Introduction
The International Conference on Harmonization (ICH) M9: Biopharmaceutics Classification System-based Biowaivers,1,2 was adopted in mid-June 2016. A biowaiver allows for in vitro testing to be used in lieu of in vivo bioavailability and/or bioequivalence studies to facilitate product approval, where solubility and permeability are not expected to impede bioavailability. ICH M9 will therefore minimize unnecessary in vivo studies in man and allow greater public access to vital medicines. However, this approach is not always universally aligned or recognized.
The Role of Biowaivers
In certain cases regulatory applications using biowaivers are permissible. Submissions can be either based on BCS, in vitro - in vivo correlation (IVIVC), in vitro - in vivo relationship (IVIVR) or simply on an in vitro dissolution profile comparison. Examples of the BCS, IVIVC or IVIVR biowaiver approach include:
- in support of generic product entry versus the innovator product
- in support of regulatory submission, i.e. changing the product type during development (capsules to tablets, etc.)
- in support of over-encapsulated comparator products, that are often used in pivotal clinical studies
- in support of bridging between the product used in pivotal clinical studies and the ‘to be marketed’ commercial product
- in support of product line extensions (PLEs) for different clinical populations, i.e. pediatric or geriatric products
- in support of post-approval changes
History and Evolution of BCS
The BCS was introduced in 19954 to facilitate the introduction of biowaivers into the regulatory lexicon. The BCS scheme is a 4-box model for drug product assessment based on an evaluation of the drug solubility and permeability. There are four classifications: BCS class 1 (highly soluble and highly permeable), class 2 (poorly soluble and highly permeable), BCS class 3 (highly soluble and poorly permeable) and BCS class 4 (poorly soluble and poorly permeable).
