Tag Archives: US Food and Drug Administration

$1.4B for US National Nanotechnology Initiative (NNI) in 2017 budget

According to an April 1, 2016 news item on Nanowerk, the US National Nanotechnology (NNI) has released its 2017 budget supplement,

The President’s Budget for Fiscal Year 2017 provides $1.4 billion for the National Nanotechnology Initiative (NNI), affirming the important role that nanotechnology continues to play in the Administration’s innovation agenda. NNI
Cumulatively totaling nearly $24 billion since the inception of the NNI in 2001, the President’s 2017 Budget supports nanoscale science, engineering, and technology R&D at 11 agencies.

Another 9 agencies have nanotechnology-related mission interests or regulatory responsibilities.

An April 1, 2016 NNI news release, which originated the news item, affirms the Obama administration’s commitment to the NNI and notes the supplement serves as an annual report amongst other functions,

Throughout its two terms, the Obama Administration has maintained strong fiscal support for the NNI and has implemented new programs and activities to engage the broader nanotechnology community to support the NNI’s vision that the ability to understand and control matter at the nanoscale will lead to new innovations that will improve our quality of life and benefit society.

This Budget Supplement documents progress of these participating agencies in addressing the goals and objectives of the NNI. It also serves as the Annual Report for the NNI called for under the provisions of the 21st Century Nanotechnology Research and Development Act of 2003 (Public Law 108-153, 15 USC §7501). The report also addresses the requirement for Department of Defense reporting on its nanotechnology investments, per 10 USC §2358.

For additional details and to view the full document, visit www.nano.gov/2017BudgetSupplement.

I don’t seem to have posted about the 2016 NNI budget allotment but 2017’s $1.4B represents a drop of $100M since 2015’s $1.5 allotment.

The 2017 NNI budget supplement describes the NNI’s main focus,

Over the past year, the NNI participating agencies, the White House Office of Science and Technology Policy (OSTP), and the National Nanotechnology Coordination Office (NNCO) have been charting the future directions of the NNI, including putting greater focus on promoting commercialization and increasing education and outreach efforts to the broader nanotechnology community. As part of this effort, and in keeping with recommendations from the 2014 review of the NNI by the President’s Council of Advisors for Science and Technology, the NNI has been working to establish Nanotechnology-Inspired Grand Challenges, ambitious but achievable goals that will harness nanotechnology to solve National or global problems and that have the potential to capture the public’s imagination. Based upon inputs from NNI agencies and the broader community, the first Nanotechnology-Inspired Grand Challenge (for future computing) was announced by OSTP on October 20, 2015, calling for a collaborative effort to “create a new type of computer that can proactively interpret and learn from data, solve unfamiliar problems using what it has learned, and operate with the energy efficiency of the human brain.” This Grand Challenge has generated broad interest within the nanotechnology community—not only NNI agencies, but also industry, technical societies, and private foundations—and planning is underway to address how the agencies and the community will work together to achieve this goal. Topics for additional Nanotechnology-Inspired Grand Challenges are under review.

Interestingly, it also offers an explanation of the images on its cover (Note: Links have been removed),

US_NNI_2017_budget_cover

About the cover

Each year’s National Nanotechnology Initiative Supplement to the President’s Budget features cover images illustrating recent developments in nanotechnology stemming from NNI activities that have the potential to make major contributions to National priorities. The text below explains the significance of each of the featured images on this year’s cover.

US_NNI_2017_front_cover_CloseUp

Front cover featured images (above): Images illustrating three novel nanomedicine applications. Center: microneedle array for glucose-responsive insulin delivery imaged using fluorescence microscopy. This “smart insulin patch” is based on painless microneedles loaded with hypoxia-sensitive vesicles ~100 nm in diameter that release insulin in response to high glucose levels. Dr. Zhen Gu and colleagues at the University of North Carolina (UNC) at Chapel Hill and North Carolina State University have demonstrated that this patch effectively regulates the blood glucose of type 1 diabetic mice with faster response than current pH-sensitive formulations. The inset image on the lower right shows the structure of the nanovesicles; each microneedle contains more than 100 million of these vesicles. The research was supported by the American Diabetes Association, the State of North Carolina, the National Institutes of Health (NIH), and the National Science Foundation (NSF). Left: colorized rendering of a candidate universal flu vaccine nanoparticle. The vaccine molecule, developed at the NIH Vaccine Research Center, displays only the conserved part of the viral spike and stimulates the production of antibodies to fight against the ever-changing flu virus. The vaccine is engineered from a ~13 nm ferritin core (blue) combined with a 7 nm influenza antigen (green). Image credit: NIH National Institute of Allergy and Infectious Diseases (NIAID). Right: colorized scanning electron micrograph of Ebola virus particles on an infected VERO E6 cell. Blue represents individual Ebola virus particles. The image was produced by John Bernbaum and Jiro Wada at NIAID. When the Ebola outbreak struck in 2014, the Food and Drug Administration authorized emergency use of lateral flow immunoassays for Ebola detection that use gold nanoparticles for visual interpretation of the tests.

US_NNI_2017_back_cover._CloseUp

Back cover featured images (above): Images illustrating examples of NNI educational outreach activities. Center: Comic from the NSF/NNI competition Generation Nano: Small Science Superheroes. Illustration by Amina Khan, NSF. Left of Center: Polymer Nanocone Array (biomimetic of antimicrobial insect surface) by Kyle Nowlin, UNC-Greensboro, winner from the first cycle of the NNI’s student image contest, EnvisioNano. Right of Center: Gelatin Nanoparticles in Brain (nasal delivery of stroke medication to the brain) by Elizabeth Sawicki, University of Illinois at Urbana-Champaign, winner from the second cycle of EnvisioNano. Outside right: still photo from the video Chlorination-less (water treatment method using reusable nanodiamond powder) by Abelardo Colon and Jennifer Gill, University of Puerto Rico at Rio Piedras, the winning video from the NNI’s Student Video Contest. Outside left: Society of Emerging NanoTechnologies (SENT) student group at the University of Central Florida, one of the initial nodes in the developing U.S. Nano and Emerging Technologies Student Network; photo by Alexis Vilaboy.

