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The meeting came to order at 9:00 a.m. in the Natcher Auditorium, Building 45 of the National Institutes of Health, Bethesda, MD. Dr. Norris Alderson and Dr. Randy Lutter, co-chairmen, presiding.
NORRIS ALDERSON, CO-CHAIRMAN
RANDY LUTTER, CO-CHAIRMAN
Welcome
National/Regional Perspective
Dr. Celia Merzbacher
Dr. Philippe Martin
Dr. Delara Karkan
Session 1:
John Balbus
David Berube
Carolyn Cairns
Kenneth David
Stacey Harper
Matthew Jaffe
Session 2:
Martin Philbert
Dave Rejeski
Michael Taylor
Bruce Levinson
Kathy Jo Wetter
Session 3:
Pascal Delrieu
Jane Houlihan
George Kimbrell
Erich Pica
Michael Roberts
Annette Santamaria
Session 4:
Phillip Buckler
Neil Desai
Anil Diwan
Piotr Grodzinski
Session 5:
Deborah Ledenheim
Bernie Liebler
Scott McNeil
Session 6:
Lutz End
9:04 a.m.
CHAIRMAN LUTTER: Ladies and gentlemen, good morning. I'd like to welcome you to this public meeting on nanotechnology. I'm Randall Lutter, Co-Chair of FDA's Nanotechnology Task Force and my Co-Chair, Dr. Norris Alderson and I are delighted to have the honor of chairing this meeting today.
The presence of all of you suggests that we'll benefit from a large number of comments about nanotechnology and FDA-regulated products and today we're looking forward to an informative and wide-ranging discussion. I'd like to sketch briefly FDA's efforts to protect and promote public health in a world where nanotechnology is no longer a topic only for basic research, then I'll lay out some procedural points for our meeting today and after that, we'll begin the different sessions.
By way of scientific background, nanotechnology materials often have chemical or physical properties that are different from those of their larger counterparts because of their small size and extremely high ratio of surface area to volume. Such differences include altered magnetic properties, altered electrical or optical activity, increased structural integrity and increased chemical and biological activity. Because of these properties, nanotechnology materials have great potential for use in a vast variety of products. Also because of some of their special properties, they may pose different safety issues than their larger counterparts.
Of particular interest to FDA, nanotechnology materials may enable new developments in implants and prosthetics, drug delivery and food processing and may already be in use in some cosmetics and sun screens. FDA also is interested in learning if there are opportunities for it to help overcome scientific hurdles that may be inhibiting the use of nanotechnology in medical product development. FDA generally is responsible for overseeing the safety and effectiveness of drugs for humans and animals, biologics and medical devices for humans and the safety of foods including dietary supplements, food and color additives, cosmetics and animal feeds.
It does so under a variety of laws and regulations and depending on product class under a variety of pre-market and post-market mechanisms. While most, if not all, of the key laws and regulations under which FDA operates were written before the advent of nanotechnology, most are general in nature by design. They, therefore, usually are able to accommodate products made with the use of new technologies or containing new kinds of materials. At this time, we're not aware of any adverse safety issues associated with the use of nanotechnology-based materials in FDA regulated products.
In fact, for some cancer drugs under development, the opposite may be true, with better targeting and lower doses of toxic drugs needed through use of nanotechnology delivery methods. Nanotechnology is also offering advances in things like lab on a chip, clinical diagnostic testing and I'm told that nanotechnology materials may soon greatly enhance our ability to see inside the body using MRI or other non-invasive techniques that would reduce the need for exploratory surgery.
As noted below, we're evaluating the effectiveness of the agency's regulatory approaches and authorities to meet any unique challenges that may be presented by the use of nanotechnology materials in FDA-regulated products. We look forward to gathering more information today and through submissions to the docket for this meeting to assist our evaluation, including information on safety considerations for use of nanotechnology materials in FDA-regulated products. Because of the generality of laws and regulations, FDA often finds it useful to develop guidance documents tailored to specific issues posed by new kinds of products or processes. Such guidance documents, while not binding on industry or the agency, can illustrate how the agency interprets existing law and regulation with respect to new products or processes. It may also describe the kinds of information FDA considers appropriate to demonstrate the safety or effectiveness of products made with new kinds of materials or processes or describe new procedures for interacting with the agency to help facilitate the safe entry into the marketplace of new products.
We've not yet developed guidance for products using nanotechnology materials but part of the work of FDA's task force on nanotechnology is to evaluate whether such guidance might be useful for particular product areas. We're holding this meeting today because we're interesting in learning about the kinds of new nanotechnology material products under development in areas of food, including dietary supplements, food and color additives, animal feeds, cosmetics, drugs and biologics and medical devices. We're also interested in learning whether there are new or emerging scientific issues that should be brought to FDA's attention, including issues related to safety of nanotechnology materials.
Finally, we're interested in any other issues about which the regulated industry, academia, and the interested public may wish to inform us concerning the use of nanotechnology materials in FDA- regulated products. This meeting also helps us comply with tasks assigned to the FDA's nanotechnology task force which I will introduce shortly by Acting Commissioner Dr. Von Eschenbach on August 9th. Those tasks are as follows; first, assess the current state of scientific knowledge pertaining to nanotechnology materials for purposes of carrying out FDA's mission; second, evaluate the effectiveness of the agency's regulatory approaches and authorities to meet any unique challenge that may be presented by the use of nanotechnology materials in FDA-regulated products and; third, explore opportunities to foster innovation using nanotechnology materials to develop safe and effective drugs, biologics and medical devices and to develop safe foods, feeds and cosmetics; fourth, continue to strengthen FDA's collaborative relationships with other federal agencies, including the agencies participating in the National Nanotechnology Initiative, such as the National Institutes of Health, the Environmental Protection Agency, and the US Department of Agriculture, as well as with foreign government regulatory bodies, international organizations, and private parties.
Fifth, consider appropriate vehicles for communicating with the public about the use of nanotechnology materials in FDA regulated products and finally, Dr. Von Eschenbach asked us to submit the initial findings and recommendations to him within nine months of this public meeting. So there will be a public report. Clearly, today's meeting is a key part of FDA's ongoing efforts to gather and evaluate information relating to the use of nanotechnology in the manufacture of FDA-regulated products.
While products made using nanotechnology like those made using any new technology, may pose risks, FDA recognizes that nanotechnology has great potential to promote public health through advances in medical products, including in implants and prosthetics and other FDA-regulated products.
Let me turn now to some procedural points. The meeting today is divided into three distinct parts. Immediately following my remarks will be presentations by three government officials representing the US Office of Science and Technology Policy, of the European Commission and Health Canada. Subsequently, at 10:00 a.m. and ending this afternoon at 4:25 there will be six different sessions of presentations by public speakers who signed up in advance to speak at this meeting. If you haven't already checked in today, please do so at the table in the hall.
I realize the mike is now louder than it used to be. I hope everybody's been hearing me throughout my remarks. Would anybody like me to start again at the beginning? After your -- at the end of each session, members of FDA's task force may pose questions to speakers, at the end of each of these sessions, where needed as clarification for their statement. So there will be an opportunity for task force members to ask questions and the speakers to provide answers. We plan to post to our website any written or electronic materials used by speakers in the next week or so and recognizing that the speakers have limited time for their talks, we encourage you to provide more extensive comments and information in submissions to the docket.
In particular, we would appreciate submission of any published or unpublished studies that you cite in support of your statements. And if you're unable to provide copies now, we'd appreciate any available abstracts and would encourage you to send the full studies as soon as they can be made publicly available.
The third part of our public meeting today is that at 4:25, we will have an open microphone session for additional speakers. Because of scheduling constraints, only the first 25 people who sign up for this period may speak. People may continue to sign up until 11:15 at the end of the last break before lunch unless 25 people have already signed up before that time. This way we can announce immediately before lunch the time available for each of these speakers, so they may use lunch to adjust their remarks to fit the available time. These speakers will speak in the order they sign up.
Of course, we ask all speakers to limit their remarks to exactly the allotted time. Dr. Alderson and I aim to stick to the schedule today. The number of people seeking lunch at noon will likely outstrip the capacity of the local cafeteria to serve everyone in the available time. We sent out via e-mail some maps to local restaurants. I think there are maps outside this auditorium describing how to find some restaurants other than the cafeteria within the building.
Finally, any member of the public who doesn't receive an opportunity to speak today or who would like more time than is available given today's filled schedule, is more than welcome to submit written comments to the public docket at our website. Written or electronic comments may be submitted by November 10th. Note that the submitted comments will be available to the public, so please do not include confidential business information. I'd like to now introduce the members of the task force, who are sitting the front rows facing the stage. Please stand as I call your name; Dr. Rick Canaday, Dr. Mitchell Cheeseman, Matt Eckel, I think is absent, Eric Flamm, Dr. Flammang is absent, Dr. Steve Fleischer, Dr. Paul Howard, from the National Center for Toxicological Research, Dr. Linda Katz, from the Center for Foods and Safety in Applied Nutrition, David Kelly from the Office of the Commissioner, Mark Kramer, from the Office of the Commissioner, I think, is absent, Pat Kuntze from the Office of the Commissioner, Dr. Subhas Malghan from the Center for Devices and Radiological Health, Dr. Nakissa Sadrieh from Center for Drug Evaluation and Research, Dr. Jeff Shuren, Dr. Jan Simak from the Center for Biologics Evaluation Research, Dr. Steve Vaughn from the Center for Veterinary Medicine, John Weiner, Office of Chief Counsel, Helen Winkle, Center for Drug Evaluation and Research. And we hope that everyone today will provide us with information that will increase our awareness of both the challenges and the opportunities that nanotechnology may provide and how we can best meet those challenges and opportunities. And without further ado, Dr. Norris Alderson will start our first session. Thank you very much. Look forward to enjoying discussions today.
CHAIRMAN ALDERSON: Well, good morning again. I'm Norris Alderson, if you hadn't figured that out. And we are delighted that you're here today and the next three speakers, as Randy indicated is to indicate both the national and regional perspectives on nanotechnology because it is truly that issue across all of the governments in the world and we are all working together in many ways.
And we're going to start today with the US perspective by Dr. Celia Merzbacher. Celia is currently on assignment to the Office of Science and Technology Policy, OSTP, and Executive Office of the President of the US Naval Research Laboratory. In her position at OSTP she is acting assistant director for technology research and development and handles issues related to nanotechnology and the National Nanotechnology Initiative. She also co-chairs the inter-agency Nanoscale Science, Engineering and Technology, NSET, Subcommittee of the National Science and Technology Council's Committee on Technology.
As part of her responsibilities at OSTP, she serves as Executive Director of the President's Council of Advisors on Science and Technology. That's PCAST. As an advisory body to the President, PCAST is a national nanotechnology advisory panel called for by the 21st Century Nanotechnology Research and Development Act of 2003. This body provides periodic assessments and recommendations for strengthening the Federal Nanotechnology Program. Celia.
DR. MERZBACHER: Good morning. Thank you all for coming out on a nice fall day. As Norris and Randy indicated, I'm here to talk about the US National Nanotechnology Initiative. I want to thank both of them for inviting me to speak. I hope you can hear me. This seems a very receptive microphone. And I want to thank the FDA for organizing today's meeting.
Although the purpose of the meeting is to help the FDA further its understanding of developments in nanotechnology materials that pertain to FDA- regulated products, it will, in fact, inform all of the agencies that participate in the National Nanotechnology Initiative, so I want to thank the speakers for participating as well, because those of us who are from other agencies and organizations are interested in hearing what you have to say.
What I'd like to talk about today is the Environmental Health and Safety or EHS research under the National Nanotechnology Initiative and how that's being coordinated and managed. And I just thought I would sort of put right on my first slide the four points that I want to make so that you'll get those up front and if nothing else, I hope you'll take these away from my presentation.
The first is that nanotechnology EHS research is a priority. And in fact, nanotechnology or NNI agencies are already doing a considerable amount of research in this area and the investment that's being made is in fact growing. And finally the inter-agency coordination process, I will, I hope convince you, guides the agencies that are part of the NNI. It effectively leverages the investment by each of the agencies across the entire government and going forward, it should, I think ensure that we avoid gaps in this area of research.
So starting with the first point, let's see, which -- in fact, nanotechnology is one of just a handful of priority areas of research that's called out in a document that's sent out each year. This is the top of the memorandum sent by the Directors of the Office of Science and Technology policy, Dr. Marburger and the Director of OMB, Mr. Portman. This is an annual research and development budget priorities memo that's sent to the heads of the departments and agencies indicating what the Administration's priorities are for the coming budget cycle.
And so this is the budget that was sent out as part of the planning for the fiscal year 2008 budget and if you scroll down, to the section on nanotechnology, it reads as follows, "To ensure that nanoscience research leads to the responsible development of beneficial applications, high priority should be given to research on societal implications, human health and environmental issues related to nanotechnology". It goes on to say, "Agencies should develop, where applicable, cross-agency approaches to the funding and execution of this research".
Now, in fact, this guidance from the Administration is completely aligned with the goals and priorities of the National Nanotechnology Initiative. In the strategic plan of the NNI which was released in 2004, the plan calls out four high level goals and the fourth of these goals is to support responsible development of nanotechnology. And the plan goes on -- the report that spells out the plan goes on to say that responsible development includes addressing potential risks to human health and the environment of new nanomaterials and the products that they are incorporated in.
Well, activities and investments aimed at achieving these goals are reported each year in an annual budget supplement that's sent to Congress and is publicly available, and all of these reports of NNI are available if you go to www.nano.gov. So this table is taken from the most recent annual budget supplement and we report each year now, the amount that's being spent by each of the agencies participating in the NNI on EHS research. So this table shows, and probably the people in the back can't see it, but it shows for all of the participating agencies that fund nanotechnology research the investment in EHS research in 2005, the amount that's being spent this year, 2006, and the amount that's being requested for 2007. And for the purposes of making these estimates, the definition of EHS research is research that is, and I'm quoting here, "primarily aimed at understanding and addressing potential risks to health and to the environment posed by nanotechnology". Now, I think if you just take a look at this, even if you can't read the numbers, you'll see that EHS research is in fact, being performed by a number of different agencies across the government and I sort of have made the bottom line bigger so that hopefully you can see it, the total NNI investment has been steadily growing. It was just under 34 million in 2005 and the plan is to spend just over 44 million in 2007. I want to reiterate that these estimates do not include research whose primary goals are not risk-related but that may, in fact, advance understanding and the ability to measure and characterize risks associated with nanomaterials. So it's really a low estimate, if you will.
The budget supplement also provides highlights of the current and planned activities in all areas of research, including EHS. So I encourage you to go to the nano.gov website if you haven't already read this and take a look at it. Actually let me stay with that slide for a moment. The inter-agency group that I co-chair felt that, in fact, greater coordination was going to be needed for EHS research and in 2003 it established the NEHI, Nanotechnology, Environmental and Health Implications working group. Norris Alderson is the chair of that group and its membership includes representatives from both the research agencies and the regulatory agencies.
A purpose of that group is to facilitate the identification, prioritization and implementation of the research required for the responsible development and oversight of nanotechnology. It has served as an invaluable forum for discussion and exchanging information about EHS issues related to nanotechnology and I don't think I've overstating it when I say that it has been unique, I think, among interagency activities in addressing EHS issues at such an early stage of development of an emerging technology.
So more recently the NEHI working group prepared and the National Science and Technology Council released a report entitled "Environmental Health and Safety Research Needs for Engineered Nanoscale Materials", a fairly self-explanatory title, I think. This report which just came out last month, identifies five broad areas for research and those are shown here, I won't read them to you. And these are the research -- these describe the research that's needed in order to support federal government risk assessment and risk management activities. For each area, the report describes selected current NNI research, detailed research needs within the area, and options for research approaches to address those needs.
The purpose of the report is primarily from our point of view, to serve the federal agencies. It identifies research and information that's needed for the regulatory agencies to be able to assess and manage risks and it also will inform and guide the research agencies as they plan their programs and budgets. But it's not really a government-specific document and we hope that industry may find it useful, in particular users and producers of nanomaterials may find it useful and informative for their own EHS activities and another audience is the nanomaterials and EHS research community which we hope will read it and be stimulated to submit proposals to the research agency solicitations that address the topics that are identified in this report.
Well, this is just a step, albeit an important step in identifying the research that's needed and the report goes on to say what the NEHI working group will do next. There's a need initially to further prioritize the research. This is a very broad compendium of the research that's needed and the report includes principles by which the agencies are going to do that prioritization. We also need to evaluate in greater detail what we're doing now and then do a gap analysis to see here those gaps exist and then take steps to coordinate with the agencies that invest in research to address any remaining gaps.
And finally, this is a very fast-moving area. And the NEHI feels it's important to establish a process by which we first of all, assess how much progress we're making towards addressing the research that's needed, and also to update this document periodically. Well, so far I've just been talking really about the NNI and what's going on among the federal agencies, but in fact, there are many others who are doing research in the area of nanotechnology EHS.
First of all, industry and in particular manufacturers of nanomaterials are doing their own EHS research, of course. Many of those data are proprietary. I just want to note that the Environmental Protection Agency has announced a public meeting on risk management practices within the scope of a possible stewardship program that the EPA is exploring. That's scheduled for October 19th and 20th here in Washington, DC and you can find more from the EPA website.
There are also non-profit research organizations that are spending money on nanotechnology EHS research and examples are the International Council on Nanotechnology and the International Life Sciences Institutes, Health and Environmental Science Institute. These organizations, perhaps, aren't spending as much as some of the other groups but I think they represent an important interface between many of the stakeholders, government and industry for example, and so they have an important role. And next, there are, of course, other governments that are spending money in this area and we're going to hear from representatives from the European Commission and Canada today, but many other nations are spending money in this area as well, which begs the question, we don't only need to coordinate perhaps, among the agencies of the government, but also with others around the world who are working in this areas and how might we go about doing that.
I'd like to just touch upon two international organizations that I think are going to be important and in fact, I think I'm safe in saying that every international organization that has a scientific or technological mandate is probably looking at how nanotechnology is going to impact its program of work. But two that I want to mention today are the Organization for Economic Cooperation and Development or OECD, which has established a new working party on manufacturing nanomaterials and that group is going to meet for the first time at the end of the month in London, and the International Organization for Standardization or ISO, which has created a technical committee on nanotechnologies to develop standards for nanotechnologies. They are focusing initially on three areas of standardization, terminology and nomenclature, instrumentation and metrology and health, safety and the environment. And in fact, I would argue that standards in all three of these areas are going to be critical to the successful advancement and realization of the benefits of nanomaterials in a safe and responsible manner.
So I can't really emphasize enough the importance of standards in going forward with the safe development and regulation of nanotechnology. So to recapitulate what I said in the beginning, I hope I've convinced you that nanotechnology is a research -- EHS research is a priority of the Administration and of the NNI. We already are doing quite a bit in this area. The NNI agencies are investing and the amount that they're spending is growing year by year. And finally, inter-agency bodies don't set the budgets. That's done at that agency level; but the work of the inter-agency bodies through their coordinating activities, guide the agencies. They ensure efficient investment and leveraging across the agencies and especially, I think going forward, they help to ensure that gaps in research will be filled.
We really need to be smart about how we spend our limited resources. Some research needs to happen in sequence and spending more money won't accelerate the process particularly. If we can't characterize nanomaterials, then we don't know what we're testing. And researchers and business people alike are clamoring for standards. So again, I want to emphasize the importance in that area. There's much to be done and the NNI, in coordination and collaboration with others around the world, is taking steps to protect human health and the environment.
Well, I see I have just about one minute left, so I'll wrap up. In closing, I'll note that the response to this public meeting exceeded expectations, I think and although I had the honor of being the first speaker today, like you, I'm really here to listen. So in behalf of OSTP and the NNI, I want to welcome everyone and thank you for your attention.
(Applause)
CHAIRMAN ALDERSON: Thank you, Celia. For those of you who didn't notice, I really want to point out that FDA was not one of those agencies listed for funding. Please note that and I'll try to bring it up as many times today as possible.
Our next speaker is part of our commitment to regional aspects of nanotechnology and FDA is continuously seeking to cooperate with its international regulatory partners in addressing nanotechnology issues both bilaterally and through multinational efforts such as the Organizations for Economic Cooperation and Development and the International Organizations for Standardization and Celia had mentioned both of those. We appreciate that Health Canada and the European Commission were able to send representatives to present today their views on nanotechnology.
Representatives from Japan's Minister of Health, Labor and Welfare and the European Agency for the Evaluation of Medicinal Products have also joined us for today's meeting. Our first speaker is Dr. Philippe Martin and he's the principal administrator for risk assessment and nanotechnology policy development in coordination with the European Commission's Directorate for Health and Consumer Protection and that's part of DG SANCO. And DG SANCO works to insure that food and consumer goods sold in the European Union are safe and that its citizens' health is protected. Dr. Martin.
DR. MARTIN: Well, thank you, Norris, and thank you very much to -- on behalf of the European Commission to FDA for inviting us at what we believe is a very important meeting. You will immediately note from my slides we did not trade notes with Celia, that there's a lot of convergence of views in particular with respect to international cooperation. And the other aspect which -- on which everybody agrees is that safety is a prerequisite to the development of nanotechnologies. Finally, I very much look forward to listening to the public, to you today.
And to give you an idea of what I will briefly talk about, I'll say a few words about nanotechnologies, things that actually Randy has already mentioned and Celia in her talk. I'll say a few words about the European Action Plan on Nanoscience and Nanotechnologies which was adopted in 2005. Then I will mention international cooperation and I here immediately insist on the fact that it's not just governmental or inter-governmental cooperation but cooperation between all stakeholders. Then I have to say a word about corporate responsibility because industry has a major role to play in this area and finally, I'll conclude with steps forward.
So we have many benefits that were evoked and coming from the health and consumer protection area, I am especially interested in health and medicine but clearly there are many other areas, including information technology, energy production, storage and distribution, material sciences, clearly, food, water and the environment is another area and finally instrumentation, especially sensors which in this day and age are becoming very important.
