ICH M9 Guideline in Development on Biopharmaceutics Classification System-Based Biowaivers: An Industrial Perspective from the IQ Consortium

Abstract

In October 2016, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) ICH began efforts to provide recommendations to harmonize guidances for biopharmaceutics classification system (BCS)-based biowaivers. Topics to be addressed included consideration of the dose used to classify solubility, tests, and criteria for establishing highly permeable, dissolution conditions, the influence of excipients, and aspects of product strength. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) is a technically focused organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader R&D community. Its members have substantial expertise in all scientific domains associated with BCS-based waivers and drug product quality, as well as considerable experience in the application of BCS-based biowaivers. The ICH process recognizes that harmonization is achieved through the development of guidelines via a process of scientific consensus with regulatory and industry experts working side-by-side. Thus, to facilitate these efforts and to encourage open and transparent discussion of other perspectives that may exist, IQ offers their perspective on these and related topics.

Global testing of a consensus solubility assessment to enhance robustness of the WHO biopharmaceutical classification system

“…For the remaining six APIs, experimental solubility assessment confirmed the earlier solubility classification based on literature data. However, due the experimental difficulty to directly assess f a in humans, the research community is faced with widespread uncertainty regarding the most appropriate methodology to consistently categorize APIs as “high permeability” or “low permeability” drugs [ 39 ]. Provisional classification of APIs according to the WHO BCS in 2006 [ 6 ] was exclusively based on literature data.…”

Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Brain Levels of Drug in Rat

“…The development of new in vitro and mathematical tools able to predict concentration levels of drugs in humans is extremely interesting for pharmaceutical industries, as they can help avoid failures after huge investments of money, and they can also bypass ethical problems. With this aim, over many years, several researchers have worked on the development of new in vitro dissolution tools or in vitro–in vivo correlations in the field of oral absorption, and biowaivers have been highly legislated [ 30 , 31 , 32 , 33 ]. In terms of CNS medicine, although it is less regulated, the development of new PBPK models has become even more important, due to the difficulties in obtaining new treatments able to cross the BBB.…”

Physiologically Based Biopharmaceutics Modeling to Demonstrate Virtual Bioequivalence and Bioequivalence Safe-space for Ribociclib which has Permeation Rate-controlled Absorption

“…Measured dissolution: In vitro dissolution of one unit of each dosage-form (capsule, tablet BE, tablet commercial) was done using USP 1 basket (for capsule and tablet) and USP 2 paddle apparatus (for tablet) described in USP <711> (N = 12 replicates) 13 under sink conditions. Formulation dissolution kinetics were investigated at pH 1, 2, 4.5 and 6.8 using the same aqueous media as for solubility.…”