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FDA Taking Baby Steps Towards Regulating Nanotechnology

Posted Jun 13 2011 10:09pm

paradise_jordan_lg1 FDA Taking Baby Steps towards Regulating Nanotechnology

Jordan Paradise, J.D. [1]

[Ed. Note: HRW is pleased to welcome Seton Hall Law Professor Jordan Paradise, who researches and publishes on the legal, ethical, and societal implications of emerging science and technologies such as genetics and nanotechnology. She teaches Food & Drug Law, Administrative Law and Advanced Seminars in the field of Health & Technology. Professor Paradise has an article forthcoming in Volume 56 of St. Louis University Law Journal on the topic of FDA regulation of nanotechnology entitled Reassessing 'Safety' for Nanotechnology Combination Products: What Do 'Biosimilars' Add to Regulatory Challenges for the FDA? Her research and publications, including her forthcoming article, can be found at SSRN -- http://ssrn.com/author=512260 ]

On June 9, 2011, the Food and Drug Administration (FDA) released draft guidance for industry laying out the agency’s “current thinking on whether FDA-regulated products contain nanomaterials or otherwise involve the application of nanotechnology.” [2] The guidance urges that the document does not establish legally enforceable obligations, but should be viewed only as recommendations for industry.  It “does not establish regulatory definitions” or “address the regulatory status of products,” but does state that future additional guidance may be issued for specific product or classes of products.  Published concurrently with an announcement on policy principles for nanotechnology regulation from the Office of Science and Technology Policy, [3] the draft guidance exemplifies the ongoing battle by federal administrative agencies to quantify, categorize, and regulate nanotechnology.

Carbon nanotubes (courtesy, National Science Foundation). The properties of CNTs are being explored for applications in electronics, photonics, multifunctional fabrics, biology (e.g., as a scaffold to grow bone cells), and communications. See a 2009 Discovery Magazine article [http://discovermagazine.com/2009/jul-aug/09-ways-carbon-nanotubes-just-might-rock-world] for other examples

Carbon nanotubes (courtesy, National Science Foundation). The properties of CNTs are being explored for applications in electronics, photonics, multifunctional fabrics, biology (e.g., as a scaffold to grow bone cells), and communications. For other examples see a 2009 Discovery Magazine article, http://discovermagazine.com/2009/jul-aug/09-ways-carbon-nanotubes-just-might-rock-world

Framed as two general “Points to Consider” applicable to both new products and any manufacturing changes to FDA-approved and cleared products, the draft guidance provides both a dimensional aspect “whether an engineered material or end product has at least one dimension in the nanoscale range (approximately 1nm to 100 nm)” and a behavioral aspect “whether an engineered material or end product exhibits properties or phenomena, including psychical or chemical properties or biological effects, that are attributable to its dimensions, even if these dimensions fall outside the nanoscale range, up to one micrometer.”  Notably, the second point expands the first dimensional aspect beyond the 100 nm range if the properties exhibited are tied directly to its dimensions up to one micrometer (also called a micron).  (One nanometer is equal to 10-9 meters (a sheet of paper is about 100,000 nanometers thick)); one micrometer/micron is equal to 10-6 meters.)

Supporting its two points, the guidance also provides the agency’s “Rationale for Elements within the Points to Consider.”  These largely recite the current state of knowledge of nanoscale properties and phenomena as the underpinnings of the two points.   Specifically, the FDA distinguishes the “deliberate manipulation and control of particle size” of an engineered material or end product from the natural functioning at the nanoscale, identifies the traditional bounds of the nanoscale encompassing 1nm to 100nm as serving merely as “a first dimensional reference point” for industry, highlights the relationship between size and physical and chemical properties as important for questions of safety and efficacy, and explains the broadening of dimensions of “nanoscale” up to one micrometer as linking to the use of agglomerates and aggregates that may coat or functionalize a product.

