Category: Drugs

ref1394_x180-fThe National Academies have promised a report by the end of January 2012 on priorities (both short- and long-term) for studying the health, safety, and environmental effects of nanotechnology.  According to the National Academies, this report will address the following matters:  the properties of engineered nanomaterials; methods and technologies for “detecting, measuring, analyzing, and monitoring” engineered nanomaterials; what studies are needed; what testing methods need to be developed; the models for predicting impacts that should be developed; research priorities; and the criteria for evaluating research progress.  In its “Statement of Task,” the National Research Council has explained:

“The committee will take into consideration current and emerging uses of engineered nanomaterials and the scientific uncertainties related to physical and chemical properties, potential exposures, toxicity, toxicokinetics, and environmental fate of these materials.”

I will discuss the report when it is issued.  More information on the National Academies’ research strategy is available at

This is a promising developing to look forward to, but as with all things, the proof is in the, er, nanopudding (sorry, couldn’t resist).  Initiating a task such as this is daunting, with the result a framework for assessment, not the ultimate assessment.  But it is a necessary step in what is certain to be a long process.

In a separate project, the National Academies are considering more than the health, safety, and environmental effects of nanotechnology.  Pursuant to the Nanotechnology Research and Development Act (Pub. L. No. 108-153), Congress has mandated triennial reviews of the National Nanotechnology Initiative (NNI).  The National Academies’ National Research Council convened a committee to conduct the second such triennial review, and its report is due in 2013.  Much of the review will entail examining the economic impact of nanotechnology and ways to measure the value of nanotechnologies.

Information on the triennial review project is available at

The two projects discussed in this post demonstrate the efforts to address the two important aspects of progress in the uses of nanotechnology – understanding the health, safety, and environmental effects, and measuring the economic benefits of nanotechnology.

prod liab imageIt had to happen sooner or later.  And it’s happening now.  A coalition of nonprofit consumer safety and environmental groups brought an action on December 21 in federal district court in California against the Food and Drug Administration (FDA).  The action seeks an order for declaratory and injunctive relief under the Administrative Procedure Act to require the FDA to respond to a petition filed with the FDA in 2006 which sought action by the agency to assure the safety of the public exposed to nanomaterials, particularly sunscreen products.  The requested relief is detailed on pages 3-4 of the petition.  The lawsuit is International Center for Technology Assessment v. Hamburg (N.D. Calif., CV 11-6592).

The coalition includes the International Center for Technology Assessment (ICTA) as lead plaintiff for Friends of the Earth, Greenpeace, Food and Water Watch, the Center for Environmental Health, the Action Group on Erosion, Technology and Concentration (ETC Group), the Institute for Agricultural and Trade Policy, and several other groups.

Among other things, the petition detailed the status of research on and knowledge of the risks of nanomaterials, both relating to consumer products and the environment.  This information included studies that have indicated some of the ways that engineered nanoparticles may harm living cells through new channels of exposure.  Moreover, in 2007, the FDA’s own Nanotechnology Task Force issued a report recommending that the FDA issue guidance to manufacturers using nanomaterials and take steps to improve scientific knowledge of nanotechnology.

In the weeks to come, we will be anticipating the response from the FDA, which may very well insist that it has undertaken the efforts sought by the petitioners.  There are several other legal strategies that the FDA could employ, including claiming the lack of legal authority to put into place some or all of the relief sought in the petition or the need for interagency coordination.

The greatest significance of this lawsuit is that it puts nanotechnology into the courts.  This may be the first time, but it certainly won’t be the last time.

The 80-page petition is available at

The 2007 Nanotechnology Task Force report is available at

white-house-south-2007-djIn a June 9, 2011, memorandum to the heads of U.S. executive departments and agencies, entitled Policy Principles for the U.S. Decision-Making Concerning Regulation and Oversight of Applications of Nanotechnology and Nanomaterials, the White House confirmed its commitment to a “science-based” approach to health and safety matters related to nanotechnology.  The memorandum issued from the Office of Science and Technology Policy, the Office of Management and Budget, and the Office of the U.S. Trade Representative. The memorandum described its approach as

“generally applicable principles relevant to promoting a balanced, science-based approach to regulating nanomaterials and other applications of nanotechnology in a manner that protects human health, safety, and the environment without prejudging new technologies or creating unnecessary barriers to trade or hampering innovation.”