A couple of lawyers talk wrote about managing nanotechnology risks

Because they are lawyers, I was intrigued by a Nov. 4, 2015 article on managing nanotechnology risks by Michael Lisak and James Mizgala of Sidley Austin LLP for Industry Week. I was also intrigued by the language (Note: A link has been removed),

The inclusion of nanotechnologies within manufacturing processes and products has increased exponentially over the past decade. Fortune recently noted that nanotechnology touches almost all Fortune 500 companies and that the industry’s $20 billion worldwide size is expected to double over the next decade. [emphasis mine]

Yet, potential safety issues have been raised and regulatory uncertainties persist. As such, proactive manufacturers seeking to protect their employees, consumers, the environment and their businesses – while continuing to develop, manufacture and market their products – may face difficult choices in how to best navigate this challenging and fluid landscape, while avoiding potential “nanotort,”  [emphasis mine] whistleblower, consumer fraud and regulatory enforcement lawsuits. Doing so requires forward-thinking advice based upon detailed analyses of each manufacturer’s products and conduct in the context of rapidly evolving scientific, regulatory and legal developments.

I wonder how many terms lawyers are going to coin in addition to “nanotort”?

The lawyers focus largely on two types of nanoparticles, carbon nanotubes, with a special emphasis on multi-walled carbon nantubes (MWCNT) and nano titanium dioxide,

Despite this scientific uncertainty, international organizations, such as the International Agency for Research on Cancer [a World Health Organization agency], have already concluded that nano titanium dioxide in its powder form and multi-walled carbon nanotube-7 (“MWCNT-7”) [emphasis mine] are “possibly carcinogenic to humans.” As such, California’s Department of Public Health lists titanium dioxide and MWCNT-7 as “ingredients known or suspected to cause cancer, birth defects, or other reproductive toxicity as determined by the authoritative scientific bodies.”  Considering that processed (i.e., non-powdered) titanium dioxide is found in products like toothpaste, shampoo, chewing gum and candies, it is not surprising that some have focused upon such statements.

There’s a lot of poison in the world, for example, apples contain seeds which have arsenic in them and, for another, peanuts can be carcinogenic and they can also kill you, as they are poison to people who are allergic to them.

On the occasion of Dunkin’ Donuts removing nano titanium dioxide as an ingredient in the powdered sugar used to coat donuts, I wrote a March 13, 2015 posting, where I quote extensively from Dr. Andrew Maynard’s (then director of the University of Michigan Risk Science Center now director of the Risk Innovation Lab at Arizona State University) 2020 science blog posting about nano titanium dioxide and Dunkin’ Donuts,

He describes some of the research on nano titanium dioxide (Note: Links have been removed),

… In 2004 the European Food Safety Agency carried out a comprehensive safety review of the material. After considering the available evidence on the same materials that are currently being used in products like Dunkin’ Donuts, the review panel concluded that there no evidence for safety concerns.

Most research on titanium dioxide nanoparticles has been carried out on ones that are inhaled, not ones we eat. Yet nanoparticles in the gut are a very different proposition to those that are breathed in.

Studies into the impacts of ingested nanoparticles are still in their infancy, and more research is definitely needed. Early indications are that the gastrointestinal tract is pretty good at handling small quantities of these fine particles. This stands to reason given the naturally occurring nanoparticles we inadvertently eat every day, from charred foods and soil residue on veggies and salad, to more esoteric products such as clay-baked potatoes. There’s even evidence that nanoparticles occur naturally inside the gastrointestinal tract.

You can find Andrew’s entire discussion in his March 12, 2015 post on the 2020 Science blog. Andrew had written earlier in a July 12, 2014 posting about something he terms ‘nano donut math’ as reported by As You Sow, the activist group that made a Dunkin’ Donuts shareholder proposal which resulted in the company’s decision to stop using nano titanium dioxide in the powdered sugar found on their donuts. In any event, Andrew made this point,

In other words, if a Dunkin’ Donut Powdered Cake Donut contained 8.9 mg of TiO2 particles smaller than 10 nm, it would have to have been doused with over 1 million tons of sugar coating! (Note update at the end of this piece)

Clearly something’s wrong here – either Dunkin’ Donuts are not using food grade TiO2 but a nanopowder with particle so small they would be no use whatsoever in the sugar coating (as well as being incredibly expensive, and not FDA approved).  Or there’s something rather wrong with the analysis!

If it’s the latter – and it’s hard to imagine any other plausible reason for the data – it looks like As You Sow ended up using rather dubious figures to back up their stakeholder resolution.  I’d certainly be interested in more information on the procedures Analytical Sciences used and the checks and balances they had in place, especially as there are a number of things that can mess up a particle analysis like this.

Update July 14: My bad, I made a slight error in the size distribution calculation first time round.  This has been corrected in the article above.  Originally, I cited the estimated Mass Median Diameter (MMD) of the TiO2 particles as 167 nm, and the Geometric Standard Deviation (GSD) as 1.6.  Correcting an error in the Excel spreadsheet used to calculate the distribution (these things happen!) led to a revised estimate of MMD = 168 nm and a GSD of 1.44.  These may look like subtle differences, but when calculating the estimated particle mass below 10 nm, they make a massive difference.  With the revised figures, you’d expect less than one trillionth of  a percent of the mass of the TiO2 powder to be below 10 nm!! (the original estimate was a tenth of a millionth of a percent).  In other words – pretty much nothing!  The full analysis can be found here.

