Tag Archives: US Food and Drug Administration

DNA damage from engineered nanoparticles (zinc oxide, silver, silicon dioxide, cerium oxide and iron oxide)

Before launching into this research, there are a few provisos. This work was done in a laboratory, a highly specialized environment that does not mimic real-life conditions, and performed on animal cells (a hamster’s). As well, naturally occurring nanoparticles were not included (my Nov. 24, 2011 post has some information about naturally occurring nanomaterials including nanosilver which we have been ingesting for centuries).

That said, the studies from the Massachusetts Institute of Techology (MIT) and the Harvard School of Public Health (HSPH; last mentioned here in an April 2, 2014 post) are concerning (from an April 9, 2014 news item on Azonano).

A new study from MIT and the Harvard School of Public Health (HSPH) suggests that certain nanoparticles can also harm DNA. This research was led by Bevin Engelward, a professor of biological engineering at MIT, and associate professor Philip Demokritou, director of HSPH’s Center for Nanotechnology and Nanotoxicology.

The researchers found that zinc oxide nanoparticles, often used in sunscreen to block ultraviolet rays, significantly damage DNA. Nanoscale silver, which has been added to toys, toothpaste, clothing, and other products for its antimicrobial properties, also produces substantial DNA damage, they found.

The findings, published in a recent issue of the journal ACS Nano, relied on a high-speed screening technology to analyze DNA damage. This approach makes it possible to study nanoparticles’ potential hazards at a much faster rate and larger scale than previously possible.

More details about current testing requirements and the specific nanoparticles studied can be found in the April 8, 2014 MIT news release, which originated the news item,

The Food and Drug Administration does not require manufacturers to test nanoscale additives for a given material if the bulk material has already been shown to be safe. However, there is evidence that the nanoparticle form of some of these materials may be unsafe: Due to their immensely small size, these materials may exhibit different physical, chemical, and biological properties, and penetrate cells more easily.

“The problem is that if a nanoparticle is made out of something that’s deemed a safe material, it’s typically considered safe. There are people out there who are concerned, but it’s a tough battle because once these things go into production, it’s very hard to undo,” Engelward says.

The researchers focused on five types of engineered nanoparticles — silver, zinc oxide, iron oxide, cerium oxide, and silicon dioxide (also known as amorphous silica) — that are used industrially. Some of these nanomaterials can produce free radicals called reactive oxygen species, which can alter DNA. Once these particles get into the body, they may accumulate in tissues, causing more damage.

“It’s essential to monitor and evaluate the toxicity or the hazards that these materials may possess. There are so many variations of these materials, in different sizes and shapes, and they’re being incorporated into so many products,” says Christa Watson, a postdoc at HSPH and the paper’s lead author. “This toxicological screening platform gives us a standardized method to assess the engineered nanomaterials that are being developed and used at present.”

The researchers hope that this screening technology could also be used to help design safer forms of nanoparticles; they are already working with partners in industry to engineer safer UV-blocking nanoparticles. Demokritou’s lab recently showed that coating zinc oxide particles with a nanothin layer of amorphous silica can reduce the particles’ ability to damage DNA.

Given that Demokritou was part of a team that recently announced a new testing platform (Volumetric Centrifugation Method [VCM]) for nanoparticles as mentioned in my April 2, 2014 post, I was a little curious about the  platform for this project ( the CometChip) and, as always, curious about the results for all the tested engineered nanoparticles (Note: A link has been removed), from the news release,

Until now, most studies of nanoparticle toxicity have focused on cell survival after exposure. Very few have examined genotoxicity, or the ability to damage DNA — a phenomenon that may not necessarily kill a cell, but one that can lead to cancerous mutations if the damage is not repaired.

A common way to study DNA damage in cells is the so-called “comet assay,” named for the comet-shaped smear that damaged DNA forms during the test. The procedure is based on gel electrophoresis, a test in which an electric field is applied to DNA placed in a matrix, forcing the DNA to move across the gel. During electrophoresis, damaged DNA travels farther than undamaged DNA, producing a comet-tail shape.

Measuring how far the DNA can travel reveals how much DNA damage has occurred. This procedure is very sensitive, but also very tedious.

In 2010, Engelward and MIT professor Sangeeta Bhatia developed a much more rapid version of the comet assay, known as the CometChip. Using microfabrication technology, single cells can be trapped in tiny microwells within the matrix. This approach makes it possible to process as many as 1,000 samples in the time that it used to take to process just 30 samples — allowing researchers to test dozens of experimental conditions at a time, which can be analyzed using imaging software.

Wolfgang Kreyling, an epidemiologist at the German Research Center for Environmental Health who was not involved in the study, says this technology should help toxicologists catch up to the rapid rate of deployment of engineered nanoparticles (ENPs).

“High-throughput screening platforms are desperately needed,” Kreyling says. “The proposed approach will be not only an important tool for nanotoxicologists developing high-throughput screening strategies for the assessment of possible adverse health effects associated with ENPs, but also of great importance for material scientists working on the development of novel ENPs and safer-by-design approaches.”

Using the CometChip, the MIT and HSPH researchers tested the nanoparticles’ effects on two types of cells that are commonly used for toxicity studies: a type of human blood cells called lymphoblastoids, and an immortalized line of Chinese hamster ovary cells.

Zinc oxide and silver produced the greatest DNA damage in both cell lines. At a concentration of 10 micrograms per milliliter — a dose not high enough to kill all of the cells — these generated a large number of single-stranded DNA breaks.

Silicon dioxide, which is commonly added during food and drug production, generated very low levels of DNA damage. Iron oxide and cerium oxide also showed low genotoxicity.

Happily the researchers are taking a pragmatic approach to the results (from the news release),

More studies are needed to determine how much exposure to metal oxide nanoparticles could be unsafe for humans, the researchers say.

“The biggest challenge we have as people concerned with exposure biology is deciding when is something dangerous and when is it not, based on the dose level. At low levels, probably these things are fine,” Engelward says. “The question is: At what level does it become problematic, and how long will it take for us to notice?”

One of the areas of greatest concern is occupational exposure to nanoparticles, the researchers say. Children and fetuses are also potentially at greater risk because their cells divide more often, making them more vulnerable to DNA damage.

The most common routes that engineered nanoparticles follow into the body are through the skin, lungs, and stomach, so the researchers are now investigating nanoparticle genotoxicity on those cell types. They are also studying the effects of other engineered nanoparticles, including metal oxides used in printer and photocopier toner, which can become airborne and enter the lungs.

Kudos to the writer for the clarity and care shown here (I think it’s Anne Trafton but MIT is not including bylines as it did previously, so I’m uncertain).

Here’s a link to and a citation for the research paper,

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology by Christa Watson, Jing Ge, Joel Cohen, Georgios Pyrgiotakis, Bevin P. Engelward, and Philip Demokritou. ACS Nano, 2014, 8 (3), pp 2118–2133 DOI: 10.1021/nn404871p Publication Date (Web): March 11, 2014
Copyright © 2014 American Chemical Society

This article is behind a paywall.

Food and nanotechnology (as per Popular Mechanics) and zinc oxide nanoparticles in soil (as per North Dakota State University)

I wouldn’t expect to find an article about food in a magazine titled Popular Mechanics but there it is, a Feb. 19,2014 article by Christina Ortiz (Note: A link has been removed),

For a little more than a decade, the food industry has been using nanotechnology to change the way we grow and maintain our food. The grocery chain Albertsons currently has a list of nanotech-touched foods in its home brand, ranging from cookies to cheese blends.

Nanotechnology use in food has real advantages: The technology gives producers the power to control how food looks, tastes, and even how long it lasts.

Looks Good and Good for You?

The most commonly used nanoparticle in foods is titanium dioxide. It’s used to make foods such as yogurt and coconut flakes look as white as possible, provide opacity to other food colorings, and prevent ingredients from caking up. Nanotech isn’t just about aesthetics, however. The biggest potential use for this method involves improving the nutritional value of foods.

Nano additives can enhance or prevent the absorption of certain nutrients. In an email interview with Popular Mechanics, Jonathan Brown, a research fellow at the University of Minnesota, says this method could be used to make mayonnaise less fattening by replacing fat molecules with water droplets.

I did check out US grocer, Albertson’s list of ‘nanofoods’, which they provide and discovered that it’s an undated listing on the Project of Emerging Nanotechnologies’ Consumer Products Inventory (CPI). The inventory has been revived recently after lying moribund for a few years (my Oct. 28, 2013 posting describes the fall and rise) and I believe that this 2013 CPI incarnation includes some oversight and analysis of the claims made, which the earlier version did not include. Given that the Albertson’s list is undated it’s difficult to assess the accuracy of the claims regarding the foodstuffs.

If you haven’t read about nanotechnology and food before, the Ortiz article provides a relatively even-handed primer although it does end on a cautionary note. In any event, it was interesting to get a bit of information about the process of ‘nanofood’ regulation in the US and other jurisdictions (from the Ortiz article),

Aside from requiring manufacturers to provide proof that nanotechnology foods are safe, the FDA has yet to implement specific testing of its own. But many countries are researching ways to balance innovation and regulation in this market. In 2012 the European Food Safety Authority (EFSA) released an annual risk assessment report outlining how the European Union is addressing the issue of nanotech in food. In Canada the Food Directorate “is taking a case-by-case approach to the safety assessment of food products containing or using nanomaterials.”

I featured the FDA’s efforts regarding regulation and ‘nanofood’ in an April 23, 2012 posting,

It looks to me like this [FDA's draft guidance for 'nanofoods'] is an attempt to develop a relationship where the industry players in the food industry to police their nanotechnology initiatives with the onus being on industry to communicate with the regulators in a continuous process, if not at the research stage certainly at the production stage.

At least one of the primary issues with any emerging technology revolves around the question of risk. Do we stop all manufacturing and development of nanotechnology-enabled food products until we’ve done the research? That question assumes that taking any risks is not worth the currently perceived benefits. The corresponding question, do we move forward and hope for the best? does get expressed perhaps not quite so baldly; I have seen material which suggests that research into risks needlessly hampers progress.

After reading on this topic for five or so years, my sense is that most people are prepared to combine the two approaches, i.e., move forward while researching possible risks. The actual conflicts seem to centre around these questions, how quickly do we move forward; how much research do we need; and what is an acceptable level of risk?

On the topic of researching the impact that nanoparticles might have on plants (food or otherwise), a January 24, 2013 North Dakota State University (NDSU) news release highlights a student researcher’s work on soil, plants, and zinc oxide nanoparticles,

NDSU senior Hannah Passolt is working on a project that is venturing into a very young field of research. The study about how crops’ roots absorb a microscopic nutrient might be described as being ahead of the cutting-edge.

In a laboratory of NDSU’s Wet Ecosystem Research Group, in collaboration with plant sciences, Passolt is exploring how two varieties of wheat take up extremely tiny pieces of zinc, called nanoparticles, from the soil.

As a point of reference, the particles Passolt is examining are measured at below 30 nanometers. A nanometer is 1 billionth of a meter.

“It’s the mystery of nanoparticles that is fascinating to me,” explained the zoology major from Fargo. “The behavior of nanoparticles in the environment is largely unknown as it is a very new, exciting science. This type of project has never been done before.”

In Passolt’s research project, plants supplied by NDSU wheat breeders are grown in a hydroponic solution, with different amounts of zinc oxide nanoparticles introduced into the solution.

Compared to naturally occurring zinc, engineered zinc nanoparticles can have very different properties. They can be highly reactive, meaning they can injure cells and tissues, and may cause genetic damage. The plants are carefully observed for any changes in growth rate and appearance. When the plants are harvested, researchers will analyze them for actual zinc content.

“Zinc is essential for a plant’s development. However, in excess, it can be harmful,” Passolt said. “In one of my experiments, we are using low and high levels of zinc, and the high concentrations are showing detrimental effects. However, we will have to analyze the plants for zinc concentrations to see if there have been any effects from the zinc nanoparticles.”

Passolt has conducted undergraduate research with the Wet Ecosystem Research Group for the past two years. She said working side-by-side with Donna Jacob, research assistant professor of biological sciences; Marinus Otte; professor of biological sciences; and Mohamed Mergoum, professor of plant sciences, has proven to be challenging, invigorating and rewarding.

“I’ve gained an incredible skill set – my research experience has built upon itself. I’ve gotten to the point where I have a pretty big role in an important study. To me, that is invaluable,” Passolt said. “To put effort into something that goes for the greater good of science is a very important lesson to learn.”

According to Jacob, Passolt volunteered two years ago, and she has since become an important member of the group. She has assisted graduate students and worked on her own small project, the results of which she presented at regional and international scientific conferences. “We offered her this large, complex experiment, and she’s really taken charge,” Jacob said, noting Passolt assisted with the project’s design, handled care of the plants and applied the treatments. When the project is completed, Passolt will publish a peer-reviewed scientific article.

“There is nothing like working on your own experiment to fully understand science,” Jacob said. “Since coming to NDSU in 2006, the Wet Ecosystem Research Group has worked with more than 50 undergraduates, possible only because of significant support from the North Dakota IDeA Networks of Biomedical Research Excellence program, known as INBRE, of the NIH National Center for Research Resources.”

Jacob said seven undergraduate students from the lab have worked on their own research projects and presented their work at conferences. Two articles, so far, have been published by undergraduate co-authors. “I believe the students gain valuable experience and an understanding of what scientists really do during fieldwork and in the laboratory,” Jacob said. “They see it is vastly different from book learning, and that scientists use creativity and ingenuity daily. I hope they come away from their experience with some excitement about research, in addition to a better resume.”

Passolt anticipates the results of her work could be used in a broader view of our ecosystem. She notes zinc nanoparticles are an often-used ingredient in such products as lotions, sunscreens and certain drug delivery systems. “Zinc nanoparticles are being introduced into the environment,” she said. “It gets to plants at some point, so we want to see if zinc nanoparticles have a positive or negative effect, or no effect at all.”

Researching nanoparticles the effects they might have on the environment and on health is a complex process as there are many types of nanoparticles some of which have been engineered and some of which occur naturally, silver nanoparticles being a prime example of both engineered and naturally occurring nanoparticles. (As well, the risks may lie more with interactions between nanomaterials.) For an example of research, which seems similar to the NDSU effort, there’s this open access research article,

Low Concentrations of Silver Nanoparticles in Biosolids Cause Adverse Ecosystem Responses under Realistic Field Scenario by Benjamin P. Colman, Christina L. Arnaout, Sarah Anciaux, Claudia K. Gunsch, Michael F. Hochella Jr, Bojeong Kim, Gregory V. Lowry,  Bonnie M. McGill, Brian C. Reinsch, Curtis J. Richardson, Jason M. Unrine, Justin P. Wright, Liyan Yin, and Emily S. Bernhardt. PLoS ONE 2013; 8 (2): e57189 DOI: 10.1371/journal.pone.0057189

One last comment, the Wet Ecosystem Research Group (WERG) mentioned in the news release about Passolt has an interesting history (from the homepage; Note: Links have been removed),

Marinus Otte and Donna Jacob brought WERG to the Department of Biological Sciences in the Fall of 2006.  Prior to that, the research group had been going strong at University College Dublin, Ireland, since 1992.

The aims for the research group are to train graduate and undergraduate students in scientific research, particularly wetlands, plants, biogeochemistry, watershed ecology and metals in the environment.  WERG research  covers a wide range of scales, from microscopic (e.g. biogeochemical processes in the rhizosphere of plants) to landscape (e.g. chemical and ecological connectivity between prairie potholes across North Dakota).  Regardless of the scale, the central theme is biogeochemistry and the interactions between multiple elements in wet environments.

The group works to collaborate with a variety of researchers, including soil scientists, geologists, environmental engineers, microbiologists, as well as with groups underpinning management of natural resources, such the Minnesota Department of Natural Resources, the Department of Natural Resources of Red Lake Indian Reservation, and the North Dakota Department of Health, Division of Water Quality.

Currently, WERG has several projects, mostly in North Dakota and Minnesota.  Otte and Jacob are also Co-directors of the North Dakota INBRE Metal Analysis Core, providing laboratory facilities and mentoring for researchers in undergraduate colleges throughout the state. Otte and Jacob are also members of the Upper Midwest Aerospace Consortium.

Dengue fever and NanoViricides, Inc.

Since 1970, dengue has grown to be a major health problem according to the World Health Organization Fact Sheet no. 117 (November 2012) and it’s one NanoViricides, Inc. hopes to tackle with its current European Medicines Agency (EMA) drug application. From the July 2, 2013 news item on Azonano,

NanoViricides, Inc. (the “Company”) announced today that it has submitted its letter of intent to file an Orphan Drug Application with the European Medicines Agency (EMA) for DengueCide™, its drug candidate for the treatment of dengue and dengue hemorrhagic fever.

EMA requires a notification of intent to file at least 60 days prior to the actual filing, unlike the US FDA. The actual application will need to be translated into 27 different languages prior to submission.

… The Company has recently filed an Orphan Drug Designation application for DengueCide to the US FDA.

The July 1, 2013 NanoViricides news release, which originated the news item, goes on to explain (a direct link to the news release is not possible but you can find it on the company’s home page),

Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyper-endemicity (the co-circulation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 2013, this mosquito-borne disease is one of the most important tropical infectious diseases globally, with an estimated 400 million cases of dengue fever, over one million cases of dengue hemorrhagic fever, and 50,000-100,000 deaths annually. Dengue virus occurs in four primary serotypes. Although the disease is endemic in many tropical parts of the world, it is considered an orphan disease in the USA and Europe. (From Clinical Microbiology Reviews).

The news release also describes the proposed DengueCide treatment’s effectiveness in animal trials,

DengueCide is a nanoviricide® that has shown very high effectiveness in an animal model of dengue virus infection. These animal studies were conducted in the laboratory of Dr. Eva Harris, Professor of Public Health and Infectious Diseases at the University of California, Berkeley. Professor Harris has developed a mouse model simulating antibody-dependent-enhancement (ADE) of dengue infection using a special laboratory mouse strain called AG129. ADE in humans is thought to to lead to dengue hemorrhagic fever, and is associated with a high fatality rate. In this model, infection with a dengue virus, when the mice are left untreated, is 100% fatal. In contrast, in the same study, animals treated with NanoViricides’ DengueCide achieved an unprecedented 50% survival rate.

There is currently neither an effective drug treatment nor a vaccine for dengue virus infection. Tremendous efforts have been made for dengue vaccine development but, to date, no vaccine candidate has succeeded in clinical trials towards approval.

In an attempt to give their DengueCide application more heft, the news release provides a description of the company’s work with anti-influenza drugs,

NanoViricides is developing broad-spectrum anti-influenza drugs as part of its rich drug pipeline. The Company believes that its FluCide™ drug candidates will be effective against most if not all influenza viruses, including the H7N9 bird flu, H3N2 or H1N1 epidemic viruses, H5N1 bird flu, seasonal influenzas, as well as novel influenza viruses. This is because FluCide is based on the Company’s biomimetic technology, mimicking the natural sialic acid receptors for the influenza virus on the surface of a nanoviricide® polymeric micelle. It is important to note that all influenza viruses bind to the sialic acid receptors, even if they rapidly mutate. The FluCide drug candidates have already shown strong effectiveness against H1N1 and H3N2 influenza viruses in highly lethal animal models. The injectable FluCide drug candidates have shown 1,000X greater viral load reduction as compared to oseltamivir (Tamiflu®), the current standard of care, in a highly lethal influenza infection animal model. The Company believes that these animal model results should translate readily into humans.

NanoViricides has also developed an oral drug candidate against influenza. This oral version is also dramatically more effective than TamiFlu in the animals given a lethal influenza virus infection. This oral FluCide may be the very first nanomedicine that is effective when taken by mouth.

I hope they are successful with this new dengue drug. Oddly, the news release seemed to understate the scope of the problem. Here’s more from the WHO (World Health Organization) fact sheet no. 117,

The incidence of dengue has grown dramatically around the world in recent decades. Over 2.5 billion people – over 40% of the world’s population – are now at risk from dengue. WHO currently estimates there may be 50–100 million dengue infections worldwide every year.

Before 1970, only nine countries had experienced severe dengue epidemics. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. The American, South-east Asia and the Western Pacific regions are the most seriously affected.

Cases across the Americas, South-east Asia and Western Pacific have exceeded 1.2 million cases in 2008 and over 2.3 million in 2010 (based on official data submitted by Member States). Recently the number of reported cases has continued to increase. In 2010, 1.6 million cases of dengue were reported in the Americas alone, of which 49 000 cases were severe dengue.

Not only is the number of cases increasing as the disease spreads to new areas, but explosive outbreaks are occurring. The threat of a possible outbreak of dengue fever now exists in Europe and local transmission of dengue was reported for the first time in France and Croatia in 2010 and imported cases were detected in three other European countries. A recent (2012) outbreak of dengue on Madeira islands of Portugal has resulted in over 1800 cases and imported cases were detected in five other countries in Europe apart from mainland Portugal.

An estimated 500 000 people with severe dengue require hospitalization each year, a large proportion of whom are children. About 2.5% of those affected die.

Human Bionic Project; amputations, prosthetics. and disabilities

Sydney Brownstone’s June 26, 2013 article about The Human Bionic Project  for Fast Company touches on human tragedy and the ways in which we attempt to cope by focusing on researcher David Sengeh’s work (Note: Links have been removed),

In the Iraq and Afghanistan wars alone, nearly 1,600 American soldiers have woken up without a limb. Fifteen survivors of the Boston marathon bombings are new amputees. And in Sierra Leone, where MIT graduate student David Sengeh is from, brutal tactics during the country’s 11-year civil war resulted in somewhere between 4,000 and 10,000 amputations in a country of less than 6 million people.

Many amputees go through the costly, lengthy process of transitioning to prosthetics, but it’s difficult even for prosthetic research specialists to gather information about the replacement parts outside their narrow fields. That’s part of the reason why, in December of last year, Sengeh and a research team began developing an interactive Inspector Gadget–a repository of all the FDA-approved [US Food and Drug Administration] replacement parts they could find.

So far, the Human Bionic Project has between 40 and 50 points of reference on its corporeal map–everything from artificial hearts to bionic jaws. In addition to photos and descriptions, the team will soon be looking to source videos of prosthetics in action from the public. Sengeh also hopes to integrate a timeline, tracking bionic parts throughout history, from the bionic toes of Ancient Egypt to the 3-D printed fingers of modern times.

“In [Haitian and Sierra Leonian] Creole, the word for disabled, like an amputee, is ‘scrap,’” Sengeh said. “I wanted to change that, because I know that we can get full functionality and become able-bodied.”

Do read Brownstone’s article as I haven’t, by any means, excerpted all the interesting bits.

There’s also more at The Human Bionic Project. Here’s a description (or manifesto) from the home page,

The Human Bionic Project begs for the fundamental redefinition of disability, illness, and disease as we have known it throughout history. It dares us to imagine the seamless interaction between the human being and machines. This interactive learning platform enables the user to visualize and learn about the comprehensive advances in human repair and enhancement that can be achieved with current technology. We can also wonder about what the human being will look like by the 22nd Century (year 2100) based on cutting edge advances in science and technology — more specifically in the fields of biomechanics, and electronics.

The Human Bionic Project serves as a call to action for technologists all around the world to think about the design of bionics in a fundamentally new way; how can we engineer all bionic elements for the human body using a similar protocol and architecture? Could we have the behaviour of the bionic knee be in sync with that of the bionic ankle of an above-knee amputee? How can we design a bionic eye that sees beyond what the biological eye can observe and use that information to help humans in critical situations? We have to imagine bionics not as singular units developed to replace or augment human parts but rather as part of a human-bionic system aimed at redefining what it means to be human.

Some of the ideas presented are already products used today, while others are prototypes explored by various research laboratories and inquisitive humans around the world. The works presented here are not ours and are publicly available. We have credited all the authors who are leading these extraordinary research initiatives.

You can find more about prosthetics, etc. on the ‘Inspector Gadget‘ page (it features an outline of a human body highlighted with red dots (click on a red dot to get details about prosthetics and other forms of augmentation). I don’t find this to be an especially friendly or intuitive interface. I think this is an MIT (Massachusetts Institute of Technology) student project and I find MIT tends to favour minimalism on its institutional and student websites. Still, there’s some fascinating information if you care to persist.

Here are more details about the folks and the funding supporting The Human Bionic Project (from the bottom of the home  page),

A project by David Moinina Sengeh. Collaborator: Reza Naeeni. Web development: Yannik Messerli. Undergraduate research assistant: Nicholas Fine. Funded by The Other Festival at MIT Media Lab (2013). Follow us on twitter: @humanbionicproj. …

I last mentioned human enhancement/augmentation in my June 17, 2013 commentary on You Are Very Star, a transmedia theatre experience taking place in Vancouver until June 29, 2013. I have written many times on the topic of human enhancement including a May 2, 2013 posting about a bionic ear; a Feb. 15, 2013 posting about a bionic eye; and a Jan. 30, 2013 posting about a BBC documentary on building a bionic man, amongst others.

Organ chips for DARPA (Defense Advanced Research Projects Agency)

The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project.

I note that Kevin Kit Parker was mentioned in an earlier posting today (July 26, 2012) titled, Medusa, jellyfish, and tissue engineering, and Donald Ingber in my Dec.1e, 2011 posting about Shrilk and insect skeletons.

As for the Wyss Institute, here’s a description from the news release,

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

I hadn’t thought of an organ-on-a-chip as particularly bioinspired so I’ll have to think about that one for a while.

Do the US FDA guidance documents for nanotechnology in food and in cosmetics matter?

The US Food and Drug Administration (FDA) has issued two documents that provide guidance to manufactures of food products and cosmetics according to the April 20, 2012 news item on Nanowerk,

Two draft guidance documents that address the use of nanotechnology by the food and cosmetics industries were issued today by the U.S. Food and Drug Administration.

Nanotechnology is an evolving technology that allows scientists to create, explore, and manipulate materials on a scale measured in nanometers – particles so small that they can not be seen with a regular microscope. The technology has a broad range of potential applications, such as the packaging of food or altering the look and feel of cosmetics. [emphasis mine]

They might also have indicated food additives and other ingredients are covered in the guidance. I mention this because I noticed that some of the news coverage does not make that point and people are likely to believe that it covers only food packaging and not ingredients.

You can check out the guidance documents (both the one for foods and the one for cosmetics) for yourself,

Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives

Draft Guidance for Industry: Safety of Nanomaterials in Cosmetic Products

This US FDA April 20, 2012 press announcement offers some details,

The food draft guidance describes the factors manufacturers should consider when determining whether changes in manufacturing processes, including those involving nanotechnology, create a significant change that may:

  • affect the identity of the food substance;
  • affect the safety of the use of the food substance;
  • affect the regulatory status of the use of the food substance; or
  • warrant a regulatory submission to FDA.

The cosmetic product draft guidance discusses the FDA’s current thinking on the safety assessment of nanomaterials when used in cosmetic products. Key points include:

  • The legal requirements for cosmetics manufactured using nanomaterials are the same as those for any other cosmetics. While cosmetics are not subject to premarket approval, companies and individuals who market cosmetics are legally responsible for the safety of their products and they must be properly labeled.
  • To conduct safety assessments for cosmetic products containing nanomaterials, standard safety tests may need to be modified or new methods developed.

Both guidances encourage manufacturers to consult with the agency before taking their products to market. Such consultation can help FDA experts address questions related to the safety or other attributes of nanotechnology products, or answer questions about their regulatory status.

Strong science is critical to FDA’s ongoing review of the products it regulates.  FDA is investing in an FDA-wide nanotechnology regulatory science program to further enhance FDA’s scientific capabilities, including developing necessary data and tools to identify properties of nanomaterials and assess the impact they may have on products.

“Understanding nanotechnology remains a top FDA priority. FDA is strengthening the scientific tools and methods for evaluating food products, cosmetics, drugs and medical devices,” said FDA Commissioner Margaret A. Hamburg, M.D. “We are taking a prudent scientific approach to assess each product on its own merits and to not make broad, general assumptions about the safety of nanotechnology products.”

The FDA’s current thinking concerning nanomaterials for food and cosmetics uses, explained in the two guidance documents, is not intended to provide guidance to manufacturers about the use of nanomaterials in other products, such as drugs or medical devices, regulated by the FDA.

It’s still possible to comment on the guidelines as they are at a ‘draft’ stage, from the FDA’s April 20, 2012 press announcement,

In order to ensure that FDA considers comments on these draft guidances in developing the final guidances, electronic or written comments should be submitted within 90 days of the publication of the notices of availability in the Federal Register. The FDA will carefully consider all relevant, substantive comments during the development of the final guidance documents.

Electronic comments should be submitted to http//www.regulations.gov. Written comments should be submitted to the Division of Dockets Management, (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.

It looks to me like this is an attempt to develop a relationship where the industry players in the food industry to police their nanotechnology initiatives with the onus being on industry to communicate with the regulators in a continuous process, if not at the research stage certainly at the production stage. That same request is being made to the cosmetics industry, from the draft guidance document for cosmetic products,

If you wish to use a nanomaterial in a cosmetic product, either a new material or an altered version of an already marketed ingredient, FDA encourages you to meet with us to discuss the test methods and data needed to substantiate the product’s safety, including chronic toxicity and other long-term toxicity data as appropriate.  Individuals outside the Federal Government may request a private meeting with a representative of FDA to discuss a matter, and FDA will make reasonable efforts to accommodate such requests (21 CFR 10.65(c)).  We encourage you to take advantage of this provision and contact us to discuss any aspect of the safety assessment of cosmetic ingredients or finished products.

You can read some additional commentary about both draft guidelines in the April 22, 2012 posting on redOrbit, the April 20, 2012 news item by Torie Bosch for Slate magazine, and  the April 20, 2012 Reuters article by Anna Yukhananov in the Chicago Tribune.

One odd thing I noticed in some articles and commentaries (e.g. Reuters article by Anna Yukhananov) is a reference to the European Union rules with regard to cosmetics products. The observers seemed to be under the impression that cosmetics companies with European production facilities and/or headquarters would operate under the same rules in North America. From the Yukhananov article,

The FDA does not require cosmetic companies to submit safety data before selling their products, and the guidance is unlikely to have a big impact on large cosmetic firms like Avon Products Inc, which already comply with European rules.

Why would Avon extend its compliance with European Union (EU) rules to its US operations? Companies routinely operate under different rules in different countries and regions.

Getting back to the question I asked in the headline, do these guidance documents matter? Yes, as stated earlier, I think this is an attempt to develop a relationship with open communication and where industry is being respected enough to manage/police itself. One hopes that this is not misplaced trust.

Nanodiagnostics: a roundtable at Kavli and new report from Cientifica

The Kavli Foundation, based in California, held a roundtable discussion on ‘Fighting Cancer with Nanotechnology‘ which focused largely on diagnostics and drug delivery. According to a March 14, 2012 news item on Nanowerk, the four participants were:

  • Anna Barker – Former Deputy Director of the National Cancer Institute (NCI) and current Director of Arizona State University’s Transformative Healthcare Networks;
  • Mark E. Davis – Professor of Chemical Engineering at the California Institute of Technology (Caltech), and a member of the Experimental Therapeutics Program of the Comprehensive Cancer Center at the City of Hope;
  • James Heath – Professor of Chemistry at Caltech and a founding Board member of Caltech’s Kavli Nanoscience Institute;
  • Michael Phelps – Norton Simon Professor, and Chair of Molecular and Medical Pharmacology at the University of California Los Angeles.

The researchers discussed how nanotechnology holds the promise of revolutionizing the way medicine wages war against cancer, from providing new ways to combine drugs to delivering gene-silencing therapeutics for cancer cells. [emphasis mine]

Yet again, war has been used as a metaphor for healing. I particularly appreciate the way ‘revolution’, which resonates with US audiences in a very particular way, has been introduced.

The discussion features diagnostics,

JAMES HEATH: That is certainly an important application. A typical diagnostic test measures only a single protein. But the nature of cancer—even a single cancer type—is that it can vary significantly from patient to patient. The implication is that there is probably not a single protein biomarker that can distinguish between such patient variations. Even to confidently address a single diagnostic question may take measuring several protein biomarkers. Discovering the right biomarkers is extremely challenging—you might have 300 candidate biomarkers from which you want to choose just six, but you will likely have to test all 300 on a very large patient pool to determine the best six. That’s tough to do with existing technologies because each protein measurement requires a large sample of blood or tumor tissue, and each measurement is time-consuming, labor intensive and expensive. With some of the emerging nanotechnologies, a large panel of candidate protein biomarkers can be rapidly measured from just a pinprick of blood, or a tissue sample as small as a single cell. This allows one to accelerate the development of conventional diagnostic tests, but it also opens up the possibilities for fundamentally new diagnostic approaches. These are opportunities that nanotech is bringing into play that simply weren’t there before.

Here’s one of my favourite comments,

MICHAEL PHELPS: Yes. All of us developing therapeutics want to have a transparent patient—to see where the drug goes throughout all tissues of the body, whether it hits the disease target in a sufficient dose to induce the desired therapeutic effect on the target, and where else the drug goes in the body regarding side effects. [emphasis mine] PET [positron emission tomography 'scan'] can reveal all this. For this reason almost all drug companies now use PET in their discovery and development processes.

I suspect Phelps was a bit over enthused and spoke without thinking. I’m sure most doctors and researchers would agree that what they want is to heal without harm and not transparent patients. That’s why they’re so excited about nanotechnology and therapeutics, they’re trying to eliminate or, at least, lessen harm in the healing process. It would be nice though if they get past the ‘war’ metaphors and dreams of transparent patients.

I found the comments about the US FDA (Food and Drug Administration), pharmaceutical companies and biotech startups quite interesting,

ANNA BARKER: These challenges are mostly related to perception and having the tools to demonstrate that the agent does what you say it does. It’s more difficult for nanotherapeutics than for other drugs because they employ a new set of technologies that the FDA is more guarded about approving. The FDA is responsible for the health of the American public, so they are very careful about putting anything new into the population. So the challenges have to do with showing you can deliver what you said you were going to deliver to the target, and that the toxicity and distribution of the agent in the body is what you predicted. You have to have different measures than what is included in the classic toxicology testing packages we use for potential drugs.

MARK DAVIS: There’s so much cool science that people want to do, but you’re limited in what you can do in patients for a number of reasons. One is financial. This area is not being pushed forward by big Pharma, but by biotech companies, and they have limited resources. Secondly, the FDA is still learning about these innovations, they can limit what you are allowed to do in a clinical trial. For example, when we did the first clinical trial with a nanoparticle that had a targeting agent enabling it to latch onto a specific receptor on cancer cells and a gene silencing payload, we realized it would be important to know if patients have this receptor and the gene target of the payload to begin with. Prebiopsies from patients before testing the nanotherapeutic on them to see if the tumor cells had this receptor and gene target in abundance would have been helpful. However, in this first-in-man trial, the FDA did not allow required biopsies, and they were performed on a volunteer-basis only.

It is a fascinating discussion as it provides insight into the field of nanotherapeutics and into the some of the researchers.

On the topic of nanodiagnostics but this time focusing on the business end of things, a new report has been released by Cientifica. From the March 13, 2012 press release,

Nanodiagnostics will be a $50-billion market by 2021; Cientifica’s “Nanotechnology for Medical Diagnostics” looks at emerging nanoscale technologies

Following on from Cientifica’s Nanotechnology for Drug Delivery report series, “Nanotechnology for Medical Diagnostics,” a 237-page report, takes a comprehensive look at current and emerging nanoscale technologies used for medical diagnostics.

Areas examined include quantum dots, gold nanoparticles, exosomes, nanoporous silica, nanowires, micro- and nanocantilever arrays, carbon nanotubes, ion channel switch nanobiosensors, and many more.

Cientifica estimates medical imaging is the sector showing the highest growth and impact of nanomaterials. Already a $1.7-billion market, with gold nanoparticle applications accounting for $959 million, imaging will continue to be the largest nanodiagnostics sector, with gold nanoparticles, quantum dots and nanobiosensors all easily exceeding $10 billion.

“Getting onboard with the right technology at the right time is crucial,” said Harper [Tim Harper, Cientifica's Chief Executive Officer]. “The use of exosomes in diagnosis, for instance, a relatively new technique and a tiny market, is set to reach close to half a billion dollars by 2021.”

You can find out more and/or purchase the report here.

I have written about Cientifica’s  Nanotechnology for Drug Delivery (NDD) white paper here and have published an interview with Tim Harper about global nanotechnology funding and economic impacts here.

First lawsuit on risks of nanotechnology?

I got this Dec. 21, 2011 news release this morning,
 

Consumer Safety Groups File First Lawsuit on Risks of Nanotechnology

San Francisco, CA – Concerned by the growing body of scientific reports cautioning against the unregulated use of nanotechnology in consumer products, a coalition of nonprofit consumer safety and environmental groups sued the Food and Drug Administration (FDA) today.  The case is the first lawsuit over the health and environmental risks of nanotechnology and nanomaterials.

Nanotechnology is a powerful platform technology for taking apart and reconstructing nature at the atomic and molecular level.  Just as the size and chemical characteristics of manufactured nanomaterials give them unique properties, those same properties – tiny size, vastly increased surface area to volume ratio, and high reactivity – can also create unique and unpredictable health and environmental risks.

The lawsuit demands FDA respond to a petition the public interest organizations filed with the agency in 2006, nearly six years ago.  The coalition is led by the International Center for Technology Assessment (CTA), on behalf of fellow plaintiffs Friends of the Earth, Food and Water Watch, the Center for Environmental Health, the ETC Group, and the Institute for Agricultural and Trade Policy.

“Nano means more than tiny; it means materials that have the capacity to be fundamentally different.  Yet more and more novel nanomaterials are being sold infused into new consumer products every day, while FDA sits idly by,” said George Kimbrell, ICTA Attorney.  “The agency’s unlawful delay unnecessarily places consumers and the environment at risk.”

The eighty-page petition documents the scientific evidence of nanomaterial risks stemming from their unpredictable toxicity and seemingly unlimited mobility.  The 2006 petition [http://www.icta.org/doc/Nano%20FDA%20petition%20final.pdf] requested FDA take several regulatory actions, including requiring nano-specific product labeling and health and safety testing, and undertaking an analysis of the environmental and health impacts of nanomaterials in products approved by the agency.

Nanomaterials in sunscreens, one of the largest sectors of the nano-consumer product market, were also a focus of the action.  The petitioners called on the agency to regulate nano-sunscreens to account for their novel ingredients rather than assume their safety, and to pull such sunscreens from the market until and unless the agency approves them as new drug products.

“Year after year goes by but we have yet to see the FDA do the bare minimum and require nanosunscreens to be labeled as such. This is a basic consumer right,” said Ian Illuminato of Friends of the Earth.  “We’re well past the 1800s — nobody likes or should be forced to use mystery chemicals anymore.”

Since 2006, numerous studies and reports, including agency publications by the Environmental Protection Agency, the Office of the Inspector General, and the U.S. Government Accountability Office, acknowledge significant data gaps concerning nanomaterials’ potential effects on human health and the environment.  Most troubling are studies using mice that show that nano-titanium dioxide when inhaled and when eaten can cause changes in DNA that affect the brain function and may cause tumors and developmental problems in offspring.  One study found titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain.

“It is unacceptable that the FDA continues to allow unregulated and unlabeled nanomaterials to be used in products consumers use every day,” said Wenonah Hauter, executive director of Food & Water Watch. “It is past time for this agency to live up to its mission and protect public health by assessing the health and environmental risks of nanomaterials, and to require labeling so that consumers know where these new materials are being used.”

“The scientific consensus is that nanomaterials require specific testing to account for their novel capacities and potential risks.  The FDA must do such testing as part of a pre-market safety assessment in a broader regulatory initiative to protect public health,” said Steve Suppan of the Institute for Agriculture and Trade Policy.

For more, see generally (http://www.icta.org/about/).

Despite the headline ICTA gave this news release, I found a 2008 news release for another nanotechnology law suit where they were suing the US Environmental Protection Agency,  GROUPS DEMAND EPA STOP SALE OF 200+ POTENTIALLY DANGEROUS NANO-SILVER PRODUCTS; Nanotech Watchdog Launches First-Ever Legal Challenge To EPA Over Unregulated Nanotech Pesticide Pollution.

If I understand this rightly, the ICTA along with its coalition partners is suing the FDA for not responding to its petition, which would have made for a much less compelling headline. I didn’t have much luck accessing the 2006 petition (clicking on the link brought up an error page) but will try again later.

I notice that sunscreens with with nanoscale titanium dioxide are used as an example of the use of dangerous nanomaterials in consumer products. It seems the general consensus is that nanoscale titanium dioxide and/or zinc oxide used in nanosunscreens are relatively safe. You can read more about this on the Cancer Council of Australia or the Environmental Working Group (EWG) websites. From the EWG,

EWG reviewed the scientific literature on hazards and efficacy (UVB and UVA protection) for all active ingredients approved in the U.S. Though no ingredient is without hazard or perfectly effective, on balance our ratings tend to favor mineral sunscreens because of their low capacity to penetrate the skin and the superior UVA protection they offer.

I really wish they would stop using the nanosunscreens as their ‘go to’ concern as I think it damages these groups’ credibility.

Still, the FDA should respond to a petition and six years seems like a long time to wait.

US National Nanotechnology Initiative reports on last year’s recommendations

Richard M. Jones at the American Institute of Physics (AIP) reports in a Dec. 9, 2011 article in the AIP Bulletin no. 145,

Members of the President’s Council of Advisors on Science and Technology [PCAST] were briefed last month on the implementation of the council’s recommendations regarding the National Nanotechnology Initiative (NNI).  Now in its tenth year, federal agencies participating in the NNI expend about $2 billion per year, having spent a cumulative $14 billion on nanotechnology R&D since its inception.

Jones summarized the presentations (here’s a sampling),

Sally Tinkle, Deputy Director of the National Nanotechnology Coordination Office was the first of four speakers in this sixty-minute briefing. … As examples, she described an increase in the number of public-private partnerships (citing examples from the NIH and NIST), outreach to states (including a full-time employee dedicated to this effort), interactions with officials from the European Union,  better information dissemination programs, and research on health, environmental, safety, ethical, and legal matters.  …

Carlos Pena, Director of Emerging Technology at the Office of Science and Health Coordination of the Food and Drug Administration was the second speaker. He described FDA’s efforts to carefully protect human health while fostering the development of nanotechnology, using science-based decision making. Among those steps it has taken is increasing training of its staff and improved coordination and cooperation with other agencies. …

Other topics covered in a concluding question-and-answer period included monthly inter-agency briefings, meetings with the European Union, products awaiting FDA approval, federal agency funding collaborations, the desirability of a multi-agency roadmap to support further development of nanotechnology, the engagement of nongovernmental stakeholders, and computational support.

