Information Technology Reference
In-Depth Information
6.8 Biowaiver considerations
The role of biowaivers in the drug approval process has been emphasized
since the introduction of BCS (Amidon et al., 1995) and the release of
FDA guidance on waiver of
in vivo
bioavailability and BE studies (US
Food and Drug Adminstration, 2000). In this context, the term biowaiver
refers to the situations in which
in vivo
BE studies can be substituted with
the relevant
in vitro
data. The main premise, when adopting the biowaiver
concept, was to reduce time and costs, and to offer benefi ts in terms of
ethical considerations. The most common type of biowaiver adopted by
the regulatory authorities includes the application of the BCS-based
scheme (similar or rapid/very rapid dissolution profi les of the test and
reference product in pH 1.2, 4.5, and 6.8 media) or the application of
IVIVC. According to the FDA, biowaivers for IR drug products may be
requested solely in the cases of highly soluble and highly permeable
substances (BCS class I) when the drug product is (very) rapidly dissolving
and exhibits similar dissolution profi le to the reference product, while the
IVIVC-based approach has been narrowed down to applications for XR
products (US Food and Drug Administration, 2000, 1997). The EMA
and WHO issued guidelines widened the eligibility for biowaiver to some
BCS class III (eligible if very rapidly dissolving) (European Medicines
Agency, 2010; WHO Expert Committee on Specifi cations for
Pharmaceutical Preparations, 2006) and BCS class II drugs (eligible for
biowaiver if the dose-to-solubility ratio at pH 6.8 is 250 mL or less and
high permeability is at 85% absorbed) (WHO Expert Committee on
Specifi cations for Pharmaceutical Preparations, 2006). Also, it was
pointed out that the biowaiver concept concerning BCS II and III drugs
should be further relaxed (e.g. BCS class II drugs eligible for biowaiver
under the assumption that the drug dissolves completely during the GI
passage (Yu et al., 2002), and BCS class III compounds eligible if rapidly
dissolving (Tsdume and Amidon, 2010)).
Several examples from the literature describe how GIST can be used to
identify BCS class(es) of drugs eligible for biowaiver. In the previously
mentioned
in vitro-in silico
study of GLK IR tablets, simulation results
demonstrated that differences in GLK
in vitro
dissolution kinetics, such
as 85% drug dissolved within the 15 to 60 min time frame, are not
expected to refl ect on the
in vivo
PK profi le. These results support the
assumption that, in the case of BCS class II drugs, complete
in vivo
dissolution might occur at later time points than for highly soluble BCS
class I drugs. This would allow wider biorelevant
in vitro
dissolution
specifi cation, than very rapid/rapid
in vitro
dissolution, to be set. In
Search WWH ::
Custom Search