Tag Archives: US Food and Drug Administration

FOE, nano, and food: part three of three (final guidance)

The first part of this food and nano ‘debate’ started off with the May 22, 2014 news item on Nanowerk announcing the Friends of the Earth (FOE) report ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture‘. Adding energy to FOE’s volley was a Mother Jones article written by Tom Philpott which had Dr. Andrew Maynard (Director of the University of Michigan’s Risk Science Center) replying decisively in an article published both on Nanowerk and on the Conversation.

The second part of this series focused largely on a couple of  research efforts (a June 11, 2014 news item on Nanowerk highlights a Franco-German research project, SolNanoTox) and in the US (a  June 19, 2014 news item on Azonano about research from the University of Arizona focusing on nanoscale additives for dietary supplement drinks) and noted another activist group’s (As You Sow) initiative with Dunkin’ Donuts (a July 11, 2014 article by Sarah Shemkus in a sponsored section in the UK’s Guardian newspaper0).

This final part in the series highlights the US Food and Drug Administration’s (FDA) final guidance document on nanomaterials and food issued some five weeks after the FOE’s report and an essay by a Canadian academic on the topic of nano and food.

A July 9, 2014 news item on Bloomberg BNA sums up the FDA situation,

The Food and Drug Administration June 24 [2014] announced new guidance to provide greater regulatory clarity for industry on the use of nanotechnology in FDA-regulated products, including drugs, devices, cosmetics and food.

In this final guidance, the agency said that nanotechnology “can be used in a broad array of FDA-regulated products, including medical products (e.g., to increase bioavailability of a drug), foods (e.g., to improve food packaging) and cosmetics (e.g., to affect the look and feel of cosmetics).”

Also on the agency website, the FDA said it “does not make a categorical judgment that nanotechnology is inherently safe or harmful. We intend our regulatory approach to be adaptive and flexible and to take into consideration the specific characteristics and the effects of nanomaterials in the particular biological context of each product and its intended use.”

This July 18, 2014 posting by Jeannie Perron, Miriam Guggenheimm and Allan J. Topol of Covington & Burling LLP on the National Law Review blog provides a better summary and additional insight,

On June 24, 2014, the Food and Drug Administration (FDA) released three final guidance documents addressing the agency’s general approach to nanotechnology and its use by the food and cosmetics industries, as well as a draft guidance on the use of nanomaterials in food for animals.

These guidance documents reflect FDA’s understanding of nanomaterials as an emerging technology of major importance with the potential to be used in novel ways across the entire spectrum of FDA- regulated products.

The documents suggest that FDA plans to approach nanotechnology-related issues cautiously, through an evolving regulatory structure that adapts to manufacturers’ changing uses of this technology. FDA has not established regulatory definitions of “nanotechnology,” “nanomaterial,” “nanoscale,” or other related terms. …

The notion of an “evolving regulatory structure” is very appealing in situations with emerging technologies with high levels of uncertainty. It’s surprising that more of the activist groups don’t see an opportunity with this approach. An organization that hasn’t devised a rigid regulatory structure has no investment in defending it. Activist groups can make the same arguments, albeit from a different perspective, about an emerging technology as the companies do and, theoretically, the FDA has become a neutral party with the power to require a company to prove its products’ safety.

You can find the FDA final guidance and other relevant documents here.

Finally, Sylvain Charlebois, associate dean at the College of Business and Economics at the University of Guelph, offers a rather provocative (and not from the perspective you might expect given his credentials) opinion on the topic of ‘nano and food’  in a July 18, 2014 article for TheRecord.com,

Nanotechnology and nanoparticles have been around for quite some time. In fact, consumers have been eating nanoparticles for years without being aware they are in their food.

Some varieties of Dentyne gum and Jell-O, M&M’s, Betty Crocker whipped cream frosting, Kool-Aid, Pop-Tarts, you name it, contain them. Even food packaging, such as plastic containers and beer bottles, have nanoparticles.

While consumers and interest groups alike are registering their concerns about genetically modified organisms, the growing role of nanotechnology in food and agriculture is impressive. When considering the socio-economic and ethical implications of nanotechnology, comparisons to the genetic modification debate are unavoidable.

