Navigating Bioequivalence Study Guidelines Across Global Regulatory Bodies

by

When conducting bioequivalence (BE) or bioavailability (BA) studies for regulatory approval, guidelines from different regulatory bodies must be adhered to. Here’s a summary of the key considerations and variations across major regulatory agencies


Regulatory Guidelines Comparison

USFDA

  • Focus: Bioequivalence for generic drug approval.
  • Acceptance Range: 80–125% for Cmax and AUC with a 90% CI.

Special Cases:

  • Highly variable drugs: Scaled bioequivalence approach.
  • NTI drugs: Tighter limits (90–111.11%).

Study Design:

  • Single-dose, fasting, or fed state based on product label.
  • Population: Preferably 24–36 healthy volunteers, considering variability.

EMA

  • Focus: Generics, biosimilars, and hybrid applications.

Acceptance Range:

  • Standard: 80–125% (Cmax and AUC).
  • Highly variable drugs: Widened limits for C_max (e.g., 75–133%).
  • NTI drugs: Tighter range (90–111.11% for AUC).

Study Design:

  • Single-dose fasting for IR
  • Multiple-dose studies for modified-release forms.
  • Fed State Studies: Required for food-dependent drugs.

WHO

  • Focus: Global harmonization for generics in developing countries.
  • Acceptance Range: 80–125% for C_max and AUC.

Study Design:

  • Fasting state for immediate-release.
  • Fed state for modified-release or food-dependent drugs.
  • Special Considerations: Simplified requirements for essential medicines.

MHRA (UK)

  • Adopts EMA guidelines with specific procedural adjustments.
  • Additional Considerations: Local site-specific requirements for approval.

ANVISA (Brazil)

  • Focus: Both national and imported generics.
  • Acceptance Range: 80–125% for Cmax and AUC.
  • Fed vs. Fasting: Both required for most products.
  • Population: Ethnically diverse volunteers preferred.
  • Local Data Requirement: Studies often need to be conducted in Brazil.

TGA (Australia)

  • Adopts EMA standards but has independent review processes.
  • Additional Guidance: Adjustments for Australian market-specific conditions.

CDSCO (India)

  • Focus: Approvals for domestic and export generics.
  • Guidelines: Based on USFDA and WHO but with local adaptations.
  • Population: Often local volunteers for export markets.
  • Clinical Trials Registry: Mandatory registration in India.


Special Drug Categories

  • Highly Variable Drugs (HVDs): Scaling methods are accepted in many regions.
  • NTI Drugs: Tighter ranges (90–111%).
  • Modified-Release Products: Require fasting, fed, and steady-state studies.


Documentation Requirements

  • Study protocol and report.
  • Ethics committee approvals.
  • Volunteer consent and demographic data.
  • Pharmacokinetic analysis and statistical evaluations.
  • Analytical method validation for drug quantification.


Practical Tips

  • Always consult the latest regulatory guidance documents.
  • Tailor study design to the target market.
  • Engage with local CROs for region-specific compliance.
  • Use bridging studies if submitting data to multiple agencies.


Summary


Read also:


Resource Person: Moinuddin syed. Ph.D, PMP®

Leave a Comment