Then, just to give you my summary of what I see as the defining characteristics and I will admit to a risk assessment bias, what I see as the characteristics of nanotechnologies. So small is small. Small is different and small is hard to predict. So small is small, what do I mean? I mean that this absolute size of a billionth of a meter is also small with respect to the natural barriers to the entry and the movement of particles in the human body, not that we have not been submitted to such nanoparticles before, but not the kind that our bodies have learned to accept and handle. In particular, I have to stress the crossing of cell membranes and the possible crossing given special coatings on the nanoparticles of the blood/brain barrier, which, as you will note, both present a risk and may be an opportunity in the treatment of disease.
Then to demonstrate that small is different and also show that public servants can have a sense of humor, I took the idea, the metaphor used in National Geographic. You take -- they said that nanotechnology was you take something -- you take a cat, you shrink it, you shrink again, you shrink it yet and it turns into a dog.
(Laughter)
And here it's no mistake that I chose an angry looking dog, because if I don't know which kind of dog I'm facing, I have to assume as somebody who protects public health and consumers, that it could be an angry dog. And then the other aspect is that small is hard to predict. And for instance, a number of people wear rings, like myself and we know that gold is yellow, melts at 1,200 degrees and is completely inert. It doesn't leave stain marks. Well, if you take a one nanometer particle of gold, it's blue. It has low reactivity and now melts at 200 degrees C. And if you take a three nanometer gold particle, it reddish, catalytic and melts at 200 degrees. Catalytic means that it triggers reaction and is itself, very reactive. And this is a property that is very difficult to predict. Basically, you have to run the test to know what is happening for several reasons.
One of them because of the equations that you would need to solve and second, because it's very expensive in terms of computer time. However, I have to say that there is hope that we may be able to use structure-function relationships and so-called QSARs in the future to help us.
Now, a few words about the European Action Plan; the message I want to deliver is that it seeks -- and that message was blessed by the 25 ministers of Europe, of the European member states, that Europe chooses a safe, integrated and responsible approach to the development of nanoscience and nanotechnologies. And what are we trying to achieve? Well, economic prosperity, social well-being and environmental quality. And if you're really interested in the action plan, you can use a search engine like Google to find more about it, but basically, it's got eight chapters.
One of them, probably the most important one in terms of direct funding is R&D which includes R&D on risk research. And we are presently finalizing what we in Europe call the Seventh Framework Program which is going to run from 2006 to 2013 and it includes very detailed research on safety and HSI aspects. The other chapters include clearly support to innovation, examining the societal aspects, the ethical aspects, and clearly risk assessment research as well as an international component.
Now, to do its policy, the European Commission relies on science as much as it can. It's policy is built on science. And to do that, it has actually three scientific committees that handle non-food areas. There's one that handles products, another one that handles the environment and one that handles emerging and newly identified risks in which we've placed nanotechnologies. But there are also other committees that help us in approving products. For drugs it's going to be European Medicines Evaluation Agency and for food, it's going to be the European Food Safety Authority.
The one aspect that I have to stress is that the EU is not one sovereign nation-state but actually a collection of 25 nation-states. Even though now everybody can vote where they live in county elections, that's as far as it goes and therefore, there is underlying those committees, very often a network of national committees that support the work as well.
The Scientific Committee on Emerging and Newly Identified Health Risks delivered an opinion on nanotechnologies looking at the appropriateness of existing risk assessment methods. And the conclusions were that risk assessment methods may require modification. It was not a blanket statement saying we've got nothing. No, we've got something but we have to be very careful, in particular because we cannot assume that what we know about the bulk substance applies to the nanosubstance or the substance in nano form, and therefore, we have to operate on a case by case basis.
Then it stressed -- it pointed out adaptations to the methods. Well, we need to examine the methodologies, the tests and the equipment because if you don't have the right equipment, you're not able to go anywhere. You will be blind to nanoparticles in particular. Knowledge gaps, and this has been the focus on both sides of the Atlantic and elsewhere of much effort recently and especially characterization mechanism and toxicokinetics are stressed as very important. But they're not the only aspect. As you well know, there is a risk only if you have both a hazard and exposure to the hazard. So measurements are needed on exposure because if, for instance, I consider the nanoelectronics in the computer here, they're sunk in a solitary state piece which means that I and you are not being exposed in any significant manner to whatever nano there is in this computer.
So that's one aspect and we need portable equipment to be able to monitor both human and environmental exposure and we need also to understand the severity of unknown - better of what happens in the environment, how do things move in the environment, how do they change, how do they accumulate, how do they degrade.
And now moving onto the more regulatory part of my talk, the EU has undertaken -- has started a legislative review and it is not -- there are no public documents yet on it and I'm actually accompanied -- we're both from the European Commission here today. I'm here with my colleague Case Brekelmans who oversees the writing, who's actually the pen behind this legislative review and we're both available for questions outside of this meeting if you wish.
But anyway, the main message is that the framework looks okay and that is a message that has been relayed at national level elsewhere. It has also been pointed out that there are some gaps and for instance, in its review of UK legislation, the Food Standards Agency has called out a series of local gaps in the regulation that can, should and will be handled. The other message is that the real priority is implementation. Maybe do we not need better regulation, maybe, but we certainly need better implementation. In support of this work, we're now having the committee that delivered the opinion on the methods applicable to risk assessment work on, as Celia mentioned, the technical guidance documents, basically those non-legal documents that make the application of the law possible.
And we're also working on - the Scientific Committee on Consumer Products which in particular considers authorization of cosmetics, is working on an opinion on nanomaterials in cosmetics and this work has started in February this year and obviously, it -- later developments in this area have shown that it was a very timely thing to examine. But I also would like to insist and that's where it's not only a matter of producing new research, it's also a matter of sharing data. Regulators need the data that is available today and there is data and for this we need really to partner with industry in the area of cosmetics for instance.
The committee really needs support from industry and confidential private information can be handled by those committees at least in the European system. Then international cooperation, the reason I put it between brackets is that it really is cooperation worldwide and this international business is actually -- is de facto. Everybody is talking to everybody. There are informal dialogues like the NSF sponsored international dialogues, like those initiatives, like the International Risk Governance Council. There are formal dialogues like the ones that are taking place at the OECD as mentioned by Celia as well as in ISO or UNESCO. And there is dialogue between stakeholders, between government and industry and representatives of the civil society and academia, obviously. Here I put the little thumbnails of the OECD, the ISO and the sandwich is the European equivalent of ISO.
A word about corporate responsibility; we feel in Europe that the catch-me-if-you-can paradigm is not appropriate for nanotechnologies. Rather, we applaud the efforts toward product stewardship like the ones that are being fostered by Dupont and Environmental Defense and here I've clearly, for those of you who know this -- the work of Dupont and Environmental Defense, I've really borrowed from them. I've added one step. The first step being for me very important, at the research stage to build in safety; the second stage to describe the material and its use, then analyze its life cycle, evaluate the risk, hazard, plus exposure, assess the risk management strategies and then clearly have a record. Decide what you want to decide but then document and act and periodically monitor and review so that you may adapt appropriately.
Before closing, I want to say a few words about the recent conference that was organized by the Finnish Presidency of the EU, for you to know every six months it's like Europe has a new government and one of the member states actually takes charge of the leadership. And that was a conference organized under this leadership. So the objective was to ensure the safe, integrated and responsible development of nanotechnologies. There were about 200 people, a very balanced representation of stakeholders from 20 countries including the USA and the conclusions were very straightforward. It's imperative to demonstrate safety and make it a standard. To advance R&D definition standards and instrumentation, regulation and data, to strengthen coordination and stakeholder dialogue and to produce a roadmap to know who does what, where and when.
In conclusion, I think everybody agrees nanotechnologies hold great promises. They do entail risk like those cadmium selenite quantum dots, that really are proof of concept but probably should not be used on humans. They could be used in vitro, maybe, or probably, and that this requires strengthening cooperation, advancing risk research, filling the data gaps with the data we have or by generating new data and setting international safety standards. Thank you very much.
(Applause)
CHAIRMAN ALDERSON: Thank you, Philippe. It's pleasing for me as Chair of NEHI which you talk about to see, many of the things that Philippe identified in his presentation are the same issues that NEHI's been talking about as related to risk assessment, particularly environmental and health risk. So in that respect, we are on the same page, if you will or our thinking is and that's always great to hear, but he also points out there's opportunities for cooperation that we must take advantage of.
Our next speaker is Dr. Delara Karkan. She's the Associate Director of the Center for Evaluation of Radiopharmaceuticals and the Biotherapeutics and the Biologics and Genetic Therapeutics Directorate at Health Canada. That's a mouthful. She has been with this directorate for two years. She is a clinical pharmacologist from the University of British Columbia, has worked as an Associate Director for Drug Development in publicly traded Canadian biotechnology companies and contract research organizations in the field of drug delivery and nanotechnology.
Previously, she worked at AstraZeneca and Glaxo Wellcome as a Research Fellow in drug development. She is also a visiting scientist at the National Research Council of Canada, working on nanotechnology, based imaging agents. Dr. Karkan.
DR. KARKAN: I want to thank you for inviting me. It's a pleasure to be here. And I want to thank the FDA team for a very well organized event. Having seen the slides and being the third speaker, I find my slides, some of them are a copy of the European Commission's slides and so I'm wondering now if the Office of Applied Technology actually copied some of your slides because they're identical. But I hope to find something new among my slides that would be of interest to the audience.
I'm going to actually, before that I'm going to give you an overview because I don't have a slide for an overview. I'm going to give you an overview of activities currently in Canada in the area of nanotechnology that's not only the Ministry of Health but other ministries and non-governmental organizations, what's happening in Canada and where we think we are heading to as well as some specific initiatives at Health Canada that may be of interest to you. And I'm going to start with some overview of nanotechnology again. I'll try not to repeat what was said before.
As we know and this is how we see it in Canada, that there is no official definition really for nanotechnology and it's generally described as the science and technology that creates, manipulates and manages material. Two specific features are the size and the property of these material. And that's what we're focusing on in terms of our research as well as in terms of setting up new regulations for these products. I'm again repeating here very briefly. The nanometer scale which is related to the size, a billionth of the meter, in Canada we're still using the old metric system, so, yes, a billionth of a meter, 1/80 thousand of human hair as well as one hundredths of the size of a virus and as my colleague on the European Commission said, half the diameter of a DNA double helix.
What we are dealing with in Canada in terms of products that have been submitted to us for review or products that are entering the market are both the fine particle products as well as the manufactured nanomaterial, and we find that they're different and dealing with them needs different set of skills, especially in terms of health assessment, risk assessment and toxicology. For example, I'm just going to give one example as the ability to find particles if you look at their chemical complexity, they're complex and they are less reactive but if you look at manufacturing nanomaterial and you're getting more and more -- and our research centers are producing more and more manufactured nanomaterial, and you see that they're chemically well-defined and they're highly reactive. So basically, you're dealing with two different types of products or particles in manufactured material and we have to be able to set up regulation for both.
And here is a copy of that slide, really what's so special about nanomaterial? If you look at how the property -- do you remember I said size and then properties. This is more related to the property. If you look at how nanoscaling a product can change its property, it can actually be dramatic. If it's insulator turning to nanoparticles can be a conductor. If it's insoluble, it can be soluble such as solvents that are used for drug delivery. If it's opaque, it can become transparent, such as the products in sun screen, and of course, the famous gold. What I will add here to what Dr. Martin said, is that if you look at this piece of gold and actually, we have received some drugs submissions based on gold particles recent to Health Canada, a piece of gold has a surface area. If the same piece of gold is turned into one nanometer gold particles, the surface area would increase by four million times, so, yes, you're dealing with a totally different property. And the surface area may be related to the reactivity of gold and so how do you assess such a tremendous difference in property. We are also doing, as I mentioned, research and we're producing products in Canada, a whole range of products, very diverse. Just some examples of products that are being currently manufactured or worked on at different institutes around different provinces in Canada, fullerenes, carbon nanotubes, quantum dots, dendrimers and nanomushrooms. And they have a whole range of other products coming up.
And not many of these products have actually held safety assessment or any type of initiatives associated with them, so they are being produced currently without any proper health risk assessment requirements. And this is something that we're currently looking into, is how can we classify them and encourage industry to at least provide us some of their own suggestions as how they want to go about the health safety assessment of these products and I'm going to show you in some slides how we're going about to do that.
If you look at this slide it's showing you actually the worldwide government nanotechnology funding. This is from 2004 and it's from an Australian report. If you look at 2004 and, of course, the United States, the amount of funding of 1.6 billion and if you look at -- sorry, I'm using this instead of the laser. If you look at Canada, it's about 200 million. Considering the fact that Canada has a tenth of the United States' population, I think per capita, we're doing fine. It shows that really the Government of Canada is considering nanotechnology as a very important project. We are spending a lot of money both on research and this is governmental funding, both on research as well as health and safety assessment.
So we are encouraged to set up new initiatives, ask for new funding and participate in international cooperation. So going into international activities that we are currently involved with, again, some of them are repetitious, but I can emphasize on some of the areas that Canada is actually leading in terms of research and setting standards. If you look at the OECD, we have been active with the OECD, working on manufacturing nanomaterial for a number of years now and we have subcommittees in Canada who work on specific subjects that OECD thinks that Canada can lead or can provide extra information. Same with Committee on Science and Technology. ISO, we've been very active with ISO and we have also subcommittee reports on some of ISO's priorities. Right now we have in Canada, we've considered setting up as -- we just heard from Celia that we consider setting up standards for new materials and classifications of these new nanomaterials, very, very important. This is our first step and so we are putting a lot of effort into working with ISO and setting up standards.
We're working with the International Risk Governors' Council, International Council of Nanotechnology as Canada's policies require. We're also very interested in global dialogue on nanotechnology with the Meridian Institute, US Science Foundation, international dialogues as well as Global Nanotech Network. So these are our current areas of international activities. If we go into Canadian federal activities, I'm just going to provide you with a few of the new initiatives and if you have questions later on, I can be available to answer.
We have, of course, the Public Service of Canada's Nanonetwork which is trying to put different ministries together and make connections between Industry Canada, Health Canada as well as some other non-profit organizations. We have a Nanotechnology Federal Action Plan which came out of a nanotechnology working group. The action plan is helping to set up the standards for classification and nomenclature and also trying to set up Health Canada with new regulations.
We've got granting councils in Canada overall. They've considered nanotechnology as one of their priorities and so a lot of grant money is actually going into nanotechnology research. That includes health research and safety and risk assessment. National Nanotechnology Strategy, which comes out of Prime Minister's Advisory Council on Science and Technology has actually been issued recently so we do have a strategy in place as how to go forward with nanotechnology and with the Federal Action Plan.
We continue here with our federal activities. We have a brand new national Institute for Nanotechnology which was set up. We just had a grand opening in June 2006. And here we do different types of research, ethical research, research on nanomaterial as well as risk assessments research. It's in Edmonton, Alberta. It's part of actually the National Research Council of Canada. The Institute for National Measurement Standards, this is the institute that works directly with the ISO and they are a lead on a number of projects as setting standards for nomenclature and classification of these nanoproducts. Standard Council of Canada, which is again, established a new ISO committee to work on terminology, nomenclature and metrology as well as risk environmental issues. And we've done public opinion research in 2005 and we're continuing to do new public opinion research. The main reason is to find out about integral issues conducted with the research.
Focusing on Health Canada, Health Canada is not a regulatory agency such as if you compared the FDA to Health Canada, Health Canada has a much broader mandate. It deals with a lot of other issues than food and drug, such as consumer product safety, disease and conditions, emergency environmental workplace health, air quality, climate change and contaminated sites, environmental contaminants, environmental health assessment, noise, occupational health and safety, radiation and water quality. And among these, I think the Federal Action Plan that I just mentioned is focusing more on the occupational health and safety at this time because we understand that a lot of researchers who are working on nanomaterial may be exposed to these substances, so we thought that this would be a good start to look at how these workers or researchers are working with this nanomaterial and what kind of procedures should we put in place to ensure safety of the workers.
So as you see, we not only have a food and drug -- responsibility for food and drug regulation, but also a very strong environmental mandate and because of that, Health Canada is now moving into looking at product cycle development more and more and to full cycle development of a product. And it's not only for nanotechnology, it's a general approach that Health Canada is taking under a new initiative called Progressive Licensing. And that means that we are -- if I give you an example of a medical kit, a diagnostic medical kit that has nanomaterial in it, if that kit is now being brought up to the market, we should be involved into the very early stage of development knowing what kind of nanomaterial is used.
We should assess it, do a review on this kit and ensuring that it's safe to use and then when it's disposing to the environment, we have to make sure that the disposal to the environment of this kit is not causing any harm to the environment. So we are looking at the full cycle development as well was you know, the disposal of this kit and this is a life cycle approach. If you're trying to apply to the majority of new material that's being -- coming to Health Canada for review, that's not only food and drug but hopefully the consumer products such as cosmetics.
We currently don't have a federal act regulating cosmetics but if a full cycle approach is approved and we're going into progressive licensing, those will come into effect, so they would apply to cosmetics as well. So in this connection, we have a few new nanoactivities at Health Canada. Just recent activities and what's happened recently to inform you about such as the fact sheet. We are going to set up a fact sheet and put in on our website shortly. We have an issue identification paper at Health Canada that's identifying all the gaps and all the research priorities that we need to look into. This paper has been now under revision, the last revision.
Health Canada's public agency working group to have an agency which does surveillance in Canada, surveillance of disease and surveillance of side effects of products that have already been approved. And there is a working group that's been formed between Health Canada and the public health agency. Research on assessing and characterizing toxicological effect of nanoparticles and that's basically what I told you about concerning our health and safety, worker safety, that's where we're doing our toxicological research. We find that ethical issues are of importance. We have an ethical research group in our new Center for Nanotechnology Research. Especially when it comes to new product development, we find that ethical aspects of new product development is to be very well looked into, so we have a few researchers in the new center working on ethical research.
Federal lead in nanotechnology, Health Canada is actually the federal lead in nanotechnology proposal to the Council of Canadian Academics, Academies and we're also -- we've been the federal lead in a workshop that we recently set up trying to coordinate nanoactivities across all ministries and non-governmental organizations. We have -- I'm not going to go through everything but we have a list of acts and regulations here that are currently supporting our review and assessment of nanotech-based products. Were using these acts and legislations to look into safety of nanoproduct, new nanoproducts. However, I must mention that we are also going, like the European Commission, through a legislative regime renewal process. That's another initiative at Health Canada. We're trying to reclassify the products and making sure the products that we're reviewing are in the right class and we're hoping that this legislative renewal will help us to better place nanotech products. And of course, we recognize that we have gaps in science. We don't have adequate science capacity. We have -- we don't know the impact on human health. We have lack of information on exposure. We don't know the appropriateness of our existing tools and as well as the rapidly evolving nature of the technology is not helping us.
I'm just going to conclude here with two points. Canada's current regulatory system regime can provide a framework for the advancement of nanomaterials and nanoproducts but there will be a need for modified regulatory and risk assessment approaches to better understand and that the international cooperation is extremely important and we need to be an active participant to minimize our duplicative effort. There is a list of websites, if you have a handout of my presentation in terms of the different ministries and organizations that are involved with nanotechnology research.
(Applause)
CHAIRMAN LUTTER: Thank you very much for the enlightening presentation. Our next session is the first of public stakeholders. It's entitled "General Science, Policy or Use of Nanotechnology Materials in FDA Regulated Products". And for expediency, we invite all six speakers to join us here on the stage. In alphabetical order, they are Dr. John Balbus of Environmental Defense, David Berube from the International Council on Nanotechnology, Carolyn Cairns from the Consumers Union, Kenneth David from Michigan State University and Dr. Stacey Harper from Oregon State University and Matthew Jaffe from the US Council for International Business.
Welcome, please, everybody today. And I have -- our schedule allows for eight-minute presentations. I think you can choose to speak from here at the podium or from there. It might be easier if you speak from here, especially if you have slides. And at the end, there will be a very short opportunity for the members of the task force to ask you questions. So, without further ado, we'll do this in alphabetical order, so Dr. John Balbus from the Environmental Defense is first.
DR. BALBUS: Thanks very much, Dr. Lutter and I'd like to thank the FDA and especially the Nano Task Force for giving me the opportunity to provide comments today. My name is John Balbus. I'm a physician and public health professional and Director of the Health Program for Environmental Defense. Environmental Defense is an organization formerly known as EDF or the Environmental Defense Fund. We're a large non-governmental environmental advocacy organization focused on science-based pragmatic solutions to environmental problems.
One of the hallmark of our work -- hallmarks of our work is our industry partnerships such as our partnership with Dupont on nanotechnology which Dr. Martin alluded to previously. Before I actually get into my slides, I just want to summarize my main points for the FDA.
The first is that as an organization, we very strongly support the safe development of nanotechnology because if its promise for tremendous advances for clinical medicine and energy production and material science and other critical societal needs. So our basic stance is promoting the safe development of nanotechnology. We are concerned, however, that because of limited authority and limited resources, that the FDA may not be able to effectively identify and manage risks from nanomaterials especially things like cosmetics, personal care products and sun screens. And lastly, we don't believe that the FDA's public communications to this point and other agency-wide responses really reflect the urgency and potential seriousness of nanotechnology risks and call on the FDA to devote more resources to improving its handling of nanotechnology concerns.
We'll see a slide like this many times today, I'm sure, pointing out the many different applications that all fall under the FDA's jurisdiction. My main point in showing this slide is not so much the variety of applications but to highlight the variety of legal authority and legal mandate that the FDA has in these different applications, ranging from very extensive pre-market testing and pre-market screening of pharmaceuticals, high risk therapeutics, medical imaging devices, and many food additives, to no pre-market screening and just post-market surveillance for things like cosmetic sun screens, and a reliance only on this post-marketing recall authority and voluntary industry activity.