The memorandum went on to explain that the approach it establishes is inherent in the risk-based approach commonly used by federal agencies such as the FDA, but is grounded in best available, and evolving, science.

 This is a tall order.  It is important that the White House explicitly addressed nanotechnology and nanomaterials, rather than using the vague term “emerging technologies,” as it has done in the past.  But perhaps the most significant part of the memorandum is in its elevation of the science-based approach over other possible approaches (technology-based, economics-based, etc.) to the study and regulation of nanomaterials.

 Intending to provide guidance to existing federal agencies, the memorandum stated:  “Federal agencies should avoid making scientifically unfounded generalizations that categorically judge all applications of nanotechnology as intrinsically benign or harmful.”  Consumer trust, the memorandum went on to say, is important in encouraging technological innovation.

 On the one hand, the memorandum eased industry concerns that nanotechnology will be viewed as “bad” and all nanomaterials as “hazardous” because of the flurry of attention focused on the technologies and the concerns voiced by various groups.  But on the other hand, the message is clear that science will govern the study of nanomaterials and any decisions about whether or how to regulate.  And that is also a message to industry to come forward with the science that the agencies need.

 The memorandum also announced the creation of an interagency working group to coordinate this basic framework across agency lines, promote coordination of regulatory activities, and share information.

 How is this policy likely to play out in the relevant departments and agencies?  Here are a couple of recent steps that illustrate the initial approach:

 ●  On June 10, 2011, the FDA issued a Draft Guidance, Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, to provide manufacturers, suppliers, importers, and other stakeholders with the FDA’s “current thinking” on the subject.  The Draft Guidance was issued in conjunction with the White House memorandum.  The document provided no definitions, nor did it provide any information on the regulatory status of any products.  Rather, the document stated that its purpose is “to help industry and others identify when they should consider potential implications for regulatory status, safety, effectiveness, or public health impact that may arise with the application of nano-technology in FDA-regulated products.”

 The FDA Draft Guidance is available at

 ●  A similar document was issued by EPA setting forth its proposed policy for obtaining data on nanoscale materials in pesticides, pursuant to its authority under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).  Another important aspect of what EPA is considering is a case-by-case analysis of whether a nanoscale ingredient in a pesticide is considered “new” for the purpose of study and regulation.  This is a sharp departure from EPA’s earlier stance that it would consider all nanoscale ingredients as “new,” whether or not a non-nanoscale form of the ingredient was already registered under FIFRA.  The new approach is consistent with the urging of the White House memorandum that agencies avoid generalizations about nanomaterials and based all decision on the scientific evidence.

 The prepublication version of this notice is available at


The White House memo is available at

prod liab imageListening to the speakers at the American Bar Association section webinar on the subject of “Nano Governance:  The Current State of Federal, State, and International Regulation,” discussed in a recent blog post, I was struck by the proliferation of “alphabet soup” agencies and programs involved in deciding whether and how to regulate nanomaterials in the workplace, consumer products, and the environment.  The short list includes such well-known acronyms as FDA, EPA, OSHA, NIOSH, CPSC, NNI, TSCA, FIFRA, FHSA, REACH, and ISO (International Organization for Standardization), as well as many lesser known acronyms, such as SNUR (Significant New Use Rule), PPPA (Poison Prevention Packaging Act of 1970), CPSIA (Consumer Product Safety Improvement Act), OCSPP (EPA’s Office of Chemical Safety and Pollution Prevention), NMSP (Nanoscale Materials Stewardship Program), NICNAS (Australian National Industrial Chemicals Notification and Assessment Scheme), WPMN (international Working Party on Manufactured Nanomaterials), and many similar legislation and agencies on the state level.

The good news is that nanotechnology is receiving much attention across the board from regulatory agencies.  The less good news is that the work of determining the health and safety effects of nanomaterials on humans and the environment, including ecological systems, is fragmented and slow.

The U.S. federal government, by necessity, is comprised of a web of agencies and programs, each with many jobs.  With so much work to be done, smaller and smaller groups are focusing on specific research and problem solving initiatives.  As the federal government is accustomed to doing in many areas of concern, efforts to coordinate agencies and programs devoting a fraction of their time to nanotechnology health and safety issues are being utilized.  One clearinghouse for the efforts across the government is the National Nanotechnology Initiative (NNI).  Is that enough to prevent duplication of effort and resources and to encourage communication and progress?

The dilemma is not new.  It is at the foundation of all complex systems.  To get something done, the groundwork must be laid by a highly focused group.  As recommendations move along the regulatory channels, eventually (maybe) the work results in action by way of regulations or new/amended statutes.  Greater oversight and decision making at the top of the regulatory pyramid may sound more efficient, but the careful groundwork could be lost and the democratic principles on which our regulatory system is based (including publication and public comment) could be diminished.

Many of my posts have talked about the need for studies on the health, safety, and environmental effects of nanomaterials.  But it has been a long time since I raised the question of what these studies may mean for toxic tort litigation.  As in any litigation, the evidence, including scientific studies and the experts who interpret them, must be admissible under the relevant rules of evidence.  In the United States, there are two basic approaches to the admissibility of expert evidence in the courts – (1) the federal courts’ approach, which is governed by the Federal Rules of Evidence and a trio of cases beginning with Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993), and (2) the approach known as the Frye test.  Regardless of the approach used by the particular court considering the evidence, early studies that may demonstrate health or environmental risks associated with nanomaterials will have an uphill battle for admissibility in the courts.

Over the next month, I intend to discuss some of these issues in a series of posts.  This post will consider the first question:  What is it about this evidence that will be so difficult for the courts?

To begin with, let’s briefly look at the rules for admissibility of the evidence in court:

 1.  Frye Test:  This test derives from the case of Frye v. United States, 293 F. 1013 (D.C. Cir. 1923), a criminal case that involved a scientific lie-detection technique that was a sort of precursor to the modern lie-detector tests.  The court there said that “while courts will go a long way in admitting expert testimony deduced from a well-recognized scientific principle or discovery, the thing from which the deduction is made must be sufficiently established to have gained general acceptance in the particular field in which it belongs.”  Thus, courts view as admissible under this test only expert evidence derived from scientific studies or techniques in general use, and usually long-standing use, in the particular field, and which most experts in the field recognize as being reliable.

 2.  Daubert Test:  The Daubert case itself was a toxic tort, a prescription drug product liability action, so the Supreme Court had before it on the record scientific studies that resemble the kinds of studies of exposure-and-outcome that might be produced for nanomaterials.  The Supreme Court held that the test for admissibility of expert evidence under the Federal Rules is broader than the Frye test and requires that the proponent of the evidence demonstrate that it be reliable – i.e. that it be scientifically valid – and that it be relevant to a particular issue in the case, not that it merely be suggestive of health problems.  The Court emphasized that the trial judge is the “gatekeeper” who must make a determination at an early time in the litigation as to whether the expert evidence is admissible.  If it is not admissible, often plaintiffs’ cases are dismissed prior to trial.

 What evidentiary challenges will nanomaterial studies present?

 ●  The studies will provide only probabilistic evidence.  This means that the studies will only show statistical associations (probabilities) between exposure to a particular nanosubstance and a particular outcome (e.g. illness).  While the extent to which probabilistic evidence differs from traditional forms of proof in tort cases (such as motor vehicle accidents) is a matter of degree, the inability of the studies to confirm the causal relationship between exposure to a substance and the illness the plaintiff suffers will be problematic for plaintiffs’ cases.

 ●  The illnesses are likely to be “generic.”  Some substances previously studied are linked to “signature diseases,” which occur very rarely in the general population, but with greater frequency among people exposed to the substance.  Silicosis (silica dust), asbestosis (asbestos), and pleural mesothelioma (asbestos) are examples.  But most cancers, respiratory conditions, and neurological disorders, for example, are caused by a variety of triggers, some related to exposures, others genetic or idiopathic.  It is therefore difficult to differentiate those caused by a particular exposure and those arising for other reasons.

 ●  The nanostudies will be new.  Under either admissibility test, new and untested or unreplicated studies may not pass muster.  In toxic torts, history has shown that early plaintiffs may have considerable difficulty with the admissibility of their evidence; even if the evidence is ruled admissible, problems of proof arise because juries may not view the early evidence as having much weight.   As time goes on, these studies may gain more acceptance in the field – or, they may be proved to be aberrations.

 Next up:  Admissibility and scientific reliability of nanostudies.

Lab beakerThe New York Times recently published an article reviewing the state of research on the adverse health effects of the chemical bisphenol-A (known as BPA), which is found in plastic used for many consumer products.  BPA is a hot topic right now, both in the health and political arenas.  The reason is that BPA has been shown in some studies to mimic the hormone estrogen, which is considered an “endocrine disruptor” capable of causing harm to humans.  But whether BPA, in mimicking estrogen, actually causes harm has yet to be determined.

