Alternative Approaches for BE Study of Locally Acting Drugs
Bioequivalence (BE) studies traditionally rely on pharmacokinetic (PK) parameters, but for locally acting drugs—such as inhalation products, nasal sprays, and topical formulations—systemic drug levels may not reflect therapeutic effect. Thus, alternative BE approaches are essential.
Key Methods
Pharmacodynamic (PD) Studies – Instead of plasma drug concentration, PD studies measure surrogate markers or direct clinical effects, such as:
- Bronchodilation measurements for inhalers (e.g., Forced Expiratory Volume in 1 second, FEV1).
- Skin blanching tests for topical corticosteroids.
In Vitro Testing – Comparative dissolution testing, particle size distribution, and drug deposition studies help evaluate equivalence.
Comparative Clinical Studies – When validated PD markers are unavailable, direct clinical trials comparing efficacy and safety may be necessary.
Regulatory Frameworks
Agencies like the FDA and EMA provide specific guidance on alternative approaches for BE assessment of locally acting drugs, such as:
- Inhalation products – Comparative in vitro studies and PD or clinical studies as needed.
- Topical products – In vitro permeation tests (IVPT) and in vivo pharmacodynamic endpoints.
- Ophthalmic formulations – Comparative physicochemical characterization and in vitro release testing.
EMA Guidelines – The EMA emphasizes extensive in vitro testing as a primary pathway for demonstrating equivalence. For inhalation products, guidance mandates lung deposition studies and clinical efficacy trials when necessary. Topical and ophthalmic drug BE pathways focus on physicochemical characterization and validated surrogate markers.
With evolving regulatory expectations, alternative BE strategies ensure robust equivalence assessment while reducing reliance on unnecessary clinical trials.
Read also:
- Factors Affecting Bioequivalence (BE) Results
- Pilot and Pivotal Bioequivalence (BE) Study Strategy for Generics
Resource Person: Pradip Kokane
