Has BCS (Biopharmaceutics Classification System) been a Futile Exercise?

It appears so.

BCS is an approach which has been propagated to reduce the burden of pharmaceutical product evaluations and their regulatory approval using drug dissolution testing instead of in vivo (bioavailability/bioequivalence) testing.

It should be noted that in reality the BCS concept was introduced to facilitate success in establishing IVIVC, which in general had shown poor, or no, success.

The underlying principle of BCS is that if drugs are classified into classes based on their aqueous solubilities and absorptions or permeabilities through the GI tract, then establishing IVIVC may be possible. It is, therefore, important to note that the concept of BCS was introduced to increase the chances of IVIVC success.

For BCS, drugs are divided into four classes having the characteristics of: (I) High solubility and high permeability; (II) Low solubility and high permeability; (III) High solubility and low permeability; (IV) Low solubility and low permeability. As per BCS approach, for drugs which would fall in the low permeability category i.e. classes III and IV, it would be unlikely to achieve successful IVIVC as drug dissolution testing does not relate to permeability. Thus, success of IVIVC may not be possible for the drugs of these classes. The drugs in class I are also considered as poor candidates for a successful IVIVC as these drugs would often dissolve so fast that they may overwhelm the absorption system. Therefore, the drugs in the class II (low solubility and high permeability) and drugs of class I, where release would be manipulated so that drugs appear as slow dissolving (e.g. extended-released type) would have the potential to achieve successful IVIVC. It is important to note that in principle BCS would support potential success of IVIVC with only class II type drugs. However, reported success of IVIVC for drugs in class II has also been limited, (perhaps because of mismatch of in vitro and in vivo environments, see link) and one should be cautious when describing the BCS as a success or useful practice. Thus, the extension of BCS in developing IVIVC and its usefulness in regulatory environment should be considered with care.

On the other hand, there are Guidances available which suggests that the use of the BCS concept for bio-waivers, meaning products may be evaluated using in vitro drug dissolution tests only without in vivo testing. First of all, these Guidances are applicable for products of drugs in class I only, where generally it is recognised that the achieving IVIVC would be highly unlikely based on the BCS concept as explained above. Moreover, there are other conditions as well which these drugs and their product must also meet. For example, products must be of immediate release type and the products must also release the drug very quickly, generally in less than 30 minutes. In essence, the products for which bio-waiver may be considered should be such that they should have drugs which would be released and dissolve quickly. The assumption here is that the human body will consider these products equivalent to solution products. It is obvious from this discussion that the BCS which intended for developing IVIVC plays a limited role in describing bio-waiver criteria for this particular class of drug where no IVIVC is expected.

It may, therefore, be concluded that BCS had been of limited use in facilitating IVIVC, application of dissolution testing in lieu of in vivo testing and/or reducing regulatory burden.

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