US FDA Food Nanotechnology Guidelines: Where we are What is next. October 5, 2011

Transcription

1 US FDA Food Nanotechnology Guidelines: Where we are What is next October 5, 2011

2 Overall FDA Approach (to date) Legal authorities apply no worse for nano than they do for other food regulatory categories (food additive, GRAS, dietary supplements) Can ask the right questions where allowed, or infer the same level of protection for industry self assessment No indication that nano-scale in food is more hazardous than non-nano-scale First step: collect data where manufacturing for effect causes size variation in submicron range Specific exposure/toxicity guidance will come with understanding that follows

3 Guidance so far has been 1. When nano-characteristics data are needed Chemistry guidance that does not say nano 2. When FDA is likely to ask nano-specific questions Reviewer s Guidance (Manual of Policies and Procedures) FDA-wide no definition guidance 3. What are the boundaries of new authorization required or come talk to us. Regulatory category specific started with Dietary Supplements

4 Context 2007 FDA Nanotechnology Task Force Report US Government-wide Policy (July 2011 version) EPA Guidance and Rulemaking in Progress

5 2007 FDA Nanotechnology Task Force Report Bottom Lines Nanoscale materials present challenges similar to other emerging technologies The fact that safety and efficacy can vary with size can complicate the challenges Not apparent that nanoscale materials as a group would have more inherent hazard than other materials as a group Need to better inform FDA reviewers and industry about what is known and expected for analysis of nanoscale materials in products. 5

6 The fact that safety and efficacy can vary with size can complicate the challenges Size or particle-surface related impurity What to test in maximum tolerated dose studies to inform low dose risk

7 What to test? The typical nanomaterial is a mixture of distributions Composition Size Aspect ratio %Coating Pb As Hg Se Fe Sb yy xx Surface adherents

8 Transformations will change the distributions that make up the nanomaterial mixture. Neat source material in toxicity study in food container How do we know we are studying the right material distributions in toxicity studies? released to food Released in gut

9 Tracking potency? choose wisely What causes the external dose of a given nanomaterial to be toxic? How do you track it? For example, for benzene, it s the benzene you follow from release to receptor. For a metal oxide nano-object it could be a functional assay, or uncoated surface area, or coated area, or rutile vs anatase crystal fraction, or size for a certain morphology, or something else. anatase rutile TiO 2

10 US Government-wide Context Emerging Technology Policy Coordinating group: existing regulatory statutes provide a firm foundation for the regulation and oversight of nanomaterials; in particular these statutes address a range of potential applications for the technology. Federal agencies should avoid making scientifically unfounded generalizations that categorically judge all applications of nanotechnology as intrinsically benign or harmful. Federal agencies will strive to provide their stakeholders with clear information that delineates the specific risks identified and the context in which they arise.

11 US Environment Protection Agency Issuing a testing rule under new chemicals authority for specific nanomaterials Has developed a size-based rationale for requiring information in pesticide registrations Policy describes agency discretion to include and exclude materials for the nano requirements. For example, Silver and Carbon Nanotubes are in clay and proteins are out

12 US government-wide trend to use submicron feature size as a gateway question, but regulate for specific categories of materials.

13 FDA Guidance in Place Chemistry specifications 2007 Food Contact Notifications 2009 Food Additive Petitions 2009 Color Additive Petitions Routine updates, no public comment period offered, no mention of nano (stealth nano guidance) Requires data if function is related to size

14 The Chemistry Guidance Language 2007 Food Contact Notifications Guidance update Physical/Chemical Specifications. In cases where particle size is important to achieving the technical effect or may relate to toxicity, sponsors should describe particle size, size distribution, and morphology, as well as any size-dependent properties. Intended Chemical Effect. If technical effect is dependent on particle size, sponsors should present data that demonstrate the specific properties of the particles that make them useful for food-contact applