Regulating Nanomedicine – Can the FDA Handle It?

Abstract

There is enormous excitement and expectation surrounding the multidisciplinary field of nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry. This is especially true in the design, formulation and delivery of therapeutics. Currently, nanomedicine is poised at a critical stage. However, regulatory guidance in this area is generally lacking and critically needed to provide clarity and legal certainty to manufacturers, policymakers, healthcare providers as well as public. There are hundreds, if not thousands, of nanoproducts on the market for human use but little is known of their health risks, safety data and toxicity profiles. Less is known of nanoproducts that are released into the environment and that come in contact with humans. These nanoproducts, whether they are a drug, device, biologic or combination of any of these, are creating challenges for the Food and Drug Administration (FDA), as regulators struggle to accumulate data and formulate testing criteria to ensure development of safe and efficacious nanoproducts (products incorporating nanoscale technologies). Evidence continues to mount that many nanoproducts inherently posses novel size-based properties and toxicity profiles. Yet, this scientific fact has been generally ignored by the FDA and the agency continues to adopt a precautionary approach to the issue in hopes of countering future potential negative public opinion. As a result, the FDA has simply maintained the status quo with regard to its regulatory policies pertaining to nanomedicine. Therefore, there are no specific laws or mechanisms in place for oversight of nanomedicine and the FDA continues to treat nanoproducts as substantially equivalent ("bioequivalent") to their bulk counterparts. So, for now nanoproducts submitted for FDA review will continue to be subjected to an uncertain regulatory pathway. Such regulatory uncertainty could negatively impact venture funding, stifle nanomedicine research and development (R&D) and erode public acceptance of nanoproducts. The end-result of this could be a delay or loss of commercialized nanoproducts. Whether the FDA eventually creates new regulations, tweaks existing ones or establishes a new regulatory center to handle nanoproducts, for the time being it should at least look at nanoproducts on a case-by-case basis. The FDA should not attempt regulation of nanomedicine by applying existing statutes alone, especially where scientific evidence suggests otherwise. Incorporating nanomedicine regulation into the current regulatory scheme is a poor idea. Regulation of nanomedicine must balance innovation and R&D with the principle of ensuring maximum public health protection and safety.

The bio-corona and its impact on nanomaterial toxicity

“…Though, besides the current enthusiasm for nanotechnology, the wide use of nanomaterials may pose unknown risks to human health and the environment (7,(17)(18)(19)(20)(21). Particularly, experiences with 'new' materials in the past, such as asbestos, have sensitized the public also for the risk of 'similar' NM, such as single-walled carbon nanotubes (SWCNT).…”

“…Issues relevant to pulmonary toxicity of SWCNT, their direct cytotoxic effects, their ability to cause inflammation, and induce oxidative stress upon inhalation are currently actively investigated (7,(17)(18)(19)(20)(21). As NPs are able to highjack the endocytosis machinery and may enter almost any cell type (22), their recognition and engulfment by macrophages, phagocytosis and biodistribution in tissues and the circulation are still under intense discussion (7,(17)(18)(19)(20)(21). Once inside a cell, NPs may cause adverse effects (23) resulting even in permanent cell damage (24,25).…”

“…The discussion about nanosafety upon intended as well as unintended exposure of humans and the environment is thus clearly important and still ongoing (7,(17)(18)(19)(20)(21). As society at large is now aware of the use of NM in ever growing quantities in consumer products and their presence in the environment, critical interest in the impact of this emerging technology has grown.…”

Pharmaceutical characterization of solid and dispersed carbon nanotubes as nanoexcipients

“…13,14 While no additional guidelines or regulatory requirements have been released for formulations containing nanoparticles, thorough physicochemical characterization of all constituents in these products is essential for FDA approval. [15][16][17] Basic physicochemical characterization includes, but is not limited to, characterization of structure, composition, quality, purity, and reproducibility of nanoparticle synthesis.…”

Towards a computational prediction of nanoparticle pharmacokinetics and distribution

“…Since efficacy and toxicity of therapies can be influenced by nanoparticle distribution [4], the appropriateness of existing regulation for nanomedicines has been the subject of significant recent debate [5,6]. Consequently, understanding the interactions between nanomaterials and the human body is of great importance to efficient development of safe and effective new drug delivery systems, and requires a rigorous understanding of how the physical properties of the materials superimpose upon the relevant anatomy, physiology and pharmacology.…”