Focus on biowaiver approach


Published 8 October 2019

Read the article and learn more about biowaiver approach with our prominent course director Jean-Michel Cardot.


Jean-Michel Cardot

Jean-Michel Cardot
Professor at Clermont-Auvergne University, France

Regulatory agencies have long recognized that, for some drug products, in vivo BA/BE may be self-evident, and, as such, will waive the requirement for in vivo evidence and grant a biowaiver. The use of a biowaiver approach is in the spirit of avoiding unnecessary human testing whenever possible. Five types of biowaivers existed :

  • Biowaiver based on the fact that the dug is in solution when administered
  • Biowaivers based on Biopharmaceutical Classification System (BCS) for solid Immediate Release (IR) oral formulation
  • Biowaivers for different strength for oral formulations
  • Biowaivers based on IVIVC
  • Biowaivers for drug administered locally for a local action (no effective systemic concentrations)


Biowaiver for liquid formulation are based on comparison of formulation as well as specific in vitro requirements.

Biowaivers for both Class I (highly soluble, high intestinal permeability, rapidly dissolving) and Class III (highly soluble, low in intestinal permeability, very rapidly dissolving) IR drug products are possible if they exhibit similar in vitro dissolution profile under all gastric and intestinal luminal pH conditions i.e. pH 1.2 to 6.8, and have a similar composition.

Biowaivers for additional strengths could be applied for IR and MR drug oral products when successful in vivo data are available on higher strength or under bracketing approach, when composition characteristics are fulfilled, and dissolution successful. Some specificities existed on the strength to be investigated in vivo, formulation suitability for dissolution biowaiver, and dissolution studies for additional strength biowaivers.

Biowaivers based on IVIVC suppose a preexistent validated relationship model between in vitro and in vivo data. Based on this relationship any new batch in vivo outcome could be simulated based on in vitro data, and its possible equivalence to the reference product assessed.

Biowaivers for locally acting locally applied drug are based on absence of relevant in vivo blood concentrations related to efficacy and a local action of the drug. Depending of the mechanism of action, formulation equivalence between formulations could be supported only by in vitro tests.

Equally applicable within the private sector, the key focus here is a “ we only pay for what we get” thus providing a robust gated risk management approach; closely aligned with the key principles of liquidated damages.

Those approaches could be used for generic, new drugs, fixed dose combination, well establish used development as well as in the scope of variation (post approval changes).

The aim of this course is to present various aspects of the biowaiver approach, currently used by the EMA and US-FDA, and the strategy of development based on biowaivers. This course is illustrated by case studies that illustrate how to use biowaivers and impact on regulatory submission decision-making.