Food Effect Evaluation for Oral Drug Products in Japan

2026.04.27

• Early Consideration Papers
• PMDA

Introduction to Early Consideration on Food Effect Evaluation

According to the notification issued by Pharmaceuticals and Medical Devices Agency (PMDA) on March 30, 2026, a new Early Consideration document outlines key scientific perspectives on evaluating the impact of food on the pharmacokinetics of oral drug products.　This document reflects evolving global practices and scientific knowledge, providing flexible, practical guidance to support innovative drug development. As an Early Consideration, it represents the current thinking based on available evidence and may be updated as new data emerge.

Importance of Food Effect Evaluation in Oral Drug Development

Food intake can significantly influence gastrointestinal absorption and drug exposure. Therefore, understanding food effects is critical for defining appropriate dosing regimens and ensuring drug efficacy and safety in clinical use. Traditionally in Japan, food effect (FE) studies have been expected to be conducted using the “final formulation.” However, global practices (e.g., FDA and EMA) allow for more flexibility depending on formulation characteristics and development stage.

Consideration for Bioequivalence between Formulations: Use of a Pilot-scale lot manufactured Formulation for the FE studies

The guidance introduces a key concept: if bioequivalence is demonstrated between an early pilot-scale lot and a final registration/commercial-scale lot, it is reasonable to expect minimal differences in food effects for these formulations. And no additional FE study would be required for the final formulation.

Therefore, if:

• A food effect study is conducted using a pilot-scale lot formulation, and
• Bioequivalence between the pilot-scale lot and a final registration/commercial-scale lot can be adequately justified in the FE assessment.

then repeating the FE study with the final formulation may not be necessary.

Considerations Based on BCS Classification (High Solubility & High Permeability)

For immediate-release products containing highly soluble and highly permeable drug substances (e.g., BCS Class I):

• No significant food effect on AUC has generally been observed in past Japanese approval data
• If no food effect on AUC is confirmed using a development formulation, it may be extrapolated to the final formulation

However:

• Cmax may still be affected by food even in such cases
• If Cmax is clinically relevant for efficacy or safety, careful evaluation using the final formulation is still required

Conditions Where FE Study with the Registration Batch Formulation May Be Waived

The document suggests that additional FE studies using the final formulation may not be required if all of the following conditions are met:

• Immediate-release formulation with high solubility and high permeability
• Cmax is not critical for efficacy and safety
• No food effect on AUC observed in development-stage formulation

Sponsors are encouraged to consult with PMDA through formal advice procedures to confirm acceptability.

Alignment with Global Regulatory Practices

The guidance reflects increasing alignment with international regulatory approaches:

• The U.S. Food and Drug Administration (FDA) allows waivers of FE studies under certain BCS-based conditions
• The European Medicines Agency (EMA) acknowledges flexibility depending on formulation changes during development

Japan’s clarification of these concepts reduces ambiguity and supports more efficient global development strategies.

Conclusion

This Early Consideration provides a more flexible and science-based framework for evaluating food effects in oral drug development in Japan. By allowing the use of investigational formulations (pilot-scale lots) under justified conditions and aligning with global practices, PMDA is enabling more efficient clinical development while maintaining scientific rigor.

Reference

000279989.pdf