Some of the concerns about conducting and interpreting the health studies on BPA are instructive as we go forward with studies on the health effects of nanosubstances.

 Some particularly instructive observations in the article are:

 1.  Some scientists have noted the conflicting results in existing studies.  Some have suggested that the inconsistent results are, at least in part, a function of different laboratories studying the chemical in different ways:  “Animal strains, doses, methods of exposure and the results being measured – as crude as body weight or as delicate as gene expression in the brain – have all varied, making it difficult or impossible to reconcile the findings,” according to the article.

 2.  Even when experiments appear to be conducted identically, the interpretations may vary among scientists of different disciplines, using different standards.

 3.  In studying BPA and many other chemicals and substances (including nanosubstances), it is particularly important to be aware of the different ways the substance may act on adults, children, and fetuses exposed in utero.  Moreover, adverse impacts on fetuses include not just fetal development; a person born with fetal exposure could develop future exposure-related health problems during his or her lifetime.

 4.  Private laboratories tend to be the first to use new advances in research, while the government researchers tend to lag behind.  It is not clear which type is likely to yield the more accurate results – the new techniques or the tried-and-true techniques.

 In thinking about studying the health effects of nanotechnology-based substances, it is important to keep in mind these points.  Because nanosubstances are available for so many and varied uses, determining the actual health impacts will take time, money, and a coordinated effort among scientific disciplines.

Now is the time to move forward with just such a coordinated effort.

 The article on BPA is available at:



What do the Gulf oil spill, the attacks on the World Trade Center on September 11, 2001, and nanotechnology have in common?  On the surface, it would seem to be nothing.  But all three involve responses to potential health and environmental threats that are instructive about how we as a society respond to such threats.  Collectively, they raise some important issues regarding how our society views health and environmental risks in general.

 Don’t get me wrong.  In no way am I suggesting that nanotechnology is comparable to the disasters at Ground Zero or in the Gulf.  Rather, I am asking that you look at how government and funded research institutes manage long-term health and environmental effects that occur as a result of chronic low-dose exposures over time.  The potential health hazards of nanotechnology fall into the long-term category.  We don’t expect to see any acute health problems associated with nanotechnology, but we should be concerned about long-term exposures, and existing efforts to study the effects should be expanded.

 Let’s contrast what happens when there is a disaster.

 On August 19, 2010, administration officials reaffirmed their commitment to the recovery and restoration of the Gulf in the aftermath of the Deepwater Horizon oil rig explosion and the subsequent movement of oil into the waters and the ecosystems of the Gulf.  The media outlets have been full of video, photographs, and articles about the efforts of many organizations, companies, and governmental entities to clean up and minimize the potential harm to natural resources, the environment, and all forms of life.

 Not so long ago, something similar went on at Ground Zero in the aftermath of the collapse of the World Trade Center towers following the 9/11 terrorist attacks.  Early on, the focus of efforts at Ground Zero was on the search for survivors.  On September 29, the focus turned to recovery and cleanup, including removal of debris.  But even before that date, the federal, state, and local governments were engaged in managing the environmental disaster that resulted from the release of hazardous substances into the air, including asbestos, silica, lead, mercury, polycyclic aromatic hydrocarbons (PAHs), dioxin, polyvinyl chloride (PVC), Freon, and polychlorinated biphenyls (PCBs), to name a few.  Workers from FDNY, NYPD, Port Authority of New York and New Jersey, emergency medical personnel, and a host of volunteers worked at the site.

 It is easy to assign massive resources to the acute phase of a disaster, but much harder to sustain interest and funding as time goes on.  Eventually the media will move on to other stories now that the Macondo well is just about sealed, as it eventually did when the cleanup at Ground Zero was completed.  Funds have been established to make payments, lawsuits commenced.  But what lingers is the reality of long-term health effects that could emerge over time – ecosystem damage or cancer or other health risks.  Society has a certain myopia about such things.  Perhaps it is human nature to not want to think about the health problems that could arise years down the line.

 The protracted task of developing valid scientific studies on the health effects of any exposures, including nanoparticles, and interpreting the results is as essential as responding to the acute phase of a disaster.  Disasters like the Gulf spill and 9/11 suggest a kind of false dichotomy – that acute harms are more worthy of recognition in the law than chronic long-term harms.  The long-term harms may seem less urgent, but there is nevertheless an urgency about them as well.