You can access the webcast, briefing materials, minutes, etc. from the Nov. 2, 2011 meeting here.

You can view the webcast here.

What I find most interesting is that this particular US government administration is making a big effort at offering access and information about science matters. It seems strange to me that I rarely come across similar information from the Canadian government, which makes no great effort to let us know about their (it is most definitely theirs and not ours) science.

Nano regulatory frameworks are everywhere!

The scene around nanotechnology regulatory frameworks has been frantic (by comparison with any other time period during the 3 years I’ve been blogging about nano) in the last month or so. This is my second attempt this month at pulling together information about nanotechnology regulatory frameworks (my June 9, 2011 posting).

I’ll start off slow and easy with this roundup of sorts with a brief look at the international scene, move on to US initiatives, offer a brief comment on the Canadian situation, and wrap up with Europe.

International

Dr. Andrew Maynard at the University of Michigan Risk Science Center (UMRSC) blog has written a commentary about the ISO’s (*International Organization for Standardization) latest set of nanotechnology guidelines in his May 27, 2011 posting.  From the posting,

ISO/TR 31321:2011: Nanotechnologies – Nanomaterial risk evaluation is unashamedly based on the Environmental Defense Fund/DuPont Nano Risk Framework. Much of the structure and content reflects that of the original – a testament to the thought and effort that went into the first document. …The ISO report is written in a much tighter style than that of the original document, and loses some of the occasionally long-winded expositions on what should be done and why. And the ISO document is more compact – 66 pages as opposed to 104. But from a comparative reading, surprisingly little has been changed from the 2007 document.

It’s build around a framework of six steps:

  1. describe materials and applications
  2. material profiles
  3. evaluate risks
  4. assess risk management options
  5. decide, document, and act
  6. review and adapt

From the posting,

Inherent to this framework is the need to make situation-specific decisions that are guided by the Technical Report but not necessarily prescribed by it, and the need to constantly review and revise procedures and decisions. This built-in flexibility and adaptability makes ISO/TR 31321 a powerful tool for developing tailored nanomaterial management strategies that are responsive to new information as it becomes available. It also presents an integrative approach to using materials safely, that deals with the need to make decisions under considerable uncertainty by blurring the line between risk assessment and risk management.

Andrew’s view of these guidelines is largely positive and you can get more details and history by viewing his original commentary. (I first mentioned these new ISO guidelines in my May 18, 2011 posting.)

Sticking with the international scene (in this case, ISO), there was a June 13, 2011 news item on Nanowerk about a new ISO general liability classification for nanotechnology and alternative energy (from the news item),

The new classifications to address the growing use of nanotechnology are Nanomaterial Distributors and Nanomaterial Manufacturing. The once-limited use of nanotechnology in electronics and information technology industries is now swiftly permeating the consumer marketplace, from cosmetics to clothing and more. The Nanomaterial Distributors classification applies to risks that sell nanomaterials to others, and the Nanomaterial Manufacturing classification applies to risks that manufacture or engineer nanomaterials for others.

“With heightened interest to reduce the carbon footprint, establish energy independence, and increase the use of renewable resources, alternative power is a priority for many,” said Beth Fitzgerald, vice president of commercial lines and modeling at ISO. “In response to the growing demand for alternative energy, ISO introduced classifications for risks in three main areas: biofuels, solar energy, and wind energy. The new classifications will allow for future evaluation of the loss experience of those emerging markets.”

The biofuels classifications consist of Biofuels Manufacturing and Biofuels Distributors. Since ethanol already has a widespread and accepted use, a further distinction is made between “ethanol” and “biofuels other than ethanol.”

The solar energy classifications include Solar Energy Farms, Solar Energy Equipment Dealers or Distributors, and Solar Energy Equipment Manufacturing. The wind energy classifications include Wind Turbine Contractors – Installation, Service, or Repair and onshore and offshore Wind Farms.

* I have for many years understood that ISO is the International Standards Organization and I see from a note on the UMRSC blog that these days it is the International Organization for Standardization.

US

On the US front, three different agencies have made announcements that in one way or another will have an impact on the nanotechnology regulatory frameworks in that country.

The White House Emerging Technologies Interagency Policy Coordination Committee (ETIPC) recently released a set of principles for the regulation and oversight of nanotechnology applications and guidance for the development and implementation of policies at the agency level. From the June 9, 2011 news item on Nanowerk,

The realization of nanotechnology’s full potential will require continued research and flexible, science-based approaches to regulation that protect public health and the environment while promoting economic growth, innovation, competitiveness, exports, and job creation.

In furtherance of those goals, the White House Emerging Technologies Interagency Policy Coordination Committee (ETIPC) has developed a set of principles (pdf) specific to the regulation and oversight of applications of nanotechnology, to guide the development and implementation of policies at the agency level.

These principles reinforce a set of overarching principles (pdf) for the regulation and oversight of emerging technologies released on March 11, 2011. They also reflect recommendations from a report on nanotechnology (pdf) by the President’s Council of Advisors on Science and Technology. The report encourages Federal support for the commercialization of nanotech products and calls for the development of rational, science- and risk-based regulatory approaches that would be based on the full array of a material’s properties and their plausible risks and not simply on the basis of size alone.

You can read more about the guidelines at Nanowerk or on the Environemental Expert website here.

Back over on the UMRSC blog, Dr. Andrew Maynard had these comments in his June 13, 2011 posting,

In a joint memorandum, the Office of Science and Technology Policy, the Office of Management and Budget and the Office of the United States Trade Representative laid out Policy Principles for the U.S. Decision Making Concerning Regulations and Oversight of Applications of Nanotechnology and Nanomaterials.

Reading through it, a number of themes emerge, including:

  • Existing regulatory frameworks provide a firm foundation for the oversight of nanomaterials, but there is a need to respond to new scientific evidence on potential risks, and to consider administrative and legal modifications to the regulatory landscape should the need arise.
  • Regulatory action on nanomaterials should be based on scientific evidence of risk, and not on definitions of materials that do not necessarily reflect the evidence-based likelihood of a material causing harm.
  • There should be no prior judgement on whether nanomaterials are intrinsically benign or harmful, in the absence of supporting scientific evidence.
  • Transparency and communication are important to ensuring effective evidence-based regulation.

Overall, this is a strong set of policy principles that lays the groundwork for developing regulation that is grounded in science and not swayed by speculative whims, and yet is responsive and adaptive to emerging challenges. Gratifyingly, the memorandum begins to touch on some of the concerns I have expressed previously about approaches to nanomaterial regulation that seem not to be evidence-based. There is a reasonable chance that they will help move away from the dogma that engineered nanomaterials should be regulated separately because they are new, to a more nuanced and evidence-based approach to ensuring the safe use of increasingly sophisticated materials. Where it perhaps lacks is in recognizing the importance of other factors in addition to science in crafting effective regulation, and in handling uncertainty in decision making.

June 9, 2011 was quite the day as in addition to the White House documents, the US Environmental Protection Agency (EPA) and the US Food and Drug Administration (FDA) both announced public consultations on nanotechnology regulation.

From the June 9, 2011 news item on Nanowerk about the US EPA public consultation,

The U.S. Environmental Protection Agency announced today it plans to obtain information on nanoscale materials in pesticide products. Under the requirements of the law, EPA will gather information on what nanoscale materials are present in pesticide products to determine whether the registration of a pesticide may cause unreasonable adverse effects on the environment and human health. The proposed policy will be open for public comment.

“We want to obtain timely and accurate information on what nanoscale materials may be in pesticide products, “said Steve Owens assistant administrator for EPA’s Office of Chemical Safety and Pollution Prevention. “This information is needed for EPA to meet its requirement under the law to protect public health and the environment.”

Comments on the Federal Register notice will be accepted until 30 days after publication. The notice will be available at www.regulations.gov in docket number EPA–HQ–OPP–2010-0197. More information or to read the proposed notice: http://www.epa.gov/pesticides/regulating/nanotechnology.html [Pesticides; Policies Concerning Products Containing Nanoscale Materials; Opportunity for Public Comment]

The US FDA has taken a more complicated approach to its public consultation with two notices being issued about the same consultation. The June 9, 2011 news item on Nanowerk had this to say,

The U.S. Food and Drug Administration today released draft guidance to provide regulated industries with greater certainty about the use of nanotechnology, which generally involves materials made up of particles that are at least one billionth of a meter in size. The guidance outlines the agency’s view on whether regulated products contain nanomaterials or involve the application of nanotechnology.

The draft guidance, “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology”, is available online and open for public comment. It represents the first step toward providing regulatory clarity on the FDA’s approach to nanotechnology.

Specifically, the agency named certain characteristics – such as the size of nanomaterials used and the exhibited properties of those materials – that may be considered when attempting to identify applications of nanotechnology in regulated products.

“With this guidance, we are not announcing a regulatory definition of nanotechnology,” said Margaret A. Hamburg, MD, Commissioner of Food and Drugs. “However, as a first step, we want to narrow the discussion to these points and work with industry to determine if this focus is an appropriate starting place.”

Then there was a June 15, 2011 news item on Nanowerk offering more details about the draft guidance announcement of June 9, 2011,

The guidelines list things that might be considered when deciding if nanotechnology was used on a product regulated by FDA—including the size of the nanomaterials that were used, and what their properties are.

And FDA wants industry leaders and the public to weigh-in.

Nanotechnology—the science of manipulating materials on a scale so small that it can’t be seen with a regular microscope—could have a broad range of applications, such as increasing the effectiveness of a particular drug or improving the packaging of food or cosmetics. “Nanotechnology is an emerging technology that has the potential to be used in a broad array of FDA-regulated medical products, foods, and cosmetics,” says Carlos Peña, director of FDA’s emerging technology programs. “But because materials in the nanoscale dimension may have different chemical, physical, or biological properties from their larger counterparts, FDA is monitoring the technology to assure such use is beneficial.”

In other words, using nanotechnology can change the way a product looks or operates, Peña says.

Although the technology is still evolving, it’s already in use as display technology for laptop computers, cell phones, and digital cameras. In the medical community, a number of manufacturers have used nanotechnology in:

  • Drugs
  • Medical imaging
  • Antimicrobial materials
  • Medical devices
  • Sunscreens

Andrew Maynard in his previously noted June 13, 2011 posting on on the UMRSC blog had this to say  about the EPA’s draft document,

This is a long and somewhat convoluted document, that spends some time outlining what the agency considers is an engineered nanomaterial, and reviewing nanomaterial hazard data.

Reading the document, EPA still seems somewhat tangled up with definitions of engineered nanomaterials. After outlining conventional attributes associated with engineered nanomaterials, including structures between ~1 – 100 nm and unique or novel properties, the document states,

“These elements do not readily work in a regulatory context because of the high degree of subjectivity involved with interpreting such phrases as “unique or novel properties” or “manufactured or engineered to take advantage of these properties” Moreover the contribution of these subjective elements to risk has not been established.”

This aligns with where my own thinking has been moving in recent years. Yet following this statement, the document reverts back to considering nanoparticles between 1 – 100 nm as the archetypal nanomaterial, and intimates “novel” properties such as “larger surface area per unit volume and/or quantum effects” as raising new risk concerns.

Canadian segue

I’ll point out here that Health Canada’s Interim Policy definition also adheres to the 1 to 100 nm definition for a nanomaterial, a concern I expressed in my submission to the public consultation held last year. Interestingly, since 29 submissions does seem particularly daunting to read there has yet to be any public response to these submissions. Not even a list of which agencies and individuals made submissions.

Back to US

Andrew also comments on the FDA document,

The FDA Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology is a very different kettle of fish to the EPA document. It is overtly responsive to the White House memo; it demonstrates a deep understanding of the issues surrounding nanotechnology and regulation; and it is mercifully concise.

To be fair, the scope of the draft guidance is limited to helping manufacturers understand how the agency is approaching nanotechnology-enabled products under their purview. But this is something it does well.

One of the more significant aspects of the guidance is the discussion on regulatory definitions of nanomaterials. Following a line of reasoning established some years ago, the agency focuses on material properties rather than rigid definitions:

“FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms… Based on FDA’s current scientific and technical understanding of nanomaterials and their characteristics, FDA believes that evaluations of safety, effectiveness or public health impact of such products should consider the unique properties and behaviors that nanomaterials may exhibit”

I recommend reading the full text of Andrew’s comments.

Europe

Meanwhile, there was a June 10, 2011 news item on Nanowerk about the availability of  28 presentations from a May 10-12, 2011 joint European workshop hosted by the Engineered NanoParticle Risk Assessment (ENPRA) FP (Framework Programme) 7 project and the European Commission’s Joint Research Centre. From the news item about the Challenges of Regulation and Risk Assessment of Nanomaterials workshop,

Twenty-eight presentations delivered at the Joint JRC Nano event and 2nd ENPRA Stakeholders Workshop are now available on-line: ENPRA Workshop 2011 – Programme with Presentations.

The workshop (by invitation only) involved about 90 participants, from industry, government, NGOs, and academia. …

During two days and a half, 34 experts from 26 different organisations informed the participants on the latest scientific progress in the field of nanoparticles risk assessment produced within national and European projects, and first results of ENPRA FP7 project were presented in detail. In addition, recent developments concerning legislation in the EU and beyond were discussed.

Amongst other participants, you can include representatives of EU Associate and Candidate Countries, environment and workers’ protection organisations, CAIQ (Chinese Academy of Inspection and Quarantine), US-EPA, ECHA, and EFSA.

To close this piece (and I want to do that very badly), I’m going to give Tim Harper at his TNT blog (on the Cientifica website) the final word from his June 10, 2011 posting,

The White House Emerging Technologies Interagency Policy Coordination Committee (ETIPC) has developed a set of principles (pdf) specific to the regulation and oversight of applications of nanotechnology, to guide the development and implementation of policies at the agency level.

I’m glad to see that it addresses those two old bugbears, the confusion between risk and hazard and the prejudging of issues without reference to scientific evidence …

It is an approach which appears to diverge slightly from the European adoption of the precautionary principle …

As with any regulation, the problems will arise not from the the original wording, but through its (mis)interpretation and inconsistent application.