formulations, usually indicating high prognostic power (Schwartz et al. 1996; Singh

2014; Singh et al. 2017a, b).

18.8

Regulatory Perspectives on Drug Nanoconstructs

Reducing the size of particles to nanoscale is considered as an inimitable attribute, as

the majority of inherent properties of the matter get altered remarkably at this scale.

These newer attributes often significantly impact the quality, efficacy and safety of

the therapeutic drug product. A nanomedicinal product, for example, may have a

unique surface coating or functional moieties, including ligands, peptides,

antibodies, etc., that avert its interaction with body immune cells, so that the drug

molecule circulates in a bloodstream for prolonged time periods, till it reaches the

targeted tumour tissues. The potential to target particular tissues of body, or circum-

vent many others, can markedly reduce the possible risk(s) of adverse effects and

toxicity issues to non-target sites and potentially improve the success rate of the

therapeutic regimen (Prud’homme and Svenson 2012; De Crozals et al. 2016). This

is one of the major concerns for all the shareholders, be it regulators, scientists or the

consumers. Today, nanomedicine encompasses a broad diversity of innovative

nanostructured drug delivery systems as well as devices for preventive, therapeutic,

diagnostic or theranostic applications. Management of nanotechnology-based thera-

peutics by the regulatory bodies for the past few years has, consequently, been

containing different therapeutics, vaccines, biotechnological products, cosmetics,

foods and medical devices (Re et al. 2012; Nanda et al. 2015; Beg et al. 2017a, b).

The toxicity as well as safety concerns should be taken into account much earlier to

the marketing of nanotechnology-based therapeutics for ostensible amelioration in

the quality of health. As the existing know-how of the toxicological aspects of bulk

ingredients may be insufficient for the reliable estimation of toxic forms of

nanocarriers, an inclusive proposal to understand the nanotoxicity has been felt as

an acute need of the hour, since years (Arora et al. 2012). An evolving body of

studies reveals the impacts, if at all, these nanoconstructs will put forth on environ-

ment, health and safety concerns (Wang et al. 2011; Chopra et al. 2015).

In 2013, a categorization system was introduced for describing the toxicological

aspects of nanostructures, on the basis of their particle size and biodegradability. The

Class I nanostructures (biodegradable systems with the size range of 100–1000 nm)

are designated with low risk and are demarcated with green colour. Class II

nanostructures are non-biodegradable and are greater than 100 nm, and Class III

particles are biodegradable having their sizes less than 100 nm. As both of the Class

II and III nanostructures tend to exhibit medium risk, these are demarcated with

yellow colour. Class IV nanostructures (non-biodegradable with size less than

100 nm), on the contrary, are related with high-risk toxicity and are marked with

red colour.

In spite of these specific characteristics of nanoconstructs, the regulatory

procedures entailed in approval of nanopharmaceutical drug products by the federal

agencies, like the US-FDA, have generally been quite analogous to those suggested

18

QbD-Steered Systematic Development of Drug Delivery Nanoconstructs:. . .

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