The problem with gaps.

The problem with gaps.

After writing about gap analysis for the Pharma of the Future? blog, I went in search of an example that would illustrate the problem of defining “gaps” and stumbled on a piece called Reading and Guilty Pleasure in the New York Times. The writer, Gary Gutting, describes 2 assumptions underlying the concept of a guilty pleasure: some books are objectively inferior to others, and “better” books are generally not very enjoyable. So, are “better” books actually better? Gutting says that in discussions of this sort, people will often adopt a relativist position:

Mind the gap

Mind the gap

I was talking with a Program Director the other day about an upcoming regulatory filing. She was rightly proud of the clinical pharmacology work that had been completed, but she was also anxious about possible holes in the package. As we talked, I thought about how gap analyses have changed over the years, particularly since modeling and simulation results have come to play a larger part in the Clinical Pharmacology Summary in NDA submissions.

The Use of Modeling Tools to Drive Efficient Oral Product Design

The Use of Modeling Tools to Drive Efficient Oral Product Design

Authors: Mathias NR, Crison J
Publication: AAPS J
Software: GastroPlus®

Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active...

Preclinical Assessment of the Absorption and Disposition of the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor GDC-0980 and Prediction of Its Pharmacokinetics and Efficacy in Human

Preclinical Assessment of the Absorption and Disposition of the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor GDC-0980 and Prediction of Its Pharmacokinetics and Efficacy in Human

Publication: Drug Metab Dispos
Software: GastroPlus®

The objectives of these studies were to characterize the absorption and disposition of GDC-0980 and assess its efficacy in an MCF7-neo/HER2 human breast cancer xenograft model in immunocompromised mice.

Application of PBPK modeling to predict human intestinal metabolism of CYP3A substrates – An evaluation and case study using GastroPlus™

Application of PBPK modeling to predict human intestinal metabolism of CYP3A substrates – An evaluation and case study using GastroPlus™

Publication: Eur J Pharm Sci
Software: GastroPlus®

First pass metabolism in the intestinal mucosa is a determinant of oral bioavailability of CYP3A substrates and so the prediction of intestinal availability (Fg) of potential drug candidates is important.

Predicting feasibility and characterizing performance of extended-release formulations using physiologically based pharmacokinetic modeling

Predicting feasibility and characterizing performance of extended-release formulations using physiologically based pharmacokinetic modeling

Publication: Ther Deliv
Software: GastroPlus®

This review presents nine case studies where physiologically based pharmacokinetic modeling has been used in the design and development of extended-release formulations.

An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury

An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury

Publication: J Pharmacol Exp Ther
Keywords: apap, DILI
Software: DILIsym®

N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning; standard 72-h oral or 21-h intravenous protocols are most frequently used.

Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products

Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products

Publication: Molecules
Software: ADMET Predictor®

Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison...

Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

Authors: Saibi Y, Sato H, Tachiki H
Publication: AAPS PharmSciTech
Software: GastroPlus®

The present study was aimed to predict the absorption profile of a risperidone immediate release tablet (IR) and to develop the level A in vitro–in vivo correlation (IVIVC) of the drug using...

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen

Publication: Biopharm Drug Dispos
Software: GastroPlus®

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivobioavailability and bioequivalence studies for immediate-release solid oral...