Update November 16 2014.  Based on this post, As You Sow checked the data from Analytical Sciences LLC and revised the report accordingly.  This is noted above.

It would seem that if there are concerns over nano titanium dioxide in food, the biggest would not be the amounts ingested by consumers but inhalation by workers should they breathe in large quantities when they are handling the material.

As for the MWCNTs, they have long raised alarms but most especially the long MWCNTs and for people handling them during the course of their work day. Any MWCNTs found in sports equipment and other consumer products are bound in the material and don’t pose any danger of being inhaled into the lungs, unless they should be released from their bound state (e.g. fire might release them).

After some searching for MWCNT-7, I found something which seems also to be known as Mitsui MWCNT-7 or Mitsui 7-MWCNT (here’s one of my sources). As best I understand it, Mitsui is a company that produces an MWCNT which they have coined an MWCNT-7 and which has been used in nanotoxicity testing. As best I can tell, MWCNT is MWCNT-7.

The lawyers (Lisak and Mizgala) note things have changed for manufacturers since the early days and they make some suggestions,

One thing is certain – gone are the days when “sophisticated” manufacturers incorporating nanotechnologies within their products can reasonably expect to shield themselves by pointing to scientific and regulatory uncertainties, especially given the amount of money they are spending on research and development, as well as sales and marketing efforts.

Accordingly, manufacturers should consider undertaking meaningful risk management analyses specific to their applicable products. …

First, manufacturers should fully understand the life-cycle of nanomaterials within their organization. For some, nanomaterials may be an explicit focus of innovation and production, making it easier to pinpoint where nanotechnology fits into their processes and products. For others, nanomaterials may exist either higher-up or in the back-end of their products’ supply chain. …

Second, manufacturers should understand and stay current with the scientific state-of-the-art as well as regulatory requirements and developments potentially applicable to their employees, consumers and the environment. An important consideration related to efforts to understand the state-of-the-art is whether or not manufacturers should themselves expend resources to advance “the science” in seeking to help find answers to some of the aforementioned uncertainties. …

The lawyers go on to suggest that manufacturers should consider proactively researching nanotoxicity so as to better defend themselves against any future legal suits.

Encouraging companies to proactive with toxicity issues is in line with what seems to be an international (Europe & US) regulatory movement putting more onus on producers and manufacturers to take responsibility for safety testing. (This was communicated to me in a conversation I had with an official at the European Union Joint Research Centre where he mentioned REACH regulations and the new emphasis in response to my mention of similar FDA (US Food and Drug Administration) regulations. (We were at the 2014 9th World Congress on Alternatives to Animal Testing in Prague, Czech republic.)

For anyone interested in the International Agency for Research on Cancer you can find it here.

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

ETA July 22, 2015: I now have a link to the magazine article.

Clinical trial for bionic eye (artificial retinal implant) shows encouraging results (safety and efficacy)

The Argus II artificial retina was first mentioned here in a Feb. 15, 2013 posting (scroll down about 50% of the way) when it received US Food and Drug Administration (FDA) commercial approval. In retrospect that seems puzzling since the results of a three-year clinical trial have just been reported in a June 23, 2015 news item on ScienceDaily (Note: There was one piece of information about the approval which didn’t make its way into the information disseminated in 2013),

The three-year clinical trial results of the retinal implant popularly known as the “bionic eye,” have proven the long-term efficacy, safety and reliability of the device that restores vision in those blinded by a rare, degenerative eye disease. The findings show that the Argus II significantly improves visual function and quality of life for people blinded by retinitis pigmentosa. They are being published online in Ophthalmology, the journal of the American Academy of Ophthalmology.

A June 23, 2015 American Academy of Ophthalmology news release (also on EurekAlert), which originated the news item, describes the condition the Argus II is designed for and that crucial bit of FDA information,

Retinitis pigmentosa is an incurable disease that affects about 1 in 4,000 Americans and causes slow vision loss that eventually leads to blindness.[1] The Argus II system was designed to help provide patients who have lost their sight due to the disease with some useful vision. Through the device, patients with retinitis pigmentosa are able to see patterns of light that the brain learns to interpret as an image. The system uses a miniature video camera stored in the patient’s glasses to send visual information to a small computerized video processing unit which can be stored in a pocket. This computer turns the image to electronic signals that are sent wirelessly to an electronic device implanted on the retina, the layer of light-sensing cells lining the back of the eye.

The Argus II received Food and Drug Administration (FDA) approval as a Humanitarian Use Device (HUD) in 2013, which is an approval specifically for devices intended to benefit small populations and/or rare conditions. [emphasis mine]

I don’t recall seeing “Humanitarian Use Device (HUD)” in the 2013 materials which focused on the FDA’s commercial use approval. I gather from this experience that commercial use doesn’t necessarily mean they’ve finished with clinical trials and are ready to start selling the product. In any event, I will try to take a closer look at the actual approvals the next time, assuming I can make sense of the language.

After all the talk about it, here’s what the device looks like,

 Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system. Credit: Photo courtesy of Second Sight Medical Products, Inc.


Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system.
Credit: Photo courtesy of Second Sight Medical Products, Inc.

The news release offers more details about the recently completed clinical trial,

To further evaluate the safety, reliability and benefit of the device, a clinical trial of 30 people, aged 28 to 77, was conducted in the United States and Europe. All of the study participants had little or no light perception in both eyes. The researchers conducted visual function tests using both a computer screen and real-world conditions, including finding and touching a door and identifying and following a line on the ground. A Functional Low-vision Observer Rated Assessment (FLORA) was also performed by independent visual rehabilitation experts at the request of the FDA to assess the impact of the Argus II system on the subjects’ everyday lives, including extensive interviews and tasks performed around the home.

The visual function results indicated that up to 89 percent of the subjects performed significantly better with the device. The FLORA found that among the subjects, 80 percent received benefit from the system when considering both functional vision and patient-reported quality of life, and no subjects were affected negatively.