The big picture is this. For years, capitalism has demonstrated its ability to create wealth while relying on consumers’ willingness to intrinsically trust what is being offered to them. With trans fats, genetically modified organisms and now nanoparticles, our food industry is literally playing with fire. [emphasis mine]

Most consumers may not have the knowledge to fully comprehend the essence of what nanotechnology is or what it can do. However, in an era where data access in almost constant real-time is king, the industry should at least give public education a shot.

In the end and despite their tactics, the activist groups do have a point. The food and agricultural industries need to be more frank about what they’re doing with our food. As Charlebois notes, they might want to invest in some public education, perhaps taking a leaf out of the Irish Food Board’s book and presenting the public with information both flattering and nonflattering about their efforts with our food.

Part one (an FOE report is published)

Part two (the problem with research)

ETA Aug. 22, 2014: Coincidentally, Michael Berger has written an Aug. 22, 2014 Nanowerk Spotlight article titled: How to identify nanomaterials in food.

ETA Sept. 1, 2014: Even more coincidentally, Michael Berger has written a 2nd Nanowerk Spotlight (dated Aug. 25, 2014) on the food and nano topic titled, ‘Nanotechnology in Agriculture’ based on the European Union’s Joint Research Centre’s ‘Workshop on Nanotechnology for the agricultural sector: from research to the field”, held on November 21-22 2013′.

Nanotechnology, tobacco plants, and the Ebola virus

Before presenting information about the current Ebola crisis and issues with vaccines and curatives, here’s a description of the disease from its Wikipedia entry,

Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) is a disease of humans and other primates caused by an ebola virus. Symptoms start two days to three weeks after contracting the virus, with a fever, sore throat, muscle pain, and headaches. Typically nausea, vomiting, and diarrhea follow, along with decreased functioning of the liver and kidneys. Around this time, affected people may begin to bleed both within the body and externally. [1]

As for the current crisis in countries situated on the west coast of the African continent, there’s this from an Aug. 14, 2014 news item on ScienceDaily,

The outbreak of Ebola virus disease that has claimed more than 1,000 lives in West Africa this year poses a serious, ongoing threat to that region: the spread to capital cities and Nigeria — Africa’s most populous nation — presents new challenges for healthcare professionals. The situation has garnered significant attention and fear around the world, but proven public health measures and sharpened clinical vigilance will contain the epidemic and thwart a global spread, according to a new commentary by Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Dr. Fauci’s Aug. 13, 2014 commentary (open access) in the New England Journal of Medicine provides more detail (Note: A link has been removed),

An outbreak of Ebola virus disease (EVD) has jolted West Africa, claiming more than 1000 lives since the virus emerged in Guinea in early 2014 (see figure) Ebola Virus Cases and Deaths in West Africa (Guinea, Liberia, Nigeria, and Sierra Leone), as of August 11, 2014 (Panel A), and Over Time (Panel B).). The rapidly increasing numbers of cases in the African countries of Guinea, Liberia, and Sierra Leone have had public health authorities on high alert throughout the spring and summer. More recent events including the spread of EVD to Nigeria (Africa’s most populous country) and the recent evacuation to the United States of two American health care workers with EVD have captivated the world’s attention and concern. Health professionals and the general public are struggling to comprehend these unfolding dynamics and to separate misinformation and speculation from truth.

In early 2014, EVD emerged in a remote region of Guinea near its borders with Sierra Leone and Liberia. Since then, the epidemic has grown dramatically, fueled by several factors. First, Guinea, Sierra Leone, and Liberia are resource-poor countries already coping with major health challenges, such as malaria and other endemic diseases, some of which may be confused with EVD. Next, their borders are porous, and movement between countries is constant. Health care infrastructure is inadequate, and health workers and essential supplies including personal protective equipment are scarce. Traditional practices, such as bathing of corpses before burial, have facilitated transmission. The epidemic has spread to cities, which complicates tracing of contacts. Finally, decades of conflict have left the populations distrustful of governing officials and authority figures such as health professionals. Add to these problems a rapidly spreading virus with a high mortality rate, and the scope of the challenge becomes clear.

