Nanotechnology Lawyer & Attorney : Porter Wright Morris & Arthur : Nanotechnology Law Report - Germanium nanobead image provided by UT-Battelle, which manages Oak Ridge National Laboratory for the Department of Energy

Product-Specific Questions to be Discussed at Nanotechnology Public Meeting: (taken from FDA website)

BREAKOUT SESSION: Medical devices, including diagnostics (discussion will include combination products)

1. Are there general parameters or screening tools by which to evaluate the likelihood that a particular material might have nanoscale-specific properties and to decide when and what sort of further evaluation might be warranted? Are there characteristics and properties of materials that FDA can use to broadly categorize materials with respect to their likelihood of having nanoscale-specific properties warranting further review?
2. What data and information should be considered in determining whether the presence of a nanoscale version of material in an existing device could affect the device's regulatory status, for example, in determining whether that device remains substantially equivalent to a predicate device?
3. Do the existing Quality System Regulation requirements for process validation adequately address issues for manufacturing nanotechnology products, including issues related to demonstrating batch-to-batch reproducibility?
   (Product classification/combination product question)
4. Do you believe that nanoscale products or products that contain nanoscale materials raise any novel questions relevant to their classification as biological products, devices, drugs, or combination products?  For instance, if an article achieves "its primary intended purposes through chemical action within or on the body of man or other animals" or is "dependent upon being metabolized for the achievement of its primary intended purposes," it can be a "drug" (including a drug constituent part of a combination product) but cannot be a "device" (including a device constituent part) (21 USC 321(h), 21 CFR 3.2). Do you believe that any nanoscale therapeutic articles, including constituent parts of combination products, interact with the body in ways that raise novel questions for determining whether the interaction should be viewed as a chemical action, as the article's being metabolized, or as some other form of interaction? Please provide examples to illustrate your views.

BREAKOUT SESSION: Prescription drugs, including biological, animal and over-the-counter (OTC) drugs (May include sunscreen)

1. Are there general parameters or screening tools by which to evaluate the likelihood that a particular material might have nanoscale-specific properties and to decide when and what sort of further evaluation might be warranted? Are there characteristics and properties of materials that FDA can use to broadly categorize materials with respect to their likelihood of having nanoscale-specific properties warranting further review?
2. What are the unique manufacturing features of products containing nanoscale materials and how should these be evaluated?
   • Is the manufacturing process understanding and development for nanoscale materials different from that of conventional drugs?
   • Does the use of nanoscale materials affect scale-up? If so, how?
   • If you develop a nanoscale material-containing product under the Quality by Design (QbD) paradigm, does this contribute to process understanding and manufacturing capabilities?
   • Can nanoscale materials affect product formulation, components, excipients, and processing?
3. What are unique physicochemical attributes of products containing nanoscale materials?
   • How do they impact controls, standards, specifications, etc.?
   • How do they affect characteristics and performance of a product?
   • How do they complicate development and manufacturing of these products?
4. What has been your experience to date with products containing nanoscale materials and/or have you avoided these products due to concerns about development, characterization, and manufacturing?
5. What additional questions focusing on characterization and manufacturing aspects of products containing nanoscale materials should be addressed in this forum or brought to the attention of CDER?

BREAKOUT SESSION: Food and color additives, including food contact substances

1. Can you identify specific classes of food ingredients or packaging components derived from or incorporating nanotechnology that you would identify as raising or not raising unique safety concerns and why?
2. In your experience, what analytical methods and tools have proven to be of the most use to you in characterizing nanoscale materials? Looking to the future, can you suggest methods that might be developed or refined to augment those methods currently used?
3. What physical characteristics of food-related nanoscale materials are of greatest concern regarding the safety of dietary consumption?
4. Nanoscale food ingredients and food packaging may behave differently than macroscale materials. For example, nanoscale materials may agglomerate in food, interact with other components of the food matrix, and interact in the human body following ingestion. What methods are you using to characterize nanoscale materials in the food matrix and in the human body following ingestion?
5. Are the current FDA Redbook toxicological endpoints and array of toxicity tests used for assessing the safety of macroscale food ingredients and packaging components sufficient to describe the toxicity of their nanoscale counterparts, or must new endpoints and assays be considered? Are you aware of any other toxicity tests not presently in wide use that may be more suitable? Are there toxicity tests that could be used to bridge data on macroscale ingredients to their nanoscale counterparts?
6. Is nanotechnology applied to food ingredient and food packaging production primarily to create new effects for such compounds or to enhance existing effects? What are the perceived impacts on regulatory status or good manufacturing practice in each of these scenarios?
7. How can FDA better communicate issues of regulatory status and safety of food ingredients and packaging components derived from nanotechnology to the public and industry?

BREAKOUT SESSION: Dietary supplements

1. What data are there on whether nanoscale versions of common low solubility salts of dietary ingredients have new properties or characteristics?
2. Would additional absorption, distribution, or safety data be needed to demonstrate the safety of a nanoscale version of an existing dietary ingredient?
3. What data and information should be considered in determining whether a nanoscale version of an existing dietary ingredient is a new dietary ingredient?

BREAKOUT SESSION: Cosmetics

1. What characteristics or types of nanoscale materials would be important to specify when considering potential risks of cosmetic products.
2. If your company markets a cosmetic product with nanoscale particles, what function do they perform, at what concentration are they used, and how stable are they in the formulation?
3. What, if any, additional studies are done for a product containing nanoscale particles to prove that this type of formulation is safe? What differences in safety or absorption have you observed between products formulated with nanoscale particles versus those that are formulated with [macroparticles] non-nanoscale materials?
4. Are safety assessments being done at the bulk ingredient level or final formulation or both? How do these assessments differ?
5. What is the effect on bioavailability of making larger particles nanoscale? Would you expect to see increased absorption/toxicity?

The primary disagreement appears to be whether to issue a policy at all, or rely on existing statutory and regulatory controls.  As one might expect, the panel was split on this issue, resulting in no action in the short term.  The split was right down the middle with 5 panel members voting in favor of a policy, 5 voting against, and 1 abstaining.

The panel did agree that FDA should collaborate with OSHA and EPA should either agency begin drafting a policy concerning nanoparticles.  FDA will hold a public meeting in September to discuss particle size in drugs and how to obtain such information from its current database.

FDA's inaction is not wholly surprising given the state of nanotechnology regulation.  However, the even split was somewhat unexpected.  The debate seems to center around the data submissions by companies seek FDA approval on products and what is already required.  I, personally, would not have thought the division would be so even (unless purposefully manufactured).  Perhaps this is a mircochasm of the public generally, that being a 50/50 split on what the next step should be?  Or perhaps this is administrative gridlock in an election year?  Or perhaps this is simply an administrative agency continuing to act deliberately in considering the nanotechnology question?

Throughout the report, the author addresses the unique, and in some cases, not so unique, concerns raised by using nanomaterials in food packaging, all through the use of hypothetical applications.  The purpose of the report is to "tee-up" the regulatory issues faced by the FDA, as the primary regulatory agency in charge of food packaging, and the EPA as a secondary regulating authority.  The report provided a broad based look at the issues raised by this specific nanomaterial application.

Like other areas of potential regulation, the use of nanomaterials in such close proximity to food raises its own concerns and potential.  Beyond the discussion raised by the paper itself, which are absolutely worth considering, it is encouraging to see the GMA involved in this study.  Because of the number of regulatory topics that are emerging, and each one seemingly unique to its own industry of application, it becomes critical for stakeholders to involve themselves in the debate.