Think bioequivalence (BE) always means lengthy clinical trials and plasma sampling? Think again. Regulatory science is evolving and with it, a suite of alternative approaches and waivers that can replace or reduce in vivo BE testing. Whether you're working with oral solutions, high-solubility drugs, or multiple strengths of a formulation, there's a scientifically justified shortcut waiting to be explored.
1. Self-Evident Bioequivalence
For simple dosage forms, bioequivalence (BE) may be considered self-evident, and an in vivo study may not be required. The product falls into one of the following categories:
Parenteral, Ophthalmic, or Otic Solutions: The product is a parenteral (injectable), ophthalmic, or otic solution containing the same active and inactive ingredients in the same concentration as an already approved drug.
Inhalation Gases: The product is administered by inhalation as a gas, such as a medicinal or inhalation anesthetic, and contains the same active ingredient in the same dosage form as an approved drug.
Certain Solutions: The product is a solution intended for application to the skin, an oral solution, elixir, syrup, tincture, solution for aerosolization or nebulization, nasal solution, or a similar solubilized form. It must contain the same active ingredient in the same concentration and dosage form as an approved drug and have no inactive ingredients or formulation changes that could significantly affect absorption or availability.
2. BCS-Based Biowaivers (ICH M9)
In vitro dissolution replaces in vivo studies for certain high-solubility drugs.
Exclusions: NTI drugs, modified-release products, buccal/sublingual forms, ODTs without water.
3. Biowaivers for Additional Strengths (ICH M13B)
Skip extra BE studies if one strength (biobatch) meets key criteria.
Bracketing approach: Test lowest & highest strengths if criteria aren’t met.
4. Modified-Release Products
Waivers possible if formulation and release mechanisms are consistent.
5. DESI-Effective Drugs
Waiver granted if dissolution data is published in the Federal Register.
6. Alternative Reference Standards
Not a waiver, but a workaround when the RLD is unavailable.
7. Other BE Approaches
When PK studies aren’t feasible, alternative scientific methods apply.
These pathways aren’t shortcuts they’re scientifically validated strategies that uphold regulatory rigor while streamlining development. For formulators, regulators, and innovators alike, the future of BE is flexible, data-driven, and surprisingly efficient.
Read also: Challenging Scenario in Dissolution Justification for Biowaiver
