REVIEWS Drug Discovery Today  Volume 18, Numbers 19/20  October 2013 We discuss the development of dynamic 3D bioreactor-based systems as in vitro models for use in DMPK studies. The use of bioreactors as in vitro models in pharmaceutical research Maaria Ginai 1 , Robert Elsby 2 , Christopher J. Hewitt 1 , Dominic Surry 2 , Katherine Fenner 2 and Karen Coopman 1 1 Centre for Biological Engineering, Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK 2 In vitro In Silico ADME, Global DMPK, AstraZeneca Research and Development, Alderley Park, Mereside, Macclesfield SK10 4TG, UK Bringing a new drug to market is costly in terms of capital and time investments, and any development issues encountered during late-stage clinical trials can often be the result of in vitro–in vivo extrapolations (IVIVE) not accurately reflecting clinical outcome. In the discipline of drug metabolism and pharmacokinetics (DMPK), current in vitro cellular methods do not provide the 3D structure and function of organs found in vivo; therefore, new dynamic methods need to be established to aid improvement of IVIVE. In this review, we highlight the importance of model progression into dynamic systems for use within drug development, focusing on devices developed currently in the areas of the liver and blood– brain barrier (BBB), and the potential to develop models for other organ systems, such as the kidney. Currently, the pharmaceutical industry balances the stringent testing of drugs and products against soaring costs and return on investments risks. Bringing a new drug to market will, presently, on average cost US$1.3 billion over 12 years [1,2] with preclinical in vitro testing consuming approximately half of the total development time [2]. Moreover, many new chemical and biological entities (NCEs and NBEs, respectively) that fail late-stage human testing provide evidence for the fact that pharmacological and toxicity data from in vitro cell-based assays are not always predictive of the clinical situation [3]. Owing to these financial and time commitments, there is great emphasis within the industry on the development of newer and more reliable in vitro and preclinical methods to accompany or replace the existing methods of NCE–NBE investigations. In vitro models, particularly cell-based versions, are used in various areas of drug discovery, such as target identification and validation using disease models, compound screening and basic cytotoxicity using static cultures, through to absorption, distribution, metabolism, excretion and toxicology (ADMET) studies on lead compounds. Although high-throughput cell-based assays have revolutionised the efficiency and speed at which compounds can be screened, ADMET models ideally should be an accurate representation of the physiological or pathophysiological Reviews  FOUNDATION REVIEW Maaria Ginai is currently studying a BBSRC CASE- funded PhD at the Centre for Biological Engineering at Loughborough University (UK) in the area of bioartifi- cial device progression to in vitro models for use in the pharmaceutical industry. Her PhD is supported by AstraZeneca. She graduated with a first-class Bachelors degree with honours in bio- medical science from the University of Kent (UK) in 2010. Christopher J. Hewitt is the director of the £7.3 M EPSRC Doctoral Training Centre in Regenerative Medicine and co-founder of the £2 M Centre for Bio- logical Engineering at Loughborough University (UK). He also leads the Cell Technologies research group, whose work spans the engineering–life science interface seeking to understand the interaction of the organism with the engineering environment within such diverse areas as microbial fermentation, bio- transformation, cell culture and, mostly recently, regenerative medicine bioprocessing. Christopher has a first-Class Bachelors degree in biology from Royal Holloway College, University of London (UK) and a PhD in chemical engineering from the University of Birmingham (UK). Karen Coopman was appointed to a lectureship at Loughborough University, where she is the operations manager of the EPSRC- funded Doctoral Training Centre in Regenerative Medicine. She co-leads the Cell Technologies research group within the Centre for Biological Engineering of the University, and is cur- rently a member of the Early Career Forum in Manufacturing Research of the EPSRC. The over- arching themes of Karen’s research are the manu- facture of cellular therapies and the use of cells in the drug discovery process. Karen has a first-class Bachelors degree in pharmacology from the Univer- sity of Bristol (UK) and a PhD from the Department of Pharmacy and Pharmacology at the University of Bath (UK). Corresponding author:. Coopman, K. (k.coopman@lboro.ac.uk) 922 www.drugdiscoverytoday.com 1359-6446/06/$ - see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2013.05.016