CHPA Comments on Draft FDA Guidance on Nanotechnology

Last week, the Consumer Healthcare Products Association (CHPA) submitted comments on the FDA’s draft guidance on nanotechnology, "Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, "  which we posted on before.

CHPA is the not-for-profit association representing the makers of over-the-counter medicines and dietary supplements, and the consumers who rely on these healthcare products. CHPA is one of the oldest trade associations in the United States. Nanotechnology holds great promise for this industry.

CHPA agreed with the FDA that proposing a "definition" for nanotechnology is not a straight forward process; applying a strict, universal definition of nanotechnology to the fields of drug research, drug product development and drug manufacturing would not be, in CHPA's view, an appropriate science-based approach.

Defining a nanomaterial as a structure between 1 and 100 nm, and using this definition to establish new regulations on products containing nano-sized materials, would, they asserted,  erroneously group drug products together to form a new category based on size of ingredients.  Nanotechnology is not a separate drug category, but a technology used to, among other things, generate nanometer-sized ingredients and excipients. Inclusion of nanometer-sized active ingredients or excipients in a drug product does not by itself determine a product's safety and efficacy (i.e. size alone is not itself an indicator of toxicity). 

CHPA agreed that the agency should distinguish between engineered nanomaterials and those
naturally occurring at the nanoscale.  There exist common pharmaceutical ingredients with a long history of use that should not be considered as "engineered nanomaterials" or as agglomerates of nanomaterials but which may have particles whose size naturally falls within this range.

CHPA also noted that NIOSH accurately refers to nanotechnology as the manipulation of matter on a near-atomic scale to produce new structures, materials, and devices.  Nanomaterials are mainly engineered for their novel chemical, physical, and quantum mechanical properties; at the nanometer size, many materials exhibit such unique beneficial properties that may not exist when at the micron size. CHPA argued it is appropriate to include in the description the notion of particles that are deliberately manipulated and controlled at the nanoscale, which also exhibit changes in physical, chemical, or electromagnetic properties, the existence of unique phenomena to enable novel applications.

For example, milling, a beneficial process for the manufacturing of many individual pharmaceutical ingredients, may create particles with a portion of the particle size distribution under 1 micron; however, the chemical properties of the milled ingredient usually do not differ drastically from that of the bulk ingredient.

The agency should give further consideration, said CHPA,  to the possibility that not all materials should be considered equal; each material must be evaluated on a case-by-case basis. For example, soluble nanomaterials might not be treated the same as insoluble ones.  

Nano-particle Study Generates More Heat Than Light

A new study published in the European Respiratory Journal is generating media attention, and some observers assert it may have far-reaching implications for the nano-tech industry. Is this warranted?

In this study, Song, et al., Exposure to nano-particles is related to pleural effusion, pulmonary fibrosis and granuloma, 34(3) Eur. Respir. J. 559-567 (2009), researchers at China's Capital University of Medical Sciences linked lung disease in seven Chinese workers, two of whom reportedly died, to nano-particle exposures in a print plant where a paste containing nano-particles was sprayed onto a polystyrene substrate, with subsequent heat-curing.

The study reported that seven young female workers (ages 18–47), exposed to nano-particles for 5–13 months, were admitted to the hospital, all with shortness of breath and pleural effusions. Polyacrylate, consisting of nano-particles, was confirmed in the workplace. Pathological examinations of the patients' lung tissue displayed non-specific pulmonary inflammation, pulmonary fibrosis, and foreign-body granulomas of pleura. By transmission electron microscopy, nano-particles were observed to have lodged in the cytoplasm and caryoplasm of pulmonary epithelial and mesothelial cells, but also were located in the chest fluid.

The authors expressed concern that long-term exposure to some nano-particles may be related to serious damage to human lungs.  But, putting the media reception aside, this study appears to do more to highlight the common sense need to follow good industrial hygiene practices than to provide compelling evidence of any unique health risks posed by engineered nano-particles. The plant sprayed a strong chemical paste and then heated plastic material in an enclosed space apparently lacking ventilation.  The room in which the women worked was small and unventilated for a significant part of their exposure period. Only on occasion, they wore mere "cotton gauze masks." 

From the study it appears that the workers had a complicated exposure history to a mix of chemicals; while there was a reported association of nano-particles with lung disease, it is unclear which, if any, of the chemical exposures might have contributed to the lung issues. Readers of MassTortDefense know that an association is not causation.  For example, formation of thermodegradation fume products are known to cause significant occupational disease, and paint spraying has been shown to be potentially harmful long before nano-sizing of chemicals was utilized. 

Moreover, sufficient exposure information necessary to even begin to think about a causal connection between exposure to nano-sized particles in the paste/dust and lung and heart disease in the workers was missing.  Clearly, there may be alternative explanations for what the study authors described finding in the patients.

As noted here before, NIOSH emphasizes the use of a variety of engineering control techniques, implementation of a risk management program in workplaces where exposure to nanomaterials exists, and use of good work practices to help to minimize worker exposures to nanomaterials.