Are you aware that the ICH M9 guidance on BCS based bio-waivers will take effect in July?

The new guidelines provide recommendations to support the biopharmaceutics classification of drug substances and the Biopharmaceutics Classification System (BCS) based bio-waiver approach.

Two products containing the same drug substance can be considered bioequivalent if their bioavailability characteristics lie within the same predefined molar limits. In-vivo bioequivalence studies are generally used to assess the bioavailability, which can then determine similarity in safety and efficacy.

The BCS system bio-waiver approach is intended to reduce the need for in-vivo bioequivalence studies by providing a “surrogate”. In-vivo studies may be exempted if sufficient in-vitro data is satisfactory to prove bioequivalence. This can be measured by aqueous solubility and intestinal permeability characteristics of a drug, of which the BCS has four categories:

  • Class I: high solubility, high permeability
  • Class II: low solubility, high permeability
  • Class III: high solubility, low permeability
  • Class IV: low solubility, low permeability

The guideline explains when a drug substance is considered highly soluble or highly permeable and how this can be assessed and evaluated, as well as which drugs can be considered for BCS-based bio-waivers. The BCS-based bio-waivers only apply to immediate release, solid oral dosage forms and suspensions which deliver drugs systemically.

“To be eligible for a BCS-based biowaiver, the sponsor should justify why the proposed excipient differences will not affect the absorption profile of the drug substance under consideration, i.e., rate and extent of absorption, using a mechanistic and risk-based approach.”

Decision trees and flow charts are also provided on assessing excipient differences and bio-waiver processes.

Take a look at the 18 page guidance here.