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FDA nanomaterial draft guidance means pointless extra regulation, say experts

By Natalie Morrison+, 22-Nov-2011

Related topics: Delivery technologies, Excipients, raw materials and intermediates, QA/QC, Tabletting, coating & ancillary equipment, Regulations, Ingredients

FDA draft guidance defines nanoparticles too broadly and could result in APIs being categorised as nanomaterials, industry said.

Commenters on the US Food and Drug Administration (FDA) draft guidance said the definition of nano is too broad to be workable. In its current form BIO (Biotechnology Industry Organization) fears the guidance could categorise many products as nanomaterials.

Andrew Emmett, managing director of science and regulatory affairs at BIO, wrote: “It is not sufficiently clear what counts as a product involving the application of nanotechnology, and how the Draft Guidance should be interpreted with respect to pharmaceuticals in particular.

He added that the guidance should specify practical limits for common operations like jet milling, which can result in a certain percentage of particles in the nanoscale. “It should not result in the active pharmaceutical ingredient (API) product being categorized as a nanomaterial.”

Throughout the replies, a stand-out theme was that the FDA establishing an “upper limit” of 1,000 nm would lead to an overly-expansive umbrella term for what contains nanoparticles, and what is nanoparticle technology.

Several respondents voiced their fears that, if put into action, the guidance could lead to unnecessary extra regulatory pathways, and a call for potentially needless extra screening processes for manufacturers.

“In the pharmaceutical area, a variety of very different pharmaceutical systems or products such as (mixed) micelles, polymer systems (dendrimers), liposomes, (modified) therapeutic monoclonal antibodies, emulsions, suspensions, and crystalline particles, contain nanoscale particles, but most are not considered to be ‘nanomaterials’”, Emmett said

Injectables concerns

Celegene added that relevant criteria should be used when applying the first reference point of approximately 1 to 100 nm (with upper limit of 1,000), giving the example of injectables made using nanotechnology.

In its reply, Celegene stated: “FDA should consider use of 220 nm for the first reference point analysis of injectable products, rather than the more arbitrary standard of 100 nm.”

The firm cites papers which look at nanomaterials designed for in vivo absorption, in which 220 nm reflects the windows between liver or spleen cells that constitute part of the mononuclear phagocytic system.

It also considers nanomaterials for in vivo absorption under sterile conditions, which puts them at increased risk of being damaged.

Similarly CPHA (Consumer Products Healthcare Association) insisted evaluation should be on a “case-by-case” basis, instead of scrutinising everything that falls under the FDA’s nanomaterials umbrella.

Working on a global scale

In a bid to implement the guidance successfully, correspondents urged the FDA to work on a global scale.

SOCMA (Society of Chemical Manufacturers and Affiliates) suggested the FDA look to regulatory boards in other countries who have been successful.

The SOCMA Nanotechnology Coalition letter stated: “The Coalition urges FDA to consider global efforts to define nanomaterials and recognize the significant efforts of international standards-setting bodies regarding nanoscale materials.”

Whilst IPEC (International Pharmaceutical Excipients Council of the Americas) insisted working with regulatory boards in other countries was crucial, “otherwise it will be difficult for global companies to fully take advantage of the concepts this guidance provides.”