The use of bioreactors as in vitro models in pharmaceutical research

• Published in: Drug discovery today Vol. 18; no. 19-20; pp. 922 - 935
• Main Authors: Ginai, Maaria, Elsby, Robert, Hewitt, Christopher J., Surry, Dominic, Fenner, Katherine, Coopman, Karen
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2013
• Subjects: Animals; Bioartificial Organs - trends; Biomedical Research; Bioreactors; Humans; Models, Biological; Technology, Pharmaceutical - methods; Technology, Pharmaceutical - trends
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2013.05.016

•The need for more reliable in vitro methods during new chemical and biological entity (NCE and NBE) development is stressed.•The advantages of dynamic 3D cellular systems over current 2D systems are explained.•Examples of the current use of bioreactors as in vitro models are given.•The use of bioartificial kidney devices in the clinic is discussed.•Progression from these into an in vitro model is proposed. 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. We discuss the development of dynamic 3D bioreactor-based systems as in vitro models for use in DMPK studies.