Although the regional threat of Ebola in West Africa looms large, the chance that the virus will establish a foothold in the United States or another high-resource country remains extremely small. Although global air transit could, and most likely will, allow an infected, asymptomatic person to board a plane and unknowingly carry Ebola virus to a higher-income country, containment should be readily achievable. Hospitals in such countries generally have excellent capacity to isolate persons with suspected cases and to care for them safely should they become ill. Public health authorities have the resources and training necessary to trace and monitor contacts. Protocols exist for the appropriate handling of corpses and disposal of biohazardous materials. In addition, characteristics of the virus itself limit its spread. Numerous studies indicate that direct contact with infected bodily fluids — usually feces, vomit, or blood — is necessary for transmission and that the virus is not transmitted from person to person through the air or by casual contact. Isolation procedures have been clearly outlined by the Centers for Disease Control and Prevention (CDC). A high index of suspicion, proper infection-control practices, and epidemiologic investigations should quickly limit the spread of the virus.

Fauci’s article makes it clear that public concerns are rising in the US and I imagine that’s true of Canada too and many other parts of the world, not to mention the countries currently experiencing the EVD outbreak. In the midst of all this comes a US Food and Drug Administration (FDA) warning as per an Aug. 15, 2014 news item (originated by Reuters reporter Toni Clarke) on Nanowerk,

The U.S. Food and Drug Administration said on Thursday [Aug. 14, 2014] it has become aware of products being sold online that fraudulently claim to prevent or treat Ebola.

The FDA’s warning comes on the heels of comments by Nigeria’s top health official, Onyebuchi Chukwu, who reportedly said earlier Thursday [Aug. 14, 2014] that eight Ebola patients in Lagos, the country’s capital, will receive an experimental treatment containing nano-silver.

Erica Jefferson, a spokeswoman for the FDA, said she could not provide any information about the product referenced by the Nigerians.

The Aug. 14,  2014 FDA warning reads in part,

The U.S. Food and Drug Administration is advising consumers to be aware of products sold online claiming to prevent or treat the Ebola virus. Since the outbreak of the Ebola virus in West Africa, the FDA has seen and received consumer complaints about a variety of products claiming to either prevent the Ebola virus or treat the infection.

There are currently no FDA-approved vaccines or drugs to prevent or treat Ebola. Although there are experimental Ebola vaccines and treatments under development, these investigational products are in the early stages of product development, have not yet been fully tested for safety or effectiveness, and the supply is very limited. There are no approved vaccines, drugs, or investigational products specifically for Ebola available for purchase on the Internet. By law, dietary supplements cannot claim to prevent or cure disease.

As per the FDA’s reference to experimental vaccines, an Aug. 6, 2014 article by Caroline Chen, Mark Niquette, Mark Langreth, and Marie French for Bloomberg describes the ZMapp vaccine/treatment (Note: Links have been removed),

On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.

The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.

Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.

Researchers try to identify the best antibodies in the lab, before testing them on mice, then eventually on monkeys. Mapp’s experimental drug, dubbed ZMapp, has three antibodies, which work together to alert the immune system and neutralize the Ebola virus, she [Erica Ollman Saphire, a molecular biologist at the Scripps Research Institute,] said.

This is where the tobacco comes in: the plants are used as hosts to grow large amounts of the antibodies. Genes for the desired antibodies are fused to genes for a natural tobacco virus, Charles Arntzen, a plant biotechnology expert at Arizona State University, said in an Aug. 4 [2014] telephone interview.

The tobacco plants are then infected with this new artificial virus, and antibodies are grown inside the plant. Eventually, the tobacco is ground up and the antibody is extracted, Arntzen said.

The process of growing antibodies in mammals risks transferring viruses that could infect humans, whereas “plants are so far removed, so if they had some sort of plant virus we wouldn’t get sick because viruses are host-specific,” said Qiang Chen, a plant biologist at Arizona State University in Tempe, Arizona, in a telephone interview.

There is a Canadian (?) company working on a tobacco-based vaccines including one for EVD but as the Bloomberg writers note the project is highly secret,

Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris. [emphasis mine]

Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview.

The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.

Medicago ‘‘is currently closely working with partners for the production of an Ebola antibody as well as other antibodies that are of interest for bio-defense,” he said in an e-mail. He would not disclose who the partners were. [emphasis mine]

I have checked both the English and French language versions of Medicago’s website and cannot find any information about their work on ebola. (The Bloomberg article provides a good overview of the ebola situation and more. I recommend reading it and/or the Aug. 15, 2014 posting on CTV [Canadian Television Network] which originated from an Associated Press article by Malcolm Ritter).

Moving on to more research and ebola, Dexter Johnson in an Aug. 14, 2014 posting (on his Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] website,) describes some work from Northeastern University (US), Note: Links have been removed,

With the Ebola virus death toll now topping 1000 and even the much publicized experimental treatment ZMapp failing to save the life of a Spanish missionary priest who was treated with it, it is clear that scientists need to explore new ways of fighting the deadly disease. For researchers at Northeastern University in Boston, one possibility may be using nanotechnology.

“It has been very hard to develop a vaccine or treatment for Ebola or similar viruses because they mutate so quickly,” said Thomas Webster, the chair of Northeastern’s chemical engineering department, in a press release. “In nanotechnology we turned our attention to developing nanoparticles that could be attached chemically to the viruses and stop them from spreading.”

Webster, along with many researchers in the nanotechnology community, have been trying to use gold nanoparticles, in combination with near-infrared light, to kill cancer cells with heat. The hope is that the same approach could be used to kill the Ebola virus.

There is also an Aug. 6, 2014 Northeastern University news release by Joe O’Connell describing the technique being used by Webster’s team,

… According to Web­ster, gold nanopar­ti­cles are cur­rently being used to treat cancer. Infrared waves, he explained, heat up the gold nanopar­ti­cles, which, in turn, attack and destroy every­thing from viruses to cancer cells, but not healthy cells.

Rec­og­nizing that a larger sur­face area would lead to a quicker heat-​​up time, Webster’s team cre­ated gold nanos­tars. “The star has a lot more sur­face area, so it can heat up much faster than a sphere can,” Web­ster said. “And that greater sur­face area allows it to attack more viruses once they absorb to the par­ti­cles.” The problem the researchers face, how­ever, is making sure the hot gold nanopar­ti­cles attack the virus or cancer cells rather than the healthy cells.

At this point, there don’t seem to be any curative measures generally available although some are available experimentally in very small quantities.

Graphene and an artificial retina

A graphene-based artificial retina project has managed to intermingle the European Union’s two major FET (Future and Emerging Technologies) funding projects, 1B Euros each to be disbursed over 10 years, the Graphene Flagship and the Human Brain Project. From an Aug. 7, 2014 Technische Universitaet Muenchen (TUM) news release (also on EurekAlert),

Because of its unusual properties, graphene holds great potential for applications, especially in the field of medical technology. A team of researchers led by Dr. Jose A. Garrido at the Walter Schottky Institut of the TUM is taking advantage of these properties. In collaboration with partners from the Institut de la Vision of the Université Pierre et Marie Curie in Paris and the French company Pixium Vision, the physicists are developing key components of an artificial retina made of graphene.

Retina implants can serve as optical prostheses for blind people whose optical nerves are still intact. The implants convert incident light into electrical impulses that are transmitted to the brain via the optical nerve. There, the information is transformed into images. Although various approaches for implants exist today, the devices are often rejected by the body and the signals transmitted to the brain are generally not optimal.

Already funded by the Human Brain Project as part of the Neurobotics effort, Garrido and his colleagues will now also receive funding from the Graphene Flagship. As of July 2014, the Graphene Flagship has added 86 new partners including TUM according to the news release.

Here’s an image of an ‘invisible’ graphene sensor (a precursor to developing an artificial retina),

Graphene electronics can be prepared on flexible substrates. Only the gold metal leads are visible in the transparent graphene sensor. (Photo: Natalia Hutanu / TUM)

Graphene electronics can be prepared on flexible substrates. Only the gold metal leads are visible in the transparent graphene sensor. (Photo: Natalia Hutanu / TUM)

Artificial retinas were first featured on this blog in an Aug. 18, 2011 posting about video game Deus Ex: Human Revolution which features a human character with artificial sight. The post includes links to a video of a scientist describing an artificial retina trial with 30 people and an Israeli start-up company, ‘Nano Retina’, along with information about ‘Eyeborg’, a Canadian filmmaker who on losing an eye in an accident had a camera implanted in the previously occupied eye socket.

More recently, a Feb. 15, 2013 posting featured news about the US Food and Drug Administration’s decision to allow sale of the first commercial artificial retinas in the US in the context of news about a neuroprosthetic implant in a rat which allowed it to see in the infrared range, normally an impossible feat.

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.

This looks like an attempt to develop a relationship where the industry players in the food industry 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.

* “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.” changed July 30, 2014 to be more grammatically correct.

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.