Scanning electron microscope image of a single lung cancer cell (H1650) captured on the slide of a micropost. (http://www.nano.gov/sites/default/files/pointofcontactmicrochipforearlydetectionofcancercells.pdf)

Scanning electron microscope image of a single lung cancer cell (H1650) captured on the slide of a micropost. (http://www.nano.gov/sites/default/files/pointofcontactmicrochipforearlydetectionofcancercells.pdf)

While couched as a “first step” by the FDA, the draft guidance reflects an incremental and coordinated effort among various FDA Centers, including the Center for Drug Evaluation and Research (CDER), the Center for Biologics Research and Evaluation, the Center for Devices and Radiological Health, and the Center for Food Safety and Nutrition on issues with nanotechnology products.  Nearly four years ago, the FDA’s multi-center Nanotechnology Task Force [4] published a report [5] acknowledging that future advancements in nanotechnology may pose challenges for the existing FDA oversight structure.  Rapidly developing nanoscale [6] applications were identified as integrating mechanical, chemical, electrical, and optical properties in novel and dynamic ways:

The very nature of nanoscale materials their dynamic quality as the size of nanoscale features change, for example, and their potential for diverse applications may permit the development of highly integrated combinations of drugs, biological products, and/or devices, having multiple types of uses, such as combined diagnostic and therapeutic intended uses.  As a consequence, the adequacy of the current paradigm for selecting regulatory pathways for “combination products” may need to be assessed to ensure predictable determinations of the most appropriate pathway for such highly integrated combination products. [7]

A nanosensor probe carrying a laser beam (blue) penetrates a living cell to detect the presence of a product indicating that the cell has been exposed to a cancer-causing substance.

A nanosensor probe carrying a laser beam (blue) penetrates a living cell to detect the presence of a product indicating that the cell has been exposed to a cancer-causing substance.

Infused with public and private investments, nanotechnology-based research and development is now burgeoning.  The cumulative federal investment in nanoscale science and engineering research and development through the National Nanotechnology Initiative (NNI) over the last decade has reached nearly $14 billion ; [8] the 2011 NNI budget provides $1.76 billion spread across 15 federal agencies . [9] The unique and far-ranging properties of nanostructures and nanotechnology have particularly facilitated breakthroughs in the pharmaceutical and medical device realms.  The interface of nanotechnology and biotechnology have increased bioavailability, introduced more targeted drug delivery and release, decreased adverse side effects, and enabled cutting-edge cancer treatments.  Current projections place the “nanomedicine” market at $53 billion in 2011. [10]

Following its 2007 report, the FDA has taken a number of internal steps aimed at nanotechnology in addition to the recent guidance.  FDA’s CDER and the Research Office of Pharmaceutical Science issued an internal Manual of Policies and Procedures (MaPP) in May 2010 that instructs drug reviewers to capture “relevant information about nanomaterial-containing drugs” that will be entered into a nanotechnology database. [11] The MaPP states that “in order to develop guidance for industry, CDER needs to organize all the data submitted in support of nanotechnology-based drug applications,” [12] gather all “relevant information about nanomaterial-containing drugs” and enter them into a nanotechnology database maintained by the agency. [13] While imposing no additional requirements on drug applicants, it signals recognition from the FDA of the nascent state of understanding of the complex scientific implications in human drugs.

nanostructured zein forming sub-micron size tubes, http://www.nano.gov/sites/default/files/zeinnanofabricatedbiomaterials_usda.pdf

nanostructured zein forming sub-micron size tubes, http://www.nano.gov/sites/default/files/zeinnanofabricatedbiomaterials_usda.pdf

FDA has also held several public meetings to gather nano-specific information: in October 2006 to aid  the Task Force Report; [14] in September 2008 to assist the agency in implementing recommendations  laid out in the Task Force Report; [15] and in September 2010 to solicit data and information on biocompatibility assessment of diagnostics and devices that include nanomaterials. [16] The FDA also maintains materials for the public on its webpage regarding nanotechnology. [17]

FDA is also partnering with the National Cancer Institute’s Nanotechnology Characterization Laboratory and the National Institute of Standards and Technology to conduct “preclinical efficacy and toxicity testing of nanoparticles” in an effort to identify appropriate standards for molecular-sized cancer drugs. [18] The FDA has identified risk characterization based on physical and chemical properties, in vitro and in vivo models to assist in predictions of human response to exposure, quantification methods, measures of adsorption and transport, and relationships between nanomaterial properties and the human body in terms of uptake via the skin, lungs, and gastrointestinal tract as specific areas of interest. [19]

