To qualify for biowaiver application under the EMA guideline, drugs must be considered noncritical in terms of therapeutic range.Īdditionally, Class I drugs must not include excipients that are suspected of having any relevant impact on BA and Class III drugs must use excipients that are qualitatively the same and quantitatively very similar to those of reference products. In considering biowaiver applications, EMA places more importance on solubility than permeability in vitro permeability data is accepted only in support of clinical data. Under the latest version of EMA guidance (issued in 2010), IR oral dosage forms that demonstrate rapid dissolution and are highly soluble (i.e.Ĭlass I or III) may be eligible to waive the in vivo BE requirement. Others have suggested that dissolution requirements be made less restrictive. More recently, the BCS has been used as an exemplar of FDAs Critical Path Initiative efforts to employ more science-driven approaches to streamlining clinical trials.Įxperts have proposed extending biowaiver eligibility to Class II drugs that are poorly soluble weak acids and to Class III drugs that exhibit rapid dissolution. The guidance provides recommended approaches for classifying an IR oral drug product and determining its dissolution characteristics. In 2000, the US Food and Drug Administration (FDA) set forth a guide for sponsors to justify requests to waive in vivo BA andor BE study requirements for IR solid oral dosage forms based on BCS criteria. The evaluation of these properties can be performed in vitro, therefore avoiding expensive and time-consuming testing in humans.īCS was originally used to grant biowaivers for scale-up and post-approval changes for drug products, but was later extended to the approval of new generic products. International differences in BABE-related guidelines should be reconciled in order to realise the potential cost benefits and time savings of the Biopharmaceutics Classification System.ĭeveloped by Amidon and colleagues, the system classifies IR solid oral dosage forms on the basis of solubility and permeability parameters (when combined with dissolution testing).Īccording to this schema, drug substances are categorised as having either rapid or slow in vitro dissolution and then classified based on aqueous solubility and intestinal permeability of the active pharmaceutical ingredient (API).
What role BCS should play in the consideration of biowaivers has garnered the attention of regulatory authorities in recent years. By providing a basis for avoiding unnecessary in vivo studies, BCS helps significantly reduce the cost and time of developing drug products.īCS has gained importance worldwide as a drug product regulation tool the system has been formally adopted by the U.S.įood and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) (with some modifications) as a means to establish technical standards for waiving bioavailability (BA) and bioequivalence (BE) testing requirements for oral drugs.
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