The urgency I allude to is underscored by the fact that we have numerous products out on the market, people are using them. The materials are getting into water supplies, et cetera -- or waste water streams, et cetera. This is an old slide that shows that there were several dozen cosmetics, personal care products out on the market. I'm sure we'll see an updated slide later today from the Wilson Center showing these numbers increasing rapidly. And unfortunately, the FDA's public stance on this as at least alluded to the website, I think that we're seeing a different tone today here, but from the website, the public communications really don't inspire confidence in the process. The website states few resources currently exist to assess the risks and then kind of states flat out that particle size is not the issue and kind of long statement explaining how the FDA if very familiar with nanotechnology risks because all drugs, when you take them, go through a nanophase.
This is really not what we've heard from the other speakers today. It's not what we heard from Professor Ann Dowling and the University of Cambridge in the UK Royal Society Report who said quote, "Where particles are concerned, size really does matter and I think that we all recognize that it's the size of nanoparticles that makes us have to revisit the status quo". We will see other slides like this today. I'm not going to stay on this very long except to stress the point that because of the unique size of nanoparticles, they are a unique -- have a unique ability to interact with our biological proteins, essential biological machinery.
The top slide is just a modeling study of Javet, et al. showing that buckyballs are just the right size to be able to bond with and reconfigure DNA. We know that carbon nanotubes are used in DNA sometimes to separate them. There are unique interactions that we don't see with non-particulate bulk materials. One critical and yet, I think insufficiently answered question is the extent to which nanoparticles are able to penetrate the skin because this is really going to determine whether topically applied kinds of products will have systemic risks and be able to interact with DNA and so on like we were just talking about. Aside -- these slides here are just a study of quantum dots. The quantum dots which are going to be increasingly found in clinical settings, not so much in the personal care products, showing some modest penetration into the dermis depending on the coating that's used. The ME coating is a little more likely to penetrate deeper.
Critical questions of durability of these particles and other particles, fates of coatings as well as the persistence in excretion of absorbed particles are really going to be key to understanding the potential toxicity but as yet these questions are just starting to be pursued and we really think this needs to be a great focus.
And lastly, most studies that have been done so far on nanomaterials in the skin have been using in vitro preparations. And what's of most concern to me is the public health professional is not what these particular studies of cell culture show but the way in which these studies can be used and in some cases have been used to make fairly sweeping conclusions about the safety of the products for human use. Obviously, if you're just using skin cells in Petrie dishes, you really are unable to comment on the potential effects and the propensity of particles to get into systemic and lymphatic circulation and disrupt distant systems like the immune system, get into the brain, reproductive systems, et cetera. And so I just want to -- again, we need to answer these questions of where these particles go in the body, whether or not they can penetrate the skin in any kind of appreciable way and if so, then we need to be looking at systemic effects.
Environmental Defense has been working with regulatory agencies and industry partners to develop tools and methods to effectively manage the risk of nanotechnology products based on these four principles here. I'll get to the specifics for the FDA in a second, but I just want to underscore that really the hallmark of his is what Dr. Martin pointed out, is significant pre-market assessment, pre-market scrutiny, designing products with safety in mind up front and if you don't look, you won't be finding the potential risk that can be just engineered out from the start.
For the FDA, I think it's pretty clear we need to increase the level of risk research. As an organization, we've been calling for $100 million federal budget. There's discrepancies between different estimates. The government estimate is around 44 million now. I'm not exactly sure why the FDA showed up as zero, whether that was an oversight or -- because I know that the FDA is certainly involved in research. I'm not sure to what extent it's funding it, but we need to have a very significant ramping up in the near term to try to catch up with what's already on the market.
I think it would be very helpful for the FDA to seek pre-market authority for cosmetics and personal care products which it does not now have. Obviously, a long shot but there's no reason why we should just be counting the bodies and use that as our regulatory system. In the meantime, we can call on the FDA to maximize existing authorities. I think we need to revisit some of the weight-based exclusions under NEPA. Some of the considerations of NEPA are based on mass concentration. We can beef up the voluntary information programs that are currently used in cosmetics and I'm running out of time, so I'll just end that this is a great start that we have today. We have a great turnout. I think that we need to continue to increase meaningful stakeholder involvement and I look forward to being a part of it. Thanks.
(Applause)
CHAIRMAN LUTTER: Thank you very much. Our next speaker is David Berube of the International Council of Nanotechnology.
DR. BERUBE: First of all, I'm here today representing the Center for Biological and Environmental Nanotechnology. Vicki Colvin wanted to be here. She's on her way to India. She's a good friend of mine. I was on sabbatical writing a new book, and she says, "David, please do this for me," and I am.
Sun screens represent a multi-million dollar market and their consistent use is thought to reduce substantially the incidents of skin cancer. There will be no PowerPoint. I teach a course at Hatcher Electric called the Tyranny of PowerPoint. Titanium dioxide has been used as a sunblocking pigment since the mid-1990s and advances in nanotechnology just permitted the size of the pigments to be reduced below 100 nanometers. Similar advances were also applied to different materials, zinc oxide and today the estimate is about 30 percent of sun screen sold commercially contain these inorganic particles. The issue addressed here refers to two recent technical reports and in this month's FDA public commentary is whether shrinking the size of the pigments leads to any new toxicological properties.
A non-governmental organization, Friends of the Earth, released a report in May of 2006 characterizing the level of regulation of components of these sun screens as one of the most striking failures since asbestos. This September, the Cosmetic, Toiletry and Fragrance Association, the CTFA, a trade association, released a statement claiming, "The general scientific consensus is that there is no risk to human health". The statements from both these organizations demonstrate selective use of scientific literature and set the stage for an ineffective and polarized public dialogue on nanotechnologies risks and benefits.
The Friend of the Earth report presents a reasonably complete accounting of the recent technical literature but the technical review does not connect well with the ultimate recommendations. At several points in the report, the authors acknowledge conflicting technical data in the literature on nanomaterials' health effects but these nuances are not apparent in the report summary. For example, the report admits insufficient information about particle translocation across skin means the jury is still out, yet the report concludes regulatory negligence.
The Friends of the Earth analysis also generalizes from the specific cases of nanostructures found in one formulation to the behavior of all nanoproducts. Thus, the report cites groups of papers in one nanomaterial type, e.g. carbon 60, and then later in the report, refers to these results as the basis for taking action on all nanoparticle types. This tendency to over-generalize is particularly apparent in the report summary and in the more extensive policy recommendations laid out in the CTA legal petition to the FDA on behalf of FOE and the coalition of other advocacy groups.
The CTFA press release and associated reports shared with the FOE report a similar level of technical depth but draws very different conclusions. As in the Friend of the Earth report, there are disconnects between the CTFA's short public statements and the longer technical report. For example, the press release holds that the overwhelming weight of the scientific evidence states that these substances, referring to nanotitania are safe and untoxic, yet the full report from the same organization cites several publications that demonstrate oxidative damage in biological systems from nanoscale titanium.
In contrast with the FOE report, the CTFA report does capture the diversity of nanoparticle composition and the related diversity and biological response. In their analysis, however these data are used to justify a different over-generalization, namely, the size of these nanoparticles does not make them inherently different in terms of toxicity. The toxicity of nanoparticles will likely be cause for several physicochemical properties but this fact does not preclude size as being an important factor in defining biological properties for some systems.
Interestingly, both reports were in good agreement that the technical literature in many areas is equivocal. This is perhaps why the detailed reports are not substantially different and cover much of the same literature. What is striking is how each organization reacted differently to the current studies. Uncertainty was an argument not to regulate in one case while equivocation of the technical data was a sign that regulation must proceed quickly in another.
Vicki makes these recommendations. First, we urge all stakeholders permit the debate about nanotechnologies, risks and benefits to occur at the highest possible technical level. Secondly, all technical information used to form the basis for the first policy decisions in this area should be publicly available. The benefits of an open review at such a critical time in nanotechnologies development outweigh any possible loss to business due to confidentiality. We urge companies to not only make available toxicity and testing data ideally through peer review but also to provide data to support the efficacy of nanopigments compared to comparable organic materials. And finally, non-governmental organizations should continue to monitor the technical literature and highlight areas where more focused research is needed. Data bases such as the one offered by ICON on EHS publications should help and in time will contain even more integrative information.
Whether the benefits of using sun screens containing nanoparticle pigments outweighs their risks is a question not yet resolved in the peer review literature. We hope that while the science remains uncertain, government organizations like the FDA will base their policy decisions on a balanced analysis of peer reviewed and publicly available scientific literature. General principles of risk management which rely on good monitoring programs and investments in research are well-suited to these necessarily uncertain technical times. And as I mentioned, this statement was not approved as an official document of the International Council on Nanotechnology by its Editorial Board and should be considered the opinion of its author and the Center for Biological and Environmental Nanotechnology. Thank you.
(Applause)
CHAIRMAN LUTTER: Thank you very much. Our next speaker is Carolyn Cairns of the Consumers Union.
DR. CAIRNS: Thank you. My name is Carolyn Cairns and I'm a Senior Researcher in the Product Safety Department of Consumers Union's Technical Division. I also won't have any slides today, I'm afraid. As the non-profit publisher of Consumer Reports magazine, we appreciate the opportunity to share our views about the need for strong regulations to manage unique risks that can accompany nanoengineered substances and products within FDA's jurisdiction. We recognize the important benefits that these materials can bring to certain product sectors such as more effective medicines, safer drinking water and energy savings, but we also know that these benefits depend entirely on responsible development of nanotechnology.
We're deeply concerned that the unregulated widespread use of many nanoengineered substances, may generate the types of irreversible, unintended consequences seen before with other innovative materials such as PCBs and pesticides like DDT pushed to market before their risks were characterized. In cases like these, risk-based standards lag some 20 years behind their entry into commerce, often resulting in a long difficult and sometimes unsuccessful process to remove them from commerce, foods and the environment. That's what we don't want to see happen with nanoengineered materials.
It's precisely because of the potential benefits of nanotechnology are so heavily promoted even hyped in some cases, that FDA must increase its commitment to characterize and manage their hazards. We encourage FDA to revise its priorities to put greater emphasis on protecting consumers from nanotechnology's adverse effects than on removing hurdles that inhibit its use in commerce. Our comments today will focus on three basic points, many of which have been mentioned already. First, that FDA must understand that risk at the nanoscale can be size- and structure-dependent. Two, that regulations and standards based on mandatory pre-market assessments are sorely needed, and finally, the FDA must require disclosure through labeling of the use of nanomaterials in consumer products and transparency of toxicity information concerning these materials.
Although our concerns span a range of applications under FDA jurisdiction, my comments today will focus primarily on foods, dietary supplements, cosmetics and food and color additives. In our view, the first steps toward a coherent policy on nanotechnology is to recognize that risks of the nanoscale are often size- and structure-dependent and uniquely different than those of their larger counterparts. As has been mentioned already, experts in nanotechnology are virtually unanimous on this point and we think FDA needs to structure its approach to regulating these materials accordingly.
Scientists from academia and industry alike have raised many concerns about the impact of different chemical and physical properties that chemicals take on at the nanoscale, for example, their ability to cross the blood/brain barrier. Size and structural differences can also enable nanomaterials to migrate to different tissues and organs than their larger counterparts and elicit biological responses unique to their shape, worsen effects seen with larger particles. We're also concerned they may synergize adverse reactions with these or other substances and possibly impact the efficacy of conventional drugs and cosmetics.
Characteristics like increased bio-availability are particularly worrisome for substances for which no toxic effects levels have yet been defined or for substances like selenium where there's a narrow margin between the nutritive and minimum toxic effect level. Though many studies suggest that dermal penetration of nanomaterials is -- of some nanomaterials is limited, critical factors such as movement, exposure duration, and condition of hair and skin can influence findings. Researchers at National Institution of Occupational Safety and Health, for example, found that physical activity can move beryllium oxide into skin where it can activate cell mediated immune response which may lead to beryllium sensitization at lower concentrations.
Such findings may have implications for other immunologically active nanoscale compounds. FDA should also recognize the importance of size and structural differences on detection methods needed to find these substances in products, the human body and the environment. Accurate exposure and risk assessment and the consumer's right to choose all depend on such protocols, yet already -- such methods already required for food additives should also be required for nanoengineered substances. However, our own research suggests that some manufacturers have yet to develop reliable protocols for the nanoengineered ingredients they already sell.
Given the safety of nanoengineered materials cannot be predicted from their larger counterparts, we agree with the Royal Society and others who call for nanomaterials to be regulated as new chemical substances subjected to a full battery of safety tests and approval by government agencies before they're use. FDA needs to lead the effort to define this minimum battery of appropriate tests and work in coordination with other agencies like EPA and OSHA to insure that life cycle analysis -- life cycle impacts are fully characterized. Such protocols need to consider things like oxidative stress, C-reactive protein, platelet aggregation and other immune and inflammatory responses and genetic toxicity.
We're particularly concerned with now engineered ingredients in food, dietary supplements and cosmetics, products that completely lack pre-market safety testing requirements. Likewise, nanoengineered food and color additives currently require no special testing because FDA currently considers then equivalent to their non-nano counterparts. We think these products should be held to reasonable certainty of no harm standard that's already applied to food additives and pesticides.
Given the number of products that have already been in the marketplace, we think that new regulations also should be retroactive to cover existing products. Where critical gaps do limit the development of test methods, however, FDA should not be passive but should act quickly with expert stakeholders to lead and accelerate the development of appropriate test protocols relevant to new applications as they're being developed. We urge FDA to err on the side of caution rather than commercial expediency where scientific uncertainty is concerned. Though we appreciate industry's need for realistic protocols and standards that don't impede innovation, we feel that safe new foods, including dietary supplements, cosmetics and food and color additives are worth waiting for and most importantly, FDA should not take the lack of evidence of harm as a proxy for reasonable certainty of safety. We urge FDA to require labeling of nanoengineered ingredients and the products in which they are used and to act to fully inform and engage stakeholders in a debate over their use. Recent survey data show that consumers are not well-informed about the presence of nanomaterials in consumer products. Growth and demand for organic foods increasing at a rate of nearly 20 percent a year shows that many consumers already want to limit the use of synthetic materials in the products they buy and survey data suggests that many may feel the same about nanoengineered substances. Labeling is also crucial to facilitate exposure assessment and product tracing in the event of unanticipated effects and to enable assessment of cumulative effects that occur over exposure to multiple products. As a basis for labeling, FDA should undertake the difficult but important step to develop clear definitions and nomenclature for nanoengineered materials and nanotechnologies both for regulatory purposes and for minimizing consumer confusion.
We also urge FDA to develop mechanisms by which to fully inform and engage consumers and other stakeholders in meaningful dialogue about risks, benefits and unknowns associated with nanomaterials in consumer products. Consumers Union appreciates the opportunity to share our views today on this important consumer safety issue and we urge FDA to act quickly to adopt the recommended priorities and take a leadership role in developing the scientific research and regulatory tools needed to effectively assess, manage and communicate the risks associated with nanoengineered materials and to enable consumer choice in the marketplace through product labeling. Thank you.
(Applause)
CHAIRMAN LUTTER: Thank you very much. Our next speaker is Kenneth David from Michigan State University.
DR. DAVID: Good morning. This is a preliminary report indeed. We held our meeting on September 11th and 12th and I note from the slide that it's really characteristic of this team that I didn't even put my name on it. This is a well-integrated team. We have a sociologist of standards, Larry Busch, a philosopher of science and technology, Paul Thompson, myself, I do organizational analysis, organizational anthropology, an engineer, a mechanical engineer, Jack Lloyd, an applied anthropologist, John Stone, Susan Sulke in packaging and this is a team effort.
Now, this, I repeat is a preliminary report. We do have a website and we have already work from our previous international conference on that site and if you want this, I hope you will look at it by about November 15th and give me a business card if you want a reminder. Let's get at some overall findings of the workshop.
We had participants, government agencies, non-governmental agencies, companies, industry associations, universities, and we find that nanotechnology gets people to react in very distinct ways to nanobenefits and nanofears. Some find it a desirable destination, some find it a gathering storm, some find it awful and terrifying, a challenge and a threat, and others find it a clear and present danger. All are present. We entertained in our group the representations of proponents and opponents of nanotechnologies. We have had that in all of the meetings and we put together a group of people, put them into small work groups where we debated a number of themes relevant to nanotechnologies and standards.
First, let's get a second finding. When one hand standards are considered convenient, neutral and benign means for handling issues of technical compatibility, they are then a social construction of reality. We wonder, the group did, whether the effectiveness of this social construction will be tested by processes of knowledge transfer among the governing agencies. Of course this is something that Celia Merzbacher addressed. We wondered where is the coordinating framework for nanotechnology with evaluating regulatory teeth as was developed more for genetically modified food.
It's not just a social construction of reality standards are also power construction of reality, you know, setting rules that others must follow. Standards are a form of codified social power that reflect interests of group with the greatest access to the standard-setting process. It is thus a source of strategic advantage at the local, at the national and at international levels. We recognize power processes at work among countries, sometimes of collaboration and cooperation and sometimes of competition. We note the impact of the CEN influence, one country, one vote in forwarding proposals to the ISO. We note that the US was not the earliest in responding to ISO 9000 and I don't think that makes a difference. We note that China also was slow in responding in building its own answer to Codex in food definitions and then adopted them wholesale.
So if you get there first, it makes a difference. And we did analyze the topic of nanotechnologies and standards in five themes; read quickly, timing in standard, product standards and process standards, very tricky one, international harmonization of standards, integration of operational standards, a very good topic. Wish I could spend more time on that, and finally participation and transparency. And as I tell my students, if you have too much to say, choose just a bit, and that's what I'm going to do, just something on the timing.
Timing relates to the public, to competitors, and to international standard-setting bodies. Should the standard setting process begin early in the knowledge development process, or later as such knowledge is applied to products and processes. The uniqueness of nanotechnologies, of course poses problems. Maximum residue levels have not firmly been established. We know already that ANSI and ISO are developing nomenclature to describe nanotechnologies and of course, we heard earlier instrumentation metrology directions are being developed. It's all on the way.
We note also that that progress is hindered because resources for risk assessment are low. The supplement to the President's 2006 budget recommends 1.05 billion for overall NNI investments and as we heard earlier, only 82 million of this is for societal dimensions, specifically environmental health and safety, R&D, education, ethical, legal and other social issues. This is perhaps a big figure in one sense but compared to the overall investment, it's not the biggest.
Next, regarding engagement between the public, the scientific community and standard-setting bodies, timing is critical. I should note here that I'm a co-author with a senior research scientist at Shell and it is his point that early engagement is historically put, if you do a history of science, quite unreliable, that the ability to predict impacts at the very early level of scientific discovery doesn't work very well. Partially, the issue is that resource allocators in firms require a series of research statements and then they make go/no-go decisions. The early statements are very, very brief. They are just relevant to whether or not the product or the scientific idea fits with the strategic work of the company but are certainly not yet explicit enough for upstream engagement.
It becomes possible when a scientific idea is developed and becomes closer to the notion of applications, products and processes. There's also a late barrier. As we saw in Britain when they summoned the GM nation, genetically modified nation, the late engagement alienated the public. It was just looked at as a marketing exercise. Timing, and here's something, perhaps to be considered by business people in the room, it's also critical regarding business competitors and international standard-setting bodies. If you wait too late to get in on the standard setting process, you allow competitors to get there first and that may rule you out, set up competitive barriers and the same point, as I said before, works towards working with international bodies such as ISO.
Now, I'm just going to show you something that is a conclusion, an analytic diagram that describes findings just described as other findings to be reported in our full report. It is complicated but the idea is here for the FDA and for all other agencies we consider the standard-setting and regulation to not be considered by itself but is one of four major issue areas that is we are underway to explore and my time is just up. I thank you for your attention.
(Applause)
CHAIRMAN LUTTER: Thank you very much. Our next speaker is Dr. Stacey Harper from Oregon State University.
DR. HARPER: Do you start this or do I start this?
CHAIRMAN LUTTER: Can you control the slides from the control room at the back of the auditorium, please?
DR. HARPER: Thank you. Sorry. Okay, I'm here on behalf of the Oregon Nanoscience and Microtechnologies Institute to tell you a little bit about the safer nanomaterials and nanomanufacturing initiative that we've developed and I want to present to you our proactive approach to actually designing nanomaterials that are both safe and have enhanced performance. Now, it's undeniable that there's going to be widespread applications associated with the nanotechnology industry but given this exhortation, there's growing concerns about the biological activity and toxic potential of these novel materials. The unique properties the industry sometimes wants to see in a material may pose serious health risks but the lack of data in this area makes this completely unpredictable at this point.
And then the last issue is, even if there are no inherent risks or toxicities associated with nanomaterials, the public's perception of that is not going to be realized until the toxicological studies are promoted in concert transparently with the development of novel materials. Nanotechnology offers us the opportunity to use the precision engineering to both modify the properties that industry wants and to make sure that they are safe and benign for the environment and human health.
In the Pacific Northwest we have about 26 researchers working on the safer nanomaterials and nanomanufacturing initiative. Our main goals are -- what did I do? Okay, sorry. Our main goals are to develop safer and better nanoparticles using less wasteful nanomanufacturing methods. And I want to talk about this for just a second, but I'm going to focus on the better and safer nanoparticles for the most part. But the less wasteful manufacturing is also one of the key elements of the safer nanomaterials and nanomanufacturing initiative where we're trying to reduce waste using the 12 principles of green chemistry to actually direct the manufacturing portion of nanoparticle synthesis.
And then we're developing ways in which we can integrate these into high performance devices without the use of excess solvents and such. So here's our design strategy for developing these safer nanomaterials and up here on the right we have nanoparticle -- average nanoparticle. It has a core, some sort of stabilizing shell and then some functional groups on the outside. Basically, the chemicals or the synthetic chemists give us materials that they have produced that have the properties that they desire. They give them to us and we test them in a multitude of biological systems to assess their toxicity.
And we feed the information back to the synthetic chemists. If we get something that's highly toxic in the first assay that we run or the first in vivo exposure that we do, we send it back to the chemist and say, "This isn't going to work". They resynthesize it and we're trying to get this to a point where we can actually develop some of these structure/activity or structure/property relationships to use -- to then direct the development of safer nanomaterials.
And these structure/property relationships, the goal then is going to be link the physical chemical properties of the material, either surface area, structure, charge, things we probably haven't even thought of yet, with any hazards that are posed by the material. Okay, nanoparticles have widely tunable properties. So it is feasible to enhance performance and safety at the same time and that would probably be my biggest take home point.
Now, in order to test the biological impacts of these new engineered nanoparticles, we take a tiered approach where we start by doing screening level toxicity evaluations and at this level we test in cell cultures, tissues and in whole organisms, using a multitude of platforms and assays both in vitro and in vivo, so that in the end we aren't just looking at what one animal's response or what one's cell types response was to these nanoparticles. We can look across a whole suite of assays and get at the basis of, is this going to be harmful or not and use kind of a weight of evidence approach.
Now, if these materials are found to be potentially toxic at this screening level, then they go on. We send them back and they go on and we have people that work in the group that are mechanistic- type people so they want to identify some of the cellular targets and get more information about these materials. We define these in vivo using whole animals using fluorescently labeled nanomaterials or very targeted assays where we can look in vivo. And then finally, the nanomaterials are grouped either based on some chemical property of the material or some effect that it elicits and when they're grouped then we take the groups together and determine gene expression profiles for those materials and see if there's any consistency across there.
All of this information is then stored in a nanomaterial effects data base and it's used primarily to feed back to industry in order to hopefully in the future to be used to direct this development of safer nanomaterials.
Now, we're started running some of these toxicity assays and compiling structure/activity relationships for a well-defined library of gold nano particles. I'm glad some of the introductory speakers spoke of gold nanoparticles, so I won't have to get into that at all. Thus far we have 1.5 nanometer and .8 nanometer core sizes and we have a whole variety of surface functionalizations on them. And using this iterative approach, we are going through and trying to figure out what are the common things when we get a toxic response, what are the common things among those particular materials? So now I want to give you a very specific example, just to illustrate some of the key components of our research strategy.
So this is an example of how the toxicity assessments can be used to help identify the relative importance of various parameters for the toxic potential of the material. And for simplicity's sake I'm just limiting this to size and surface functionalization and we're just going to look at it in reference to a positively charged versus a negatively charged and two different sizes. And keep in mind that I'm just going to be showing you mortality in whole animal embryonic zebra fish assay, so this -- if you add this to all of the suite of experiments that we've done on these, there is some consistency with these ones, but there are some materials that you see no mortality and you see a lot of tratogenicity and it's more in-depth than that.
Okay, so this first figure shows us mortality of the embryonic zebra fish that have been exposed for five days to the 1.5. size nanoparticle that has positively charged surface groups. And you can see here at 10 parts per million, this is highly toxic and kills the animals. Now, if we look at the smaller size, the 0.8 nanometers, we see that this toxicity curve moves down to the left and at 400 parts per billion, we're seeing toxicity. So the smaller nanoparticles that are these particular nanoparticles with this particular positive surface functional group, are actually more toxic when they're smaller. So size does matter in this case.
Now, let's look at the same size nanoparticles but with a negatively charged surface group. So this one shows that these are practically benign. They're not highly toxic to -- in this particular assay. And when we shrink these down to the smaller level, any guesses? Nothing. They're benign also. And how general and how we're going to be able to figure out what generalizations we can make about these nanomaterials is going to be, I think, more difficult than it has been for chemicals because we do have this core, this surface functionalizations and the stabilizing shell.
CHAIRMAN LUTTER: Could you please finish up in just the next few --
DR. HARPER: Yes. Our general -- our recommendations are that characterization and purification need to be done very carefully so that these structure activities are very robust and we need to identify the biological and environmental impacts for safety and design and then finally the toxicological evaluations need to be incorporated early on in the research and development scheme. Here's our contact information. I'm going to leave some brochures out on the table, too, for the safer nanomaterials and nanomanufacturing initiative.
CHAIRMAN LUTTER: Thank you very much.
(Applause)
CHAIRMAN LUTTER: Our next speaker is Matthew Jaffe of the United States Council for International Business.
MR. JAFFE: Good morning. Again, my name is Matthew Jaffe. I'm a partner in the law firm of Crowell and Moring here in Washington DC and it's my privilege today to appear and present the views of the US Council of International Business on this important subject. My presentation today will address three points stemming from FDA's announcement. First, I will provide a brief outline of USCIB's involvement and initiatives in the area of nanotechnology. I will then speak to our understanding of current efforts and needs related to understanding the environmental health and safety implications of nanoparticles. Finally, I will address the important role that USCIB anticipates the FDA will play in promoting and protecting public health with respect to FDA regulated products that use nanotechnology materials.
Founded in 1945, the membership if USCIB now includes over 300 multi-national companies, law firms and business associations. USCIB has built a reputation for reliable policy advice and has helped to shape international regulations and expand market access for US products and services around the world. For example, through our membership in the Business and Industry Advisory Committee, that's BIAC, USCIB provides industry leadership on key OECD activities, including critical work now being undertaken by the OECD's Science and Technology Policy Committee, and Chemicals Committee on nanotechnology policy and regulatory activities.
As you may know, the OECD just recently established a working party on manufactured nanomaterials under the jurisdiction of the Chemicals Committee. The working party's first meeting will be held later this month in London and USCIB members will be there as part of the BIAC delegation. Why the interest? That's simple. For USCIB and its members, for the business community at large, nanotechnology looks to be a critical driver of innovation and economic growth in the 21st Century. As important, it potentially represents a transformative set of technologies.
The dynamic nature of nanotechnology thus makes it imperative that governments, businesses, academia and the public at large get the policy framework right to realize the enormous economic, technological and societal promises offered by nanotechnology, which brings me to my second point. Most of the attention that has been paid to nanotechnology to date has centered on its tremendous possibilities and thus, issues generally related to the research and development for practical applications. Lately, there has been a shift toward a recognition that we need to know more about what this research, what this development will mean in the context of environmental health and safety effects. Last month's hearing before the House/Senate Committee certainly highlighted the importance of a shift but it did not constitute the first steps in that direction. We've heard already today and in the international arena the International Risk Governance Council surveyed government, industry, non-governmental and risk research organizations and published results that split nanotechnology product development into two broad frames of reference for which it suggested separate yet complimentary research and decision making pathways.
Well, of course, then the OECD is also considering a draft program of work on the safety of manufactured nanomaterials which is likely to establish priorities. In the United States there are inter-agencies and agency studies, research studies and industry studies like the NNI chemical industry's roadmap of important issues to consider during the first phase of nanoparticle research. And then there are other groundbreaking efforts in the private sector, like Dupont and Environmental Defense's collaboration. In other words, to borrow from Dr. Alderson's response to the House/Senate Committee, we have all heard the cause for greater research about the possible EHS effects of nanoparticles loud and clear. With that said, we should not draw conclusions about nanoparticles before we conduct the research. We have been surrounded by natural nanoparticles for eons. The European Commission reports that a room like this one may contain 20,000 natural nanoparticles per cubic centimeter. And in this context, humans have developed natural response mechanisms to nanoparticles.
It is thus, critical that in this process of developing a policy framework that we strike a balanced approach to questions concerning the effects of nanotechnology, that we do not generalize, that we measure benefits along with risks and that we base our conclusions on verifiable science, which leads me to my last point.
What is FDA's role in all of this? What regulatory approaches should it take to encourage the continued development of innovative, safe and effective FDA-regulated products that use nanotechnology materials? The FDA already has in place a comprehensive regulatory system founded on scientific principles and evaluations. These systems allow the FDA to review regulated products in a manner that safeguards the public against risks at the same time it recognizes the need for our society to benefit from the enormous potential that these products have to offer.
We, thus, strongly encourage FDA to regulate applications that use nanotechnology according to the same guiding scientific principles that have already allowed this agency to effectively protect, promote and improve public health. Again, the dynamic and complex nature of nanotechnology makes it imperative that governments, that all of us get the policy framework right. Like any new technology, there's some uncertainty, uncertainty over environmental health and safety effects. The USCIB believes the OECD is prepared to play the critical role at this juncture and we invite the FDA to actively participate in the OECD process together with your colleagues at other agencies. Building on the significant expertise and chemicals policy and regulation, the OECD is ideally placed to develop internationally agreed science based methodologies, definitions and mechanisms for managing products and for protecting environmental health, human health and safety. FDA's internationally knowledge and expertise in public health makes it well-suited to interface with OECD and others to share its knowledge. Thank you.
(Applause)
CHAIRMAN LUTTER: I'd like to take a few minutes to ask the members of the FDA's task force whether they have a couple questions that they'd like to put to members of the panel here and then after that we can turn to a break. So we have benefitted from six very informative presentations and I wonder if somebody would be brave enough to put a question to the speakers. Eric? If the mike doesn't work just ask the question, Eric and I'll repeat it.
DR. FLAMM: Thanks. I'd like to direct a question to Mr. Jaffe. In light of the earlier speakers' comments on the lack of knowledge of how certain materials work at the nanosize and lack of pre-market oversight of certain areas of FDA jurisdiction, and in light of your statement that FDA should maintain its science-based approach to regulation of product, what is your view of the adequacy of FDA's authority over products like cosmetics?
CHAIRMAN LUTTER: If you could take just a minute, thank you.
MR. JAFFE: This is Matthew Jaffe again. I'm appearing on behalf of the USCIB, so obviously, I don't have the authority to speak on behalf of the USCIB in response to your specific question because it's a large organization. However, I would note, again, reference my comments which we said specifically that we believe the regulatory process that is in place currently is significant and adequate to address the issues that are currently before the FDA on issues of cosmetics and other items as well.
DR. CANADY: Hi, this is Rick Canady with the Office of Commissioner of the FDA. Actually, I have two questions. The first one I don't think folks are going to be able to answer very quickly so I'm probably going to go to the second one real quickly. The question is with regard to presentations by Ms. Cairns, I think, John Balbus, even David Berube, there was -- there were questions about uncertainties and questions about definitions and so on with regard to what we can label, where we can label it and so on. And I just wondered if you had any further insight about how we start that process of developing definitions that allow us to label, for example, allow us to know when nanotechnology begins and how to inform consumers and then Ms. Cairns, if you could respond and then I have a question for Dr. Harper.
DR. CAIRNS: Yeah, that's really, obviously, a complex and very important question, where do we start, and I think we're thinking about it from the standpoint of somewhat the way the folks in the University of Oregon are taking it, there's a tiered approach. I think there's a lot of -- a lot that we know now already from some of the work that's already been done. It's very limited but it's not zero. And I think if we can take that tiered approach and start with some basic get -- pull this information together, and really see what do we know.
I mean, I think just at the bottom line, if a product is being engineered at the nanoscale, that right there opens the door that you're specifically manufacturing something to have these properties. We need to know what those properties are, where that chemical is being used and how people are being exposed to it, so that, I think is the first step.
DR. BALBUS: You're really asking two questions. The first is what are we going to use as a definition of whatever it is we want labeled, whether that's nanotechnology, nanoparticle. That's proving to be pretty thorny and there's a lot of different venues in which that debate is going on, whether it's ASTN, ANSI, EPA, et cetera, and I don't have an easy answer on that.
The second part is, should manufacturers be disclosing to the agencies when they have whatever ultimately gets determined to be the definition of a nanoparticle. And we saw kind of the down side of loose labeling with the Nano Magic episode last April where companies are allowed to put the word "nano" on the product, not the three different industries of companies involved. The disclosure wasn't good. It took them months to actually figure out if there was anything that was anybody's definition of a nanoparticle in the product and ultimately there wasn't. So I think the FDA has the ability to call for claims and marketing claims and you know, it would be incumbent on you to define exactly what would be a nano, you know, marketing claim and not, drawing from the work that's going on in a lot of standard setting organizations.
DR. DAVID: Richard, the only thing I want to add is that I'm a big fan of research needs assessment anyways and I think everybody realizes that needs to happen, but when we do this, we also have to throw a threshold parameter into it because scientific research is boundless. We all know that. We could always be waiting for more information. We just have to figure out when enough is there to actually make a decision. And the last thing, since I'm a professor of risk communications that you know, you're going to have to communicate this to the public while it's going on, I mean, because the public is getting a lot of bits of information right now and they're trying to ferret their way through it and having an incredibly difficult time.
And so we don't just need to figure out, you know, what's safe and not safe. We also have to try to figure out how to be able to communicate that to the public while all this is going on.
CHAIRMAN LUTTER: Please join me in thanking the panel for this very enlightening presentation.
(Applause)
CHAIRMAN LUTTER: We have a break of about five minutes and then after that, we'll start again.
(A brief recess was taken at 11:11 a.m.)
(On the record at 11:22 a.m.)
CHAIRMAN ALDERSON: Well, this follows -- this is our second session and I just want to remind the speakers that you have eight minutes and at seven minutes the yellow light will go on. At eight minutes, Randy and I will get itchy over there and if you continue on we'll then beep you. So you know, if you've reached that point you're in trouble. So let's get started.
Our first speaking of the second session is Martin Philbert, from the University of Michigan, School of Public Health.
DR. PHILBERT: Good morning and thank you for the opportunity to speak with you today regarding the science of nanotechnology. I'm Martin Philbert, Professor of Toxicology and Senior Associate Dean for Research at the University of Michigan, School of Public Health. I also serve as the Executive Director for the Center for Risk Science and Communication or CRSC.
My primary area of research includes development of nanosystems for measurement of physiological processes within living systems, including cells and for the early detection and treatment of brain tumors. I look forward to assisting the FDA in furthering its understanding of nanotechnologies that fall under its purview. Nanotechnology holds great and varied promise in contributing to significant improvements in public health. However, as with all emerging technologies there are inevitable risks accompanying the development and deployment of nanomaterials that must be considered. As we continue to explore this emerging science, issues surrounding health and safety are certain to arise. But what I want to emphasize to you today is that the scientific community is not completely ignorant with regard to hazard identification, risk analysis and to the management of those risks associated with the deployment and the use of nanoscale materials.
And the take-home message is, essentially, there is no need to panic. In fact, over-reaction is likely to stifle innovation, prevent advancements in nanotechnology and rob the public of potential dramatic improvements in health and the amelioration of suffering. Simply stated, at present the benefits of using nanomaterials greatly outweigh the risks. Any steps in policymaking must be based on a sound foundation of scientific evidence and in my opinion the science does not yet mandate Draconian action.
I want to describe in brief what I view as the state of the science of demonstrable adverse effects induced by nanoscale materials. We've known for some time from the published evidence, the peer review published evidence that comes from exposure to ultra-fine materials and to some of the more novel materials that high aspect ratio materials, i.e., long thin fibers tend to make things more reactive and more damaging. If these materials are also bio-persistent, and have reactive points that are also associated with transition metals or other metals that are capable of producing reactive oxygen species, that greatly enhances the likelihood of toxicity.
Now, it is not -- at the risk of being heretical, it is not the nanoscale necessarily that confers toxicity. It may enhance toxicity but nano is just a scale. In fact, one has to wonder whether or not as the cadmium, selenium or arsenic associated with a quantum dot-like material that is the toxicant or its size and whether one needs to reduce the overall exposure to those materials. We also know we have learned a great deal of lessons from manganese exposure and welding fume with materials at that nanoscale. We also know how to manage these risks. Coating materials with bio-compatible chemicals or other polymers greatly reduces their toxicity and this has been published with regard to Dextran and silica titanium dioxide and zinc oxide, et cetera.
We've also known for many years that polyethylene glycol alters the pharmacokenetic and toxicokinetics profile of materials in drug delivery vehicles. Nano is just a scale. The nanoscale does not per se or of necessity confer any uniform or specific physical property. Neither does it automatically denote advantageous or adverse health effects. It is important to note that it is not the nanometer scale of the material per se that can pose the potential for toxicity as evidenced by work performed at the University of Michigan CRSC.
What you see here is essentially negative pathology produced by a 60 nanometer polymer. This is a polyacrylomide hydrogel that was delivered in doses of either on the left two panels, 10 milligrams per kilogram or on the right 500 milligrams per kilogram, half a gram per kilogram intravenously into a rat without any evidence of toxicity by pathologic or clinical chemistry in any of the tissues examined and we looked at 32 tissues. And this is a nanoscale polymer. So generalizations are generally unhelpful. If, however, we loaded that material, the benign nanomaterial, with iron oxide which we know produces superoxide, then the toxicokinetics profile changes but at very high doses. In fact, we saw toxicity in an intact animal, this is an in vivo model, and we see toxicity in the kidney and liver after exposure to these very high levels.
In fact, there was no credible scientific evidence at this time demonstrating that in the current mode of use in the current mode of use engineered nanoparticles pose an uncontrollable or eminent threat to the health of the public. Any assertion otherwise simply does not stand the test of scientific scrutiny. We need to be vigilant in pursuing these scientific endeavors but we can also build on what we know to be true. Nanoscale materials have been with us for a very long time and human exposure to these substances provide us with valuable lessons.
Nanotechnology will soon be a trillion dollar plus global business enterprise with a potential for enormous health benefits but may also prevent -- or present adverse health risks. The benefits derives from nanomaterials are far-reaching. For example, NCI has invested in the University of Michigan and other academic centers to develop cutting edge technologies that will change dramatically our ability to detect the earliest stages of cancer and to manage and cure diseases for which the current standard of care is inadequate. The key is to manage the risk while deriving the maximum benefit from the use of these materials.
For example,
the very same material that at 500 milligrams per kilogram produces that frank necrosis
of the renal cortex and the hemorrhagic change in the liver gives us unprecedented
views of an orthotopic tumor in the second panel, you can see the tumor highlighted,
after a single intravenous injection of 1/100 -- actually it's 1/500 of the dose
that produces the toxicity. And as you can see in Panel C, you not only
see the tumor itself but you get very clear views of the vasculature immediately
adjacent to the tumor and this highlights a very interesting and contradictory
point here or a point that contradicts much of what has been eluded to in earlier
presentations.
That is that the
blood/brain barrier prevents access of this nanomaterial into the brain tumor
and so it is not fair to say that this would automatically gain access. If
we use exactly the same material, we can ablate the tumor as seen in this live/dead
panel only within the radius of the laser that illuminates these cancer cells
do we get cell death and in a tumor model, which is uniformly lethal at about
10 days, we see that we get about 40 percent survival and these animals are alive
at about 50 days. It would be
wrong for us to over-regulate. As we saw in the case of ALR, consumer
panic was later found to be unwarranted and it is now being called one of the
greatest unfounded health scares of the last five decades. This is a constant
reminder that we, as scientists, policymakers and regulators, need to engage
in the business of protecting the health of the public with all due diligence,
urgency and caution. I've spoken about the state of the science, the benefits
of nanotechnologies to human health and we need to avoid over-regulation while
remaining vigilant.
I look forward to working with you, with my other colleagues and with the CRSC at the University of Michigan in further exploring this interesting and important issue. Thank you.
(Applause)
CHAIRMAN ALDERSON: Our next speaker for this session is David Rejeski from the Project on Emerging Nanotechnologies.
DR. REJESKI: Well, thank you. It's a pleasure to be here. I'd like to thank the FDA for inviting me. Why do public perceptions matter with nanotechnology? Let me sort of take you through some arguments. Public perceptions matter right now because the public is coming in contact with more and more products that are at least according to manufacturer's claims, based on nanotechnology, and many of these are under FDA purview. Our inventory on nanobased consumer products now has over 320 products in it from 17 countries, an increase of 100 products in less than six months.
The largest increase is in the area of cosmetics. Dietary supplements are also up. Food has remained level except products that are now in contact with food have increased dramatically. There's also a number of drugs and biomedical devices that are emerging and we started a separate inventory just to cover those. We recently met with some researchers in Japan who have launched a similar inventory. Theirs contains over 200 products. Almost half of those are cosmetics, 10 food products.
Most of you know that there's a lot at stake here. Over $10 billion is not being invested annually by the public and private sector in nanotech R&D and here's some of the market numbers and projections in areas that FDA regulates including nanotherapeutics, drug delivery devices and also food. I'd point out the number of nanobased drugs and biomedical devices is, according to some estimates gone up about 70 percent in the pipeline, clinical pipeline over the past year, again, obviously a lot at stake.
So what can we say about public perceptions in the FDA and nanotechnology? I think the first important piece of data is that public confidence in the FDA is down. And it's down precisely at a point in time when more and more nanotech products are beginning to penetrate the marketplace. This is six years of data. However, the story is, I think, a little bit more complicated and somewhat more subtle. In August we conducted a national survey of over 1,000 adults and asked people who they trusted to maximize the benefits and minimize the risks of scientific advancements. The FDA came out below the USDA but it came out above EPA and far above industry. People are fairly ambivalent about industry's abilities, so trust in FDA is down. However, the agency is nevertheless, I think has a lot of standing, especially when compared to industry and I think that's standing that can be used over time to build trust.
We asked people specifically who should monitor cosmetics for safety and effectiveness. People chose the government and independent researchers again above industry. In fact, only 12 percent trusted companies alone to monitor safety which is essentially what happens now. The survey also pointed to some important differences in risk/benefit perceptions, I think, which are relevant to FDA or anybody that's introducing nanotech into the marketplace. I think one of the most important ones is related to gender. After we provided participants with information on nanotech applications and potential implications, women were far more likely to focus on risks than men. Okay, this is something called the white male effect. It's been known for years. It's nothing new or surprising.
One expert in risk research once noted that a substantial percentage of white males see the world as so much less risky than everyone else sees it. Maybe this is a plea for gender balance in our regulatory agencies. However, I think this is important because a lot of the nanobased products on the market FDA has some oversight on, why, cosmetics are purchased primarily by women. Also, women are also, I think, primarily responsible for many of the food purchases in the home and nanobased or nanoengineered food is coming and it's coming very quickly. In August we ran two focus groups right in Baltimore just with women to probe their attitudes toward nanotechnology, especially in relationship to cosmetics. One of the most stunning findings was that none of these women realized out little oversight FDA has on cosmetics, none of them.
They all overestimated the level of FDA's oversight on cosmetics, exactly what they could do, what kind of test they could do, whether they could recall products, and at the end of the two hour sessions, we asked them what they would say to FDA or industry if they got them in a room and these are some of the remarks, and I think these are fairly representative of what we've seen in a lot