Early Development Challenges for Drug Products Containing Nanomaterials

Abstract

The vast majority of drug product candidates in early development fail to progress to clinics. This is true for products containing nanomaterials just as for other types of pharmaceuticals. Early development pathways should therefore place high priority on experiments that help candidates fail faster and less expensively. Nanomedicines fail for many reasons, but some are more avoidable than others. Some of the points of failure are not considerations in the development of small molecules or biopharmaceuticals, and so may be unexpected, even to those with previous experience bringing drug products to the clinic. This article reviews experiments that have proven useful in providing "go/no-go" decision-making data for nanomedicines in early preclinical development. Of course, the specifics depend on the particulars of the drug product and the nanomaterial type, and not every product shares the same development pathway or the same potential points of failure. Here, we focus on challenges that differ from those in the development of traditional small molecule therapeutics, and on experiments that reveal deficiencies that can only be corrected by essentially starting over-altering the nanomedicine to an extent that all previous characterization and proof-of-concept testing must be repeated. Conducting these experiments early in the development process can save significant resources and time and allow developers to focus on derisked candidates with a greater likelihood of ultimate success.

Nano based drug delivery systems: recent developments and future prospects

“…After approval in these three phases the IND can be filed by the FDA to request endorsement of the new nanomedicine or nano drug delivery systems. However, this approach to nanomedicine regulation has been extensively questioned [ 204 , 246 , 252 ].…”

“…Due to the rapid development of nanotechnology as well as its potential use of nanomedicine, a reformed and more integrated regulatory approach is urgently required. In this regard, country governments must come together to develop new protocols that must be specific and sufficiently rigorous to address any safety concerns, thus ensuring the release of safe and beneficial nanomedicine for patients [ 204 , 252 , 253 ].…”

Challenges of in vitro characterization of nonbiological complex drugs: Example of parenteral preparations with liposomal drug carriers

“…Definisanje i procena kritičnih svojstava kvaliteta je od izuzetnog značaja za nebiološke kompleksne lekove, kako bi se osigurala njihova bezbednost i terapijska efikasnost. Procena kvaliteta ovih lekova zahteva multidisciplinaran pristup, kako bi se utvrdile njihove fizičkohemijske karakteristike, in vitro i in vivo ponašanje, uz dodatna intenzivna istraživanja na razvoju novih metoda koje bi dodatno doprinele karakterizaciji ovih lekova (7,9,14,15 Primena odgovarajućih metoda karakterizacije od posebnog je značaja prilikom podnošenja zahteva za registraciju inovativnih nebioloških kompleksnih i njima sličnih lekova (tzv. "nanosimilara"), odnosno lekova za koje se tvdi da su slični referentim (originatorskim/inovativnim) nanolekovima kojima je istekla patentna zaštita (15).…”

Equivalence of complex drug products: advances in and challenges for current regulatory frameworks

“…However, novel techniques for evaluating complex drug similarity are becoming available at a rapid pace. For example, advanced methods recently developed by the Nanotechnology Characterization Laboratory may accelerate the understanding of which parameters are part of the critical attributes and thereby potentially speed up development of follow‐on versions of nanoparticle‐based products.…”