Although moving slowly, the FDA is moving forward on issues of nanotechnology.  Stay tuned…

[1] Prof. Paradise has an article forthcoming in Volume 56 of St. Louis University Law Journal on the topic of FDA regulation of nanotechnology entitled Reassessing ‘Safety’ for Nanotechnology Combination Products: What Do ‘Biosimilars’ Add to Regulatory Challenges for the FDA? Her research and publications, including her forthcoming article, can be found at SSRN http://ssrn.com/author=512260

[2] FDA Draft Guidance for Industry, Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, June 9, 2011, available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm For more information, see also FDA Draft Guidance Questions and Answers, June 9, 2011, available at http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ucm258391.htm ; Jeffrey Ventura, FDA Press Release, FDA takes ‘first step’ toward greater regulatory certainty around nanotechnology, June 9, 2011, available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm258377.htm

[3] Office of Science and Technology Policy, Office of Management and Budget, and the United States Trade Representative, Policy Principles for the U.S. Decision-making Concerning Regulation and Oversight of Applications of Nanotechnology and Nanomaterials, June 9, 2011, available at http://www.whitehouse.gov/sites/default/files/omb/inforeg/for-agencies/nanotechnology-regulation-and-oversight-principles.pdf

[4] Press Release, Food and Drug Administration, FDA Forms Internal Nanotechnology Task Force (Aug. 9, 2006), available at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4241B1-02-33-FDA-Nano%20FDA%20News%20release.pdf .

[5] Food and Drug Administration Nanotechnology Task Force, Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology Task Force (2007), p. 20-21, available at http://www.fda.gov/nanotechnology/taskforce/report2007.pdf .

[6] The nanoscale is traditionally measured as under 100nm (or 10-9m, or one billionth of a meter).   The National Nanotechnology Initiative (NNI) defines “nanotechnology” as involving three inter-related (and inseparable) aspects: “1) [r]esearch and technology development at the atomic, molecular or macromolecular levels, in the length scale of approximately 1-100 nanometer range; 2) creating and using structures, devices and systems that have novel properties and functions because of their small and/ or intermediate size; and 3) ability to control or manipulate at the atomic scale.”  Environmental Protection Agency, Nanotechnology: An EPA Research Perspective (June 2007), http://nepis.epa.gov/Adobe/PDF/P1003H7X.PDF

[7] Id.

[8] Office of Science and Technology Policy, NNI Strategic Plan 2010; Request for Information, 75 Fed. Reg. 38,850-53, 38,850 (2010).

[9] National Nanotechnology Initiative, About the NNI Funding, http://www.nano.gov/initiatives

[10] Raj Bawa & Summer Johnson, The Ethical Dimensions of Nanomedicine, 91 Med. Clinics N. Am. 881-87, 882 (2007), citing Nanotechnology in Healthcare (Cleveland: Freedonia Group 2007).

[11] Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Science, MaPP 5015.9 Reporting Format for Nanotechnology-Related Information in CMC Review (effective date June 3, 2010), available at http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/UCM214304.pdf.

[12] Id. at 2.

[13] Id.

[14] Planning of Public Meeting, Regulated Products Containing Nanotechnology Materials, 71 Fed. Reg. 155, 46,232-33 (Aug. 11, 2006).

[15] Public Meeting, Consideration of FDA-Regulated Products That May Contain Nanoscale Materials, 73 Fed. Reg. 153, 46,022-24 (Aug. 7, 2008).

[16] Public Workshop on Medical Devices and Nanotechnology: Manufacturing, Characterization, and Biocompatibility Considerations, 75 Fed. Reg. 162 (Aug. 23, 2010).

[17] Food and Drug Administration, Nanotechnology, http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/default.htm

[18] See National Cancer Institute, Nanotechnology Characterization Lab, http://ncl.cancer.gov/

[19] Food and Drug Administration, 2010 FDA Research Project Categories, http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ucm196697.htm

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