Biopharmaceutics classification system (BCS) as a framework for selective approach to bioavailability/bioequivalence (BA/BE) investigation

Abstract

One of fundamental investigations, that pharmaceutical industry is expected to conduct during development of pharmaceutical formulation in order to prove its efficiency and safety, is bioavailability (BA), or bioequivalence (BE) assessment. Traditional approach to this investigation entails strictly controlled, expensive and time consuming study in humans. The potential for considering drugs' in vivo behavior has been extended and new selective approach has been set by development of Biopharmaceutics Classification System (BCS) and evaluation of drug absorption according to solubility and permeability properties of the drug, as well as its dissolution from pharmaceutical preparation. Manufacturers are particularly interested in creating criteria based on BCS concept for granting waiver of BA/BE studies for Immediate Release Products (IRP), aiming for reduction of time and cost of drug development process. These criteria have been discussed at many experts' meetings lately, and regulatory agencies are expected in near future to consider proposals for changes in regulative requirements according to the results from practice. If some of them were accepted, BCS would become even more significant as a powerful tool in drug and pharmaceutical preparation development process.

U osnovi ispitivanja, koja proizvođač sprovodi tokom razvoja formulacije farmaceutskog preparata u cilju dokazivanja efikasnosti i bezbednosti, nalazi se ispitivanje biološke raspoloživosti (BR), odnosno relativne biološke raspoloživosti/biološke ekvivalentnosti (BE) preparata. Tradicionalni pristup ovom ispitivanju podrazumeva strogo kontrolisano, skupo i dugotrajno in vivo ispitivanje u ljudi. Razvojem biofarmaceutskog sistema klasifikacije (BSK) i procenom resorpcije lekovitih supstanci na osnovu njihove rastvorljivosti, permeabilnosti kroz membrane i brzine rastvaranja iz farmaceutskog preparata, proširene su mogućnosti za sagledavanje in vivo ponašanja lekova i postavljena osnova za savremeni, selektivni pristup ispitivanju BR/BE. Za proizvođače je od posebne važnosti upotreba BSK-a u postavljanju kriterijuma za oslobađanje konvencionalnih preparata od ispitivanja BR/BE (waiver of BA/BE studies), sa ciljem uštede vremena i novca u procesu razvoja leka. Ovi kriterijumi su poslednjih godina predmet brojnih stručnih rasprava i u bliskoj budućnosti očekuje se da će regulatorne agencije razmotriti predloge za izmene u regulativi zasnovane na rezultatima iz prakse. Usvajanjem nekih od njih, BSK bi dobio još veći značaj kao moćno sredstvo u procesu razvoja lekovite supstance i farmaceutskih preparata.