After one year, two-thirds of the subjects had not experienced device- or surgery-related serious adverse events. After three years, there were no device failures. Throughout the three years, 11 subjects experienced serious adverse events, most of which occurred soon after implantation and were successfully treated. One of these treatments, however, was to remove the device due to recurring erosion after the suture tab on the device became damaged.

“This study shows that the Argus II system is a viable treatment option for people profoundly blind due to retinitis pigmentosa – one that can make a meaningful difference in their lives and provides a benefit that can last over time,” said Allen C. Ho, M.D., lead author of the study and director of the clinical retina research unit at Wills Eye Hospital. “I look forward to future studies with this technology which may make possible expansion of the intended use of the device, including treatment for other diseases and eye injuries.”

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

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind by Allen C. Ho,Mark S. Humayun, Jessy D. Dorn, Lyndon da Cruz, Gislin Dagnelie,James Handa, Pierre-Olivier Barale, José-Alain Sahel, Paulo E. Stanga, Farhad Hafezi, Avinoam B. Safran, Joel Salzmann, Arturo Santos, David Birch, Rand Spencer, Artur V. Cideciyan, Eugene de Juan, Jacque L. Duncan, Dean Eliott, Amani Fawzi, Lisa C. Olmos de Koo, Gary C. Brown, Julia A. Haller, Carl D. Regillo, Lucian V. Del Priore, Aries Arditi, Duane R. Geruschat, Robert J. Greenberg. Opthamology, June 2015 http://dx.doi.org/10.1016/j.ophtha.2015.04.032

This paper is open access.

Dunkin’ Donuts and nano titanium dioxide

It’s been a busy few days for titanium dioxide, nano and otherwise, as the news about its removal from powdered sugar in Dunkin’ Donuts products ripples through the nano blogosphere. A March 6, 2015 news item on Azonano kicks off the discussion with an announcement,

Dunkin’ Brands, the parent company of the Dunkin’ Donuts chain, has agreed to remove titanium dioxide, a whitening agent that is commonly a source of nanomaterials, from all powdered sugar used to make the company’s donuts. As a result of this progress, the advocacy group As You Sow has withdrawn a shareholder proposal asking Dunkin’ to assess and reduce the risks of using nanomaterials in its food products.

Here’s a brief recent history of Dunkin’ Donuts and nano titanium dioxide from my Aug. 21, 2014 posting titled, FOE, nano, and food: part two of three (the problem with research),

Returning to the ‘debate’, a July 11, 2014 article by Sarah Shemkus for a sponsored section in the UK’s Guardian newspaper highlights an initiative taken by an environmental organization, As You Sow, concerning titanium dioxide in Dunkin’ Donuts’ products (Note: A link has been removed),

The activists at environmental nonprofit As You Sow want you to take another look at your breakfast doughnut. The organization recently filed a shareholder resolution asking Dunkin’ Brands, the parent company of Dunkin’ Donuts, to identify products that may contain nanomaterials and to prepare a report assessing the risks of using these substances in foods.

Their resolution received a fair amount of support: at the company’s annual general meeting in May, 18.7% of shareholders, representing $547m in investment, voted for it. Danielle Fugere, As You Sow’s president, claims that it was the first such resolution to ever receive a vote. Though it did not pass, she says that she is encouraged by the support it received.

“That’s a substantial number of votes in favor, especially for a first-time resolution,” she says.

The measure was driven by recent testing sponsored by As You Sow, which found nanoparticles of titanium dioxide in the powdered sugar that coats some of the donut chain’s products. [emphasis mine] An additive widely used to boost whiteness in products from toothpaste to plastic, microscopic titanium dioxide has not been conclusively proven unsafe for human consumption. Then again, As You Sow contends, there also isn’t proof that it is harmless.

“Until a company can demonstrate the use of nanomaterials is safe, we’re asking companies either to not use them or to provide labels,” says Fugere. “It would make more sense to understand these materials before putting them in our food.”

As I understand it, Dunkin’ Donuts will be removing all titanium dioxide, nano-sized or other, from powdered sugar used in its products. It seems As You Sow’s promise to withdraw its July 2104 shareholder resolution is the main reason for Dunkin’ Donuts’ decision. While I was and am critical of Dunkin’ Donuts’ handling of the situation with As You Sow, I am somewhat distressed that the company seems to have acquiesced on the basis of research which is, at best, inconclusive.

Dr. Andrew Maynard, director of the University of Michigan Risk Science Centre, has written a substantive analysis of the current situation regarding nano titanium dioxide in a March 12, 2015 post on his 2020 Science blog (Note: Links have been removed),

Titanium dioxide (which isn’t the same thing as the metal titanium) is an inert, insoluble material that’s used as a whitener in everything from paper and paint to plastics. It’s the active ingredient in many mineral-based sunscreens. And as a pigment, is also used to make food products look more appealing.

Part of the appeal to food producers is that titanium dioxide is a pretty dull chemical. It doesn’t dissolve in water. It isn’t particularly reactive. It isn’t easily absorbed into the body from food. And it doesn’t seem to cause adverse health problems. It just seems to do what manufacturers want it to do – make food look better. It’s what makes the powdered sugar coating on donuts appear so dense and snow white. Titanium dioxide gives it a boost.

And you’ve probably been consuming it for years without knowing. In the US, the Food and Drug Administration allows food products to contain up to 1% food-grade titanium dioxide without the need to include it on the ingredient label. Help yourself to a slice of bread, a bar of chocolate, a spoonful of mayonnaise or a donut, and chances are you’ll be eating a small amount of the substance.

