Biowaiver for Immediate Release Solid Oral Dosage Form: A General Overview

Biowaiver is a waiver of in vivo bioavailability or equivalence by in vitro studies. It has been regarded as an official approval of the waiver for conducting a bioequivalence study in the context of an application for drug approval process. Food and Drug Administration (FDA), World Health Organization (WHO), European Union on Medicine Agency (EUMA) has allowed certain Active Pharmaceutical Ingredients (APIs) for biowaiver base on the Biopharmaceutical Classification System (BCS). The BCS is a scientific approach for classifying drug substances based on their dose/solubility ratio and intestinal permeability. Biowaiver is possible for APIs of BCS I and some APIs of BCS II and BCS III. This simpler easily implemented in vitro studies ensure effective clinical performance. The present review aims to discuss the requirement and different regulator guidance on biowaiver for immediate release solid oral dosage form. Tekendra Pant Deurali Janta Pharmaceuticals Pvt Ltd, Kathmandu, Nepal Submission: 23 July 2018 Accepted: 30 July 2018 Published: 30 August 2018 www.ijppr. humanjournals.com Citation: Tekendra Pant et al. Ijppr.Human, 2018; Vol. 13 (1): 245-250. 246 INTRODUCTION Over the past many years, dissolution testing has evolved into a powerful tool for characterizing the quality of oral pharmaceuticals product. The dissolution test, at first exclusively a quality control test, is now emerging as a surrogate equivalence test for certain categories of orally administered pharmaceutical products (WHO, 2006). Biowaiver means to get a waive off for doing bioavailability and bioequivalence studies. In 1995 the Department of human health, federal drug agency of the United States of America (HHS-FDA) instigated the BCS with the aim of granting – so-called biowaiver for scale-up and post-approval changes(SUPAC)(WHO, 2005) but later, the biowaiver principle was extended to the approval of the generic products(Dahan et al., 2009 ). It is considered as the waiver of clinical bioequivalence studies (Dreesman et al., 2012). Instead of conducting expensive and time-consuming in vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceuticals products are equivalent. BCS was proposed in 1995 by Amidon et al. ((Dahan et al., 2009), it is a scientific work which divides APIs (Active Pharmaceutical Ingredients) into four groups (Yu et al., 2002) (Table 1). The solubility classification of a drug in the BCS is based on the highest dose strength of an immediate release. A drug substance is considered highly soluble when the highest strength is soluble in 250 ml or less aqueous media over the pH range 1-7, otherwise the drug substances are considered to be poorly soluble((Dahan et al, 2009 ), the permeability classification of drug substance is based on the extent of intestinal absorption of a drug substances in human or indirectly on the measurements of a mass transfer across the luminal intestinal membrane, a drug substance is considered highly permeable when the extent of intestinal absorption is determined to be 90 % or higher, otherwise poorly permeable. WHO considered solubility range of pH1.2-6.8 and 85% or more for the permeability (WHO, 2006). www.ijppr. humanjournals.com Citation: Tekendra Pant et al. Ijppr.Human, 2018; Vol. 13 (1): 245-250. 247 Table 1: BCS classification based on aqueous solubility and intestinal permeability BCS I High solubility High permeability BCS II Low solubility High permeability BCS III High solubility Low permeability BCS IV Low solubility Low permeability The requirement for biowaiver (Rohilla et al, 2012): (a)The drugs should have high solubility and high permeability according to BCS. However, other classification systems are part of current investigations. (b) Dissolution Test in 3 different media which are: Buffer pH 1.2, simulated gastric fluid (SGF) without enzymes or 0.1N HCl, Buffer pH 4.5 and Buffer pH 6.8 or simulated intestinal fluid (SIF) without enzymes, all in 900 ml and at 37°C. (c) Twelve’s samples in each media, paddle rotating at 50 rpm or basket at 100 rpm. (d) Sampling times are 10, 15, 20, 30, 45 and 60 minutes. (e) The profiles of the test and reference products must be similar in all three media. (f) The products are similar if the similarity factor f2 ≥ 50 and both products show ≥ 85% dissolution in 15 min. Following equation is used to calculate f2: f2 = 50 log {[1 + 1/nΣn=1(Rt – Tt) 2]-0.5 x 100} Where, Tt and Rt are percent drug dissolved at each time point for test and reference product, respectively. Different guidance to IR oral dosage form for biowaiver