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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`FOOD AND DRUG ADMINISTRATION
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`NANOTECHNOLOGY TASK FORCE
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`PUBLIC MEETING ON NANOTECHNOLOGY MATERIALS IN FDA REGULATED PRODUCTS
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`Tuesday, October 10, 2006
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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, cochairmen, presiding.
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`PRESENT:
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`NORRIS ALDERSON COCHAIRMAN
`RANDY LUTTERCOCHAIRMAN
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`CONTENTS
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`AGENDA ITEM PAGE
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`Welcome 3
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`National/Regional Perspective
` Dr. Celia Merzbacher 13
` Dr. Philippe Martin 25
` Dr. Delara Karkan 37
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`Session 1:
` John Balbus 50
` David Berube 57
` Carolyn Cairns 62
` Kenneth David 69
` Stacey Harper 74
` Matthew Jaffe 82
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`Session 2:
` Martin Philbert 92
` Dave Rejeski 99
` Michael Taylor 105
` Bruce Levinson 112
` Kathy Jo Wetter 114
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`Session 3:
` Pascal Delrieu 129
` Jane Houlihan 134
` George Kimbrell 140
` Erich Pica 147
` Michael Roberts 153
` Annette Santamaria 163
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`Session 4:
` Phillip Buckler 175
` Neil Desai 180
` Anil Diwan 188
` Piotr Grodzinski 194
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`Session 5:
` Deborah Ledenheim 205
` Bernie Liebler 211
` Scott McNeil 218
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`Session 6:
` Lutz End 226
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` PROCEEDINGS
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`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
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`Lutter, CoChair of FDA's Nanotechnology Task Force and my CoChair, 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 FDAregulated products and
`today we're looking forward to an informative and wideranging 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
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`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 premarket and postmarket 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 nanotechnologybased 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 noninvasive 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 FDAregulated 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
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`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
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`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
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`nanotechnology materials in FDAregulated 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 FDAregulated 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 FDAregulated
`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
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`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.
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` 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 email 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
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`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
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`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 interagency 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
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`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.
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` 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 interagency 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.
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` 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, crossagency 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
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`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 riskrelated 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 interagency group that I cochair felt that, in fact, greater
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`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 selfexplanatory 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
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`it also will inform and guide the research agencies as they plan their
`programs and budgets. But it's not really a governmentspecific 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 fastmoving 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
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`Agency has announced a public meeting on risk management practices within
`the scope of a possible stewardship program that the EPA is exploring.
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`That's scheduled for October 19th and 20th here in Washington, DC and you can
`find more from the EPA website.
` There are also nonprofit 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.
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`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
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`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, interagency bodies
`don't set the budgets. That's done at that agency level; but the work of
`the interagency 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.
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` 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
`h