on the whole organism, since these cells are separated from their biological

environment.

In vitro models including organ-on-a-chip architecture ensure progress in this

field. Cells cultured in microfluidic chip are assumed in the ‘organ-on-a-chip’. The

chip generates artificial organs by simulating bioactivities, dynamics, and physio-

logical behaviour of organs or organ systems. So far, multiple cell lines have been

used for each artificial organ (Nelson and Bissell 2006). The most used cell lines for

the lungs are 16HBE, Calu-3, A549, and NHBE, while the most used cell lines for

the liver are Hep 3B, HepG2, and TPH1 (Nikolic et al. 2018; Langhans 2018). They

demonstrated significance of extracellular matrix in cell performance and are used

widely in culturing cells in 3D systems (Nikolic et al. 2018). Choosing the right

in vitro biological model in the different phases of drug discovery (Fig. 6.1)

establishes a solid foundation for the entire research and development process, and

combining insights from advanced in vitro and in silico methods early in drug

development will increase clinical success rates. Rather than using the traditional

‘bench to bedside’ method, researchers should begin at the bedside, where patient

characteristics, tissue type, and physiological goals are well defined. As a result,

researchers will be able to reverse engineer the drug production pipeline and make

more informed decisions about which biological models to employ. Using an

integrated approach to build in vitro biological model systems, researchers can

obtain more accurate results while saving time and money.

A study conducted by Pan et al. reported results of preclinical studies for

155 drugs that were progressed to clinical studies on humans as part of the regulatory

approval steps. Out of 155, 27 drugs were accepted as monotherapy for treatment of

lung cancer, but 128 drugs declined at some point during clinical trial (Pan et al.

2020). Despite their limited predictability, animal models are still the favoured

approach in drug safety studies. Numerous drugs previously found ineffective in

Fig. 6.1 Illustration of application of in vitro models for different phases of drug research

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G. Aggarwal et al.