 For example, following the Exxon Valdez oil spill in 1989, no concerted effort was made to assess the health effects of the cleanup on workers.  Years later, surveys told the story of respiratory and neurological illness.  This month, the National Institute of Environmental Health Sciences announced it would begin a study of the potential health effects of exposures of workers and residents as a result of the Gulf oil spill.  Even in the 9/11 context, where health screenings of Ground Zero responders have been ongoing since 2002, and a data base has been established, acceptable compensation has come nearly a decade after the disaster.  The law is slower to recognize the harms from chronic exposures, and slower to act to both compensate the injured and prevent further harm.  Clearly, some of this is a result of symptoms and other harms emerging over time.  But this is all the more reason to be vigilant and investigative from the start.

 Far from the spotlight of a high-profile disaster, and in the absence of a clearly exposed population to screen, studies on the health and environmental effects of exposures to substances about which we know little is essential.

 As mentioned, nanotechnology is not a disaster.  Far from it.  It is a means for creating better medical therapies, making some of our technology perform better, and offering consumers desirable features in everyday products such as textiles and cosmetics.  But this does not eliminate the need to make a concerted effort to study the long-term health and environmental effects of nanoparticles and nanomaterials.  No matter how long it takes; no matter how far out of the spotlight.

 For those interested in knowing more about the toxic aftermath of Ground Zero, see my article, Toxic Torts at Ground Zero, 39 ARIZ. ST. L.J. 383 (2007).

On the need for studies of the health impact of the Gulf spill, see

Gina M. Solomon & Sarah Janssen, Health Effects of the Gulf Oil Spill, J.A.M.A. (Aug. 16, 2010), available at



I recently came across a very interesting article that was written in the Summer of 2008, Nanoparticle-based Therapies in Humans: A Survey, available at The subject matter deals with medical therapies for humans that contain nanoparticles. The author explores the emerging area of medicine that incorporates nanotechnology to fill the gaps of traditional delivery systems (i.e. poor water solubility and lack of target specificity). In addition to gap filling, the therapies stand poised to take the medical field to a whole new level, and will pose a myriad of challenges for the FDA, the U.S. Patent and Trademark Office (PTO), and patent attorneys worldwide.

Some Broad Background:

It is important to understand why nanoparticles are responsible for the proliferation of a new way to deliver medicine to the ailing human body. Traditional delivery systems lack the specificity element and the medicine tends to be delivered in higher than necessary doses that could lead to possible toxic exposure to the patient. Also, the human body is a hostile environment which reduces the effectiveness of traditional drugs.

The author of the article pointed out the following benefits with regard to the developments in nanomedicine:

Nanoparticles are selected for properties such as biodegradability, biocompatibility, conjugation, complexation or encapsulation and their ability to be functionalized. There are two types of nanoparticle-based therapeutic formulation: (1) those where the therapeutic molecules are the nanoparticles (therapeutic functions as its own carrier); and (2) those where the therapeutic molecules are directly coupled (functionalized, entrapped or coated) to a carrier.

Another important and desirable property of nanoparticles is the “surface area effect” that occurs. As a particle’s size decreases, the number of atoms on its surface increases relative to those at the core. This results in an exponential increase in reactivity which equates to increased efficiency and effectiveness over larger molecule delivery systems.

Patents and Commercialization:

It is critical for a company to obtain valid patents if they have any hope to profit from the research and development efforts of producing a new drug delivery system. According to the author of the article I read, the current state of nanoparticle patents is confusing at best. He states, “the proliferation of nanoparticle patent applications filed at the PTO, coupled with the continued issuance of surprisingly broad patents by the PTO, is creating a chaotic, tangled patent landscape where competing players are unsure as to the validity and enforceability of numerous issued patents.”

In an earlier post, Nanobots, Patents, and Collaboration, I proposed that innovation through collaboration is likely the most ideal way to navigate in this emerging area of technology. It seems as though there is no clear guidance in light of the Bilski decision, other than the probability is high that broad patents will continue to issue (not a bad thing, but not helpful to those involved in developing the multilayered drug delivery systems). I find myself a bit conflicted because I am a proponent of patent protection, but I am a realist and understand that the smaller the technology goes, the more overlap that occurs between competing patents. Again, I assert that collaboration is key and I look forward to participating in the process.