Andrew goes on to describe the concerns that groups such as You As Sow have (Note: Links have been removed),

For some years now, researchers have recognized that some powders become more toxic the smaller the individual particles are, and titanium dioxide is no exception. Pigment grade titanium dioxide – the stuff typically used in consumer products and food – contains particles around 200 nanometers in diameter, or around one five hundredth the width of a human hair. Inhale large quantities of these titanium dioxide particles (I’m thinking “can’t see your hand in front of your face” quantities), and your lungs would begin to feel it.

If the particles are smaller though, it takes much less material to cause the same effect.

But you’d still need to inhale very large quantities of the material for it to be harmful. And while eating a powdered donut can certainly be messy, it’s highly unlikely that you’re going to end up stuck in a cloud of titanium dioxide-tinted powdered sugar coating!

… Depending on what they are made of and what shape they are, research has shown that some nanoparticles are capable of getting to parts of the body that are inaccessible to larger particles. And some particles are more chemically reactive because of their small size. Some may cause unexpected harm simply because they are small enough to throw a nano-wrench into the nano-workings of your cells.

This body of research is why organizations like As You Sow have been advocating caution in using nanoparticles in products without appropriate testing – especially in food. But the science about nanoparticles isn’t as straightforward as it seems.

As Andrew notes,

First of all, particles of the same size but made of different materials can behave in radically different ways. Assuming one type of nanoparticle is potentially harmful because of what another type does is the equivalent of avoiding apples because you’re allergic to oysters.

He describes some of the research on nano titanium dioxide (Note: Links have been removed),

… In 2004 the European Food Safety Agency carried out a comprehensive safety review of the material. After considering the available evidence on the same materials that are currently being used in products like Dunkin’ Donuts, the review panel concluded that there no evidence for safety concerns.

Most research on titanium dioxide nanoparticles has been carried out on ones that are inhaled, not ones we eat. Yet nanoparticles in the gut are a very different proposition to those that are breathed in.

Studies into the impacts of ingested nanoparticles are still in their infancy, and more research is definitely needed. Early indications are that the gastrointestinal tract is pretty good at handling small quantities of these fine particles. This stands to reason given the naturally occurring nanoparticles we inadvertently eat every day, from charred foods and soil residue on veggies and salad, to more esoteric products such as clay-baked potatoes. There’s even evidence that nanoparticles occur naturally inside the gastrointestinal tract.

He also probes the issue’s, nanoparticles, be they titanium dioxide or otherwise, and toxicity, complexity (Note: Links have been removed),

There’s a small possibility that we haven’t been looking in the right places when it comes to possible health issues. Maybe – just maybe – there could be long term health problems from this seemingly ubiquitous diet of small, insoluble particles that we just haven’t spotted yet. It’s the sort of question that scientists love to ask, because it opens up new avenues of research. It doesn’t mean that there is an issue, just that there is sufficient wiggle room in what we don’t know to ask interesting questions.

… While there is no evidence of a causal association between titanium dioxide in food and ill health, some studies – but not all by any means – suggest that large quantities of titanium dioxide nanoparticles can cause harm if they get to specific parts of the body.

For instance, there are a growing number of published studies that indicate nanometer sized titanium dioxide particles may cause DNA damage at high concentrations if it can get into cells. But while these studies demonstrate the potential for harm to occur, they lack information on how much material is needed, and under what conditions, for significant harm. And they tend to be associated with much larger quantities of material than anyone is likely to be ingesting on a regular basis.

They are also counterbalanced by studies that show no effects, indicating that there is still considerable uncertainty over the toxicity or otherwise of the material. It’s as if we’ve just discovered that paper can cause cuts, but we’re not sure yet whether this is a minor inconvenience or potentially life threatening. In the case of nanoscale titanium dioxide, it’s the classic case of “more research is needed.”

I strongly suggest reading Andrew’s post in its entirety either here on the University of Michigan website or here on The Conversation website.

Dexter Johnson in a March 11, 2015 post on his Nanoclast blog also weighs in on the discussion. He provides a very neat summary of the issues along with these observations (Note Links have been removed),

With decades of TiO2 being in our food supply and no reports of toxic reactions, it would seem that the threshold for proof is extremely high, especially when you combine the term “nano” with “asbestos”.

As You Sow makes sure to point out that asbestos is a nanoparticle. While the average diameter of an asbestos fiber is around 20 to 90 nm, their lengths varied between 200 nm and 200 micrometers.

The toxic aspect of asbestos was not its diameter, but its length. …

In addition to his summary Dexter highlights As You Sows attempt to link titanium dioxide nanoparticles to asbestos. I suggest reading his post for an informed description of what made asbestos so toxic (here) and why the linkage seems specious at this time.

For anyone interested in how As You Sow managed to introduce asbestos toxicity issues into a discussion about nano titanium dioxide and food products, there’s this from As You Sow’s FAQs (frequently asked questions) about nanomaterials in food page,

Why are nanomaterials in food important to investors?

When technology is used before ensuring that it is safe for humans and the environment, and before regulatory standards exist, companies can be exposed to significant financial, legal, and reputational risk. The limited studies that exist on nanomaterials, including nanoscale titanium dioxide*, have indicated that ingestion of these particles may pose health hazards.

The inaction of regulators does not protect companies, especially when the regulators themselves warn of the dangers of nanoparticles’ largely unknown risks. Draft guidance issued by the U.S. Food and Drug Administration raises questions about the safety of nanoparticles and demonstrates the general lack of knowledge about the technology and its effects. (1)

Asbestos litigation is a good example of the risks that can arise from using an emerging technology before it is proven safe. Use of asbestos (a nanomaterial) has created the longest, most expensive mass tort in national history with total U.S. costs now standing at over $250 billion. (2) If companies been asked to investigate and minimize or avoid risks prior to adopting asbestos technology, a sad and expensive chapter in worker harm could have been avoided.

* Titanium dioxide is a common pigment and FDA-approved food additive. It is used as a whitener, a dispersant, and a thickener.

While I don’t particularly appreciate fear-mongering as a tactic, the strategy of targeting investors and their concerns, seems to have helped As You Sow win its way.

US Food and Drug Administration approval for next generation spinal interbody fusion implant

For the first time, the US Food and Drug Administration (FDA) has approved a nanotechnology-enabled interbody spinal fusion implant, according to a Nov. 12, 2014 news item on Azonano,

Titan Spine, a medical device surface technology company focused on developing innovative spinal interbody fusion implants, today announced that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market its Endoskeleton® line of interbody fusion implants featuring its next-generation nanoLOCKTM surface technology.

This clearance marks Titan’s line of Endoskeleton® spinal implants as the first FDA-approved interbody fusion devices to feature nanotechnology.

A Nov. 22, 2014 news item on Today’s Medical Developments.com provides more detail about the implants,

Titan’s new nanoLOCK surface technology enhances the company’s line of Endoskeleton devices with an increased amount of nano-scaled textures to up-regulate a statistically significant greater amount of the osteogenic and angiogenic growth factors that are critical for bone growth and fusion when compared to PEEK and the company’s current surface.

Barbara Boyan, Ph.D., dean of the School of Engineering at Virginia Commonwealth University, and an investigator in various Titan Spine studies, said, “This new surface technology further enhances Titan’s current surface and is the result of extensive research in how to create a significantly greater amount of nano-scaled textures that we have shown to be important for the osteogenic response necessary for fusion. The nanoLOCK surface topography is far different than what is found on titanium-coated PEEK implants. In addition, the nanoLOCK surface is not created by applying a coating, but rather is formed by a reductive process of the titanium itself. This eliminates the potential for delamination, which is a concern for products with a PEEK-titanium interface. My team is proud to collaborate with Titan Spine to help develop such a differentiated technology that is truly designed to benefit both patients and surgeons.”

Titan’s nanoLOCK surface is a significant advancement of the company’s first-generation surface. The patented nanoLOCK manufacturing process creates additional textures at the critical nano level. However, there are no changes to the device indications for use, design, dimensions, or materials. Additionally, mechanical testing demonstrated that the strength of the company’s line of Endoskeletonimplants are unaffected by the new surface treatment.

Earlier this year Titan Spine announced the first surgery using one of its Endoskeleton implants. From a July 14, 2014 Titan Spine press release,

Titan Spine, a medical device surface technology company focused on developing innovative spinal interbody fusion implants, today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) to commercially release its Endoskeleton® TL system, a spinal fusion system utilizing a lateral approach. The Endoskeleton® TL represents the first lateral fusion device to feature surface technology that is designed to participate in the fusion process by creating an osteogenic response to the implant’s topography.

The Endoskeleton® TL device utilizes Titan’s proprietary roughened titanium surface technology which has been shown to upregulate the production of osteogenic and angiogenic factors that are critical for bone growth and fusion. In addition, the design of the TL device incorporates large windows and large internal volumes to allow for significant bone graft packing, clear CT and MRI imaging, desired bone graft loading, and the ability to pack additional bone graft material within the device following implantation. Members of the TL design team include Kade Huntsman, M.D., Orthopedic Spine Surgeon with the Salt Lake Orthopaedic Clinic in Salt Lake City, Utah; Andy Kranenburg, M.D., Co-Medical Director of the Providence Medford Medical Center Spine Institute in Medford, OR; Axel Reinhardt, M.D., Head of the Department of Spinal Surgery at the Specialized Orthopaedic Hospital in Potsdam, Germany; and Paul Slosar, M.D., Chief Medical Officer for Titan Spine.

Dr. Huntsman performed the first surgeries utilizing the Endoskeleton® TL on July 9th, 2014 at St. Mark’s Hospital in Salt Lake City, Utah. …

“The Endoskeleton® TL device is the first application of surface technology to the lateral approach,” commented Dr. Slosar. “The ability to orchestrate cellular behavior and promote bone growth in response to an interbody device has not been in the lateral surgeon’s armamentarium until now. The TL is the byproduct of a unique collaboration between academic biomaterial scientists, spine surgeons, and industry experts to create a truly differentiated lateral interbody device that is designed to benefit both patients and surgeons. With the addition of the TL device, Titan Spine now offers its surface technology and complete line of titanium devices for virtually all interbody fusion spine surgery procedures in the cervical and lumbar spine.”

The full line of Endoskeleton® devices features Titan Spine’s proprietary implant surface technology, consisting of a unique combination of roughened topographies at the macro, micro, and cellular levels. [emphasis mine] This combination of surface topographies is designed to create an optimal host-bone response and actively participate in the fusion process by promoting new bone growth, encouraging natural production of bone morphogenetic proteins (BMP’s) and creating the potential for a faster and more robust fusion.

It would seem the implant used in the July 2014 surgery is not nanotechnology-enabled, which suggests nanoLOCK is a next-generation implant being marketed only a few months after the first generation was made available. Unfortunately, the Titan Spine website is still partially (‘surface technology’ tab) under construction so I was not able to find more details about the technology. In any event, that’s quite a development pace.

Treatment for patients infected with the ebola virus (a response to crisis in West African countries)

I’ve not actively kept up with the situation in the West African countries suffering an outbreak of the ebola virus other than to note that it is ongoing. My Aug. 15, 2014 post provides a snapshot of the situation and various new treatments, including one based on tobacco, which could be helpful but appeared not to have been tested and/or deployed. There was a lot of secrecy (especially from Medicago, a Canadian company) regarding the whole matter of treatments and vaccines.

There seem to have been some new developments on the treatment side, involving yet another Canadian company, Tekmira, according to a Sept. 23, 2013 news item on Azonano,

Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, today announced that the FDA [US Food and Drug Administration] has authorized Tekmira to provide TKM-Ebola for treatment under expanded access protocols to subjects with confirmed or suspected Ebola virus infections.

A Sept. 22, 2014 Tekmira news release, which originated the news item, expands on the topic of regulatory issues associated with bringing this treatment to the areas suffering the outbreak,

“Tekmira is reporting that an appropriate regulatory and clinical framework is now in place to allow the use of TKM-Ebola in patients. We have worked with the FDA and Health Canada to establish this framework and a treatment protocol allowing us to do what we can to help these patients,” said Dr. Mark J. Murray Tekmira’s President and CEO.

“We have insisted on acting responsibly in the interest of patients and our stakeholders,” added Dr. Murray. “Today we are reporting that, working closely with regulators in the United States and Canada, we have established a framework for TKM-Ebola use in multiple patients. In the US, the FDA has granted expanded access use of TKM-Ebola under our Investigational New Drug application (IND) and Health Canada has established a similar framework, both of which allow the use of our investigational therapeutic in more patients.”

“We have already responded to requests for the use of our investigational agent in several patients under emergency protocols, in an effort to help these patients, a goal we share with the FDA and Health Canada. TKM-Ebola has been administered to a number of patients and the repeat infusions have been well tolerated. However, it must be kept in mind that any uses of the product under expanded access, does not constitute controlled clinical trials. These patients may be infected with a strain of Ebola virus which has emerged subsequent to the strain that our product is directed against, and physicians treating these patients may use more than one therapeutic intervention in an effort to achieve the best outcome,” said Dr. Murray. “Our TKM-Ebola drug supplies are limited, but we will continue to help where we can, as we continue to focus on the other important objectives we have to advance therapies to meet the unmet needs of patients.”

TKM-Ebola is an investigational therapeutic, being developed under an FDA approved IND, which is currently the subject of a partial clinical hold under which the FDA has allowed the potential use of TKM-Ebola in individuals with a confirmed or suspected Ebola virus infection.

About FDA Expanded Access Program

Expanded access is the use of an investigational drug outside of a clinical trial to treat a patient, with a serious or immediately life-threatening disease or condition, who has no comparable or satisfactory alternative treatment options. FDA regulations allow access to investigational drugs for treatment purposes on a case-by-case basis for an individual patient, or for intermediate-size groups of patients with similar treatment needs who otherwise do not qualify to participate in a clinical trial. (Source: www.fda.com)

About TKM-Ebola, an Anti-Ebola Virus RNAi Therapeutic

TKM-Ebola, an anti-Ebola virus RNAi therapeutic, is being developed under a $140 million contract with the U.S. Department of Defense’s Medical Countermeasure Systems BioDefense Therapeutics (MCS-BDTX) Joint Product Management Office. Earlier preclinical studies were published in the medical journal The Lancet and demonstrated that when siRNA targeting the Ebola virus and delivered by Tekmira’s LNP [Lipid Nanoparticle] technology were used to treat previously infected non-human primates, the result was 100 percent protection from an otherwise lethal dose of Zaire Ebola virus (Geisbert et al., The Lancet, Vol. 375, May 29, 2010). In March 2014, Tekmira was granted a Fast Track designation from the U.S. Food and Drug Administration for the development of TKM-Ebola.

About Joint Project Manager Medical Countermeasure Systems (JPM-MCS)

This work is being conducted under contract with the U.S. Department of Defense Joint Project Manager Medical Countermeasure Systems (JPM-MCS). JPM-MCS, a component of the Joint Program Executive Office for Chemical and Biological Defense, aims to provide U.S. military forces and the nation with safe, effective, and innovative medical solutions to counter chemical, biological, radiological, and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance biodefense response capability. For more information, visit www.jpeocbd.osd.mil.

About Tekmira

Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle (LNP) delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Further information about Tekmira can be found at www.tekmira.com. Tekmira is based in Vancouver, B.C. Canada.

Forward-Looking Statements and Information

This news release contains “forward-looking statements” or “forward-looking information” within the meaning of applicable securities laws (collectively, “forward-looking statements”). Forward-looking statements in this news release include statements about Tekmira’s strategy, future operations, clinical trials, prospects and the plans of management; an appropriate regulatory and clinical  framework for emergency use of TKM-Ebola in subjects with confirmed or suspected Ebola infections; FDA grant of expanded access use of TKM-Ebola under Tekmira’s IND; Health Canada’s establishment of a similar framework for TKM-Ebola; Tekmira’s response to requests for the use of TKM-Ebola in several patients under emergency protocols and the results thereon; the current supply of TKM-Ebola drug; the partial clinical hold on the TKM-Ebola IND by the FDA (enabling the potential use of TKM-Ebola in individuals with a confirmed or suspected Ebola virus infection); the quantum value of the contract with the JPM-MCS; and Fast Track designation from the FDA for the development of TKM-Ebola.

With respect to the forward-looking statements contained in this news release, Tekmira has made numerous assumptions regarding, among other things, the clinical framework for emergency use of TKM-Ebola. While Tekmira considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies.

Additionally, there are known and unknown risk factors which could cause Tekmira’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: TKM-Ebola may not prove to be effective in the treatment of Ebola infection under the emergency use framework, or at all; any uses of TKM-Ebola under emergency INDs are not controlled trails, and TKM-Ebola may be used on Ebola strains that have diverged from the strain to which TKM-Ebola is directed, and physicians treating patients may use more than one therapeutic intervention in addition to TKM-Ebola; the current supply of TKM-Ebola is limited, and Tekmira may not be able to respond to future requests for help in the current Ebola outbreak; the FDA may not remove the partial clinical hold on the TKM-Ebola IND; the FDA may refuse to approve Tekmira’s products, or place restrictions on Tekmira’s ability to commercialize its products; anticipated pre-clinical and clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested drug candidate; and Tekmira may not receive the necessary regulatory approvals for the clinical development of Tekmira’s products.

A more complete discussion of the risks and uncertainties facing Tekmira appears in Tekmira’s Annual Report on Form 10-K and Tekmira’s continuous disclosure filings, which are available at www.sedar.com or www.sec.gov. All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Tekmira disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law.

In the midst of all those ‘cover your rear end’ statements to investors, it’s easy to miss the fact that people are actually being treated and the results are promising, if not guaranteed,

Tekmira has distributed a Sept. 23, 2014 news release touting its membership in a new consortium, which suggests that in parallel with offering treatment, human clinical trials will  also be conducted,

Tekmira Pharmaceuticals Corporation (Nasdaq:TKMR) (TSX:TKM), a leading developer of RNA interference (RNAi) therapeutics, today reported that it is collaborating with an international consortium to provide an RNAi based investigational therapeutic for expedited clinical studies in West Africa.

Led by Dr. Peter Horby of the Centre for Tropical Medicine and Global Health at the University of Oxford and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), the consortium includes representatives from the World Health Organization (WHO), US Centers for Disease Control, Médecins Sans Frontières – Doctors without Borders (MSF), ISARIC, and Fondation Mérieux, among others.

The Wellcome Trust has announced it has awarded £3.2 million to the consortium to fund this initiative. The award will include funds for the manufacture of investigational therapeutics as well as the establishment of an operational clinical trials platform in two or more Ebola Virus Disease (EVD) treatment centers in West Africa. RNAi has been prioritized as an investigational therapeutic and may be selected for clinical trials at these centers.

The objective of the clinical trials is to assess the efficacy and safety of promising therapeutics and vaccines, reliably and safely, in patients with EVD by adopting strict protocols that comply with international standards.  It is hoped this initiative will permit the adoption of safe and effective interventions rapidly.

The genetic sequence of the Ebola virus variant responsible for the ongoing outbreak in West Africa is now available. Under this program, Tekmira will produce an RNAi based product specifically targeting the viral variant responsible for this outbreak.  The ability to rapidly and accurately match the evolving genetic sequences of emerging infectious agents is one of the powerful features of RNAi therapeutics.

“We commend the Wellcome Trust for their leadership in providing the necessary funds to launch and expedite this ground breaking initiative. We are gratified that RNAi has been prioritized as a potential investigational therapeutic to assist in the ongoing public health and humanitarian crisis in Africa,” said Dr. Murray, Tekmira’s President and CEO.

“We are an active collaborator in this consortium and through our ongoing dialogue with the WHO, NGOs and governments in various countries; we have been discussing the creation of appropriate clinical and regulatory frameworks for the potential use of investigational therapeutics in Africa. This initiative goes a long way towards achieving this aim.  Many complex decisions remain to fully implement this unique clinical trial platform.  At this time, there can be no assurances that our product will be selected by the consortium for clinical trials in Africa,” said Dr. Murray.

About Wellcome Trust

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. For more information, visit www.wellcome.ac.uk

I’m glad they’re being careful while giving people treatment, i. e., trying to do something rather than waiting to conduct human clinical trials as has sometimes been the case in the past. This business of running the trials almost parallel to offering treatment suggests an agility not often associated with the international health care community.

ETA Sept. 23 2014 1200 hours PDT: For more information about the status of the Ebola outbreak read Tara Smith’s Sept. 22, 2014 article Slate titled, Here’s Where We Stand With Ebola; Even experienced international disaster responders are shocked at how bad it’s gotten (Note: Links have been removed).

Now, terms like “exponential spread” are being thrown around as the epidemic continues to expand more and more rapidly. Just last week, an increase of 700 new cases was reported, and the case count is now doubling in size approximately every three weeks.

A Doctors Without Borders worker in Monrovia, Liberia, named Jackson Naimah describes the situation in his home country, noting that patients are literally dying at the front door of his treatment center because it lacks patient beds and assistance; the sufferers are left to die a “horrible, undignified death” and potentially infect others as they do so: …

… Health care workers who are treating the sick are dying because they also lack basic protective equipment, or because they have been so overwhelmed by taking care of the ill and dying that they begin to make potentially fatal errors. They have gone on strike in Liberia because they are not being adequately protected or even paid for their risky service.

Fear and misinformation are as deadly as the virus itself. Eight Ebola workers were recently murdered in Guinea, in the area where the virus first came to the world’s attention in March. Liberia’s largest newspaper featured a story describing Ebola as a man-made virus being purposely unleashed upon Africans by Western pharmaceutical companies. Reports abound of doctors and other workers being chased away, sometimes violently, by fearful families. …

It’s not a pleasant read but, I think, a necessary one. For anyone who may think the panic and fear are unique to this situation, I once worked with a nurse who described being lifted by her neck after someone came through the door of a clinic demanding a vaccine and had been refused. He was in such a panic and so fearful he wasn’t going to take a ‘no’. The incident took place in Vancouver (Canada) in a ‘nice’ part of town.

ETA Sept. 24, 2014: Kelly Grant has written a Sept. 22, 2014 article for the Globe and Mail which provides more information about Tekmira, some of which contradicts the details I have here about TKM-Ebola and clinical trials in Africa although the key points remain the same. She also provides more information about the ZMapp therapy (mentioned in my Aug. 15, 2014 post) noting yet a third Canadian connection.* Canada’s National Microbiology Laboratory was somehow involved in developing ZMApp, unfortunately, Grant does not or is not able to provide more details about that involvement.

ETA Oct. 16, 2014: David Bruggeman recommends a digital journalism site Ebola Deeply for some in depth reporting in his Oct. 16, 2014 posting.

* This sentence “She also provides more information about the ZMapp therapy mentioned in my Aug. 15, 2014 post mentioning yet a third Canadian connection.” was altered for grammatical purposes on Dec. 4, 2014.

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.