Standard Operating Procedure for Fasted vs Fed Study Design Selection in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/006/2025
Supersedes	SOP/BA-BE/006/2022
Page No.	Page 1 of 12
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define the criteria and process for selecting fasted, fed, or both conditions in bioequivalence (BE) study designs based on pharmacokinetics, regulatory guidance, and the intended labeling of the drug product.

2. Scope

This SOP is applicable to the clinical, pharmacokinetics, regulatory, and medical writing teams involved in planning BA/BE studies for immediate and modified-release formulations intended for global regulatory submissions.

3. Responsibilities

• Clinical Pharmacologist: Evaluates food effect and pharmacokinetic impact from literature and labeling.
• Regulatory Affairs: Confirms requirement for fasted and/or fed conditions from regional guidance and product-specific recommendations.
• Medical Writer: Incorporates study condition rationale into protocol and synopsis.
• Project Manager: Ensures proper study condition alignment with trial design and site readiness.

4. Accountability

The Head of Clinical Development is accountable for ensuring the selected study condition complies with scientific rationale, subject safety, and applicable regulatory requirements.

5. Procedure

5.1 Assessment of Reference Product Labeling

1. Review the SmPC, US Prescribing Information (PI), and reference product monograph.
2. Identify specific food instructions such as:
   • “Take on an empty stomach”
   • “Take with food”
   • No specific instructions
3. Document findings in Annexure-1: Food Labeling Review Table.

5.2 Review of Regulatory Guidance

1. Refer to applicable guidance:
   • USFDA Product-Specific Guidance
   • EMA Bioequivalence Guidelines
   • CDSCO BE Study Guidelines
2. Determine if both fasted and fed studies are mandated or optional.

5.3 Food Effect Consideration Based on Biopharmaceutics

1. Analyze existing data on the following:
   • Absorption rate with/without food
   • Food-induced delay in T_max or increase in C_max
   • Gastrointestinal tolerability under fed condition
2. Discuss risk of food effect with formulation scientists and medical safety officer.

5.4 Determination of Study Conditions

1. Based on the review:
   • Select fasted only design for drugs intended to be taken on an empty stomach and with no food effect.
   • Select fed only design when product is always taken with food due to tolerability or absorption issues.
   • Select both fasted and fed studies when food alters pharmacokinetics or label permits flexibility.
2. Document rationale in Annexure-2: Study Condition Justification Form.

5.5 High-Fat Meal Composition (For Fed Studies)

1. Use standardized high-fat, high-calorie meal as per FDA and EMA guidelines:
   • 800–1000 kcal total
   • Approximately 50% fat content
2. Ensure meal composition is documented and approved by Ethics Committee.

5.6 Final Review and Protocol Documentation

1. Include chosen condition(s) and rationale in the protocol’s “Study Design” and “Rationale” sections.
2. Obtain sign-off from clinical pharmacology and regulatory affairs teams.
3. File all documentation in the eTMF “Study Design Condition” folder.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• PI: Prescribing Information
• SmPC: Summary of Product Characteristics
• T_max: Time to Maximum Plasma Concentration
• eTMF: Electronic Trial Master File

7. Documents

1. Food Labeling Review Table – Annexure-1
2. Study Condition Justification Form – Annexure-2
3. Standard Fed Meal Composition Table – Annexure-3

8. References

• USFDA Guidance for Industry: Food-Effect BA and Fed BE Studies
• EMA Guideline on the Investigation of Bioequivalence
• CDSCO Guidelines for BE Studies in India
• ICH E6(R2) – Good Clinical Practice

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Food Labeling Review Table

Reference Product	Label Instruction	Food Effect Noted	Reviewer	Date
ABC Tablet 50 mg	Take with food	Yes	Rajesh Kumar	10/04/2025

Annexure-2: Study Condition Justification Form

Study Condition	Both Fasted and Fed
Justification	Product labeling allows intake with or without food; food has a moderate effect on PK.
Regulatory Basis	FDA PSG dated Feb 2024

Annexure-3: Standard Fed Meal Composition Table

Component	Food Item	Calories	Fat (%)
Protein	Fried eggs (2)	180	70
Carbohydrate	Butter toast (2 slices)	250	45
Fat	Hash browns	200	80
Dairy	Whole milk (1 glass)	150	50

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
15/01/2022	1.0	Initial SOP for Fasted/Fed Design	New SOP	QA Head
17/04/2025	2.0	Updated Annexures and Regulatory References	Annual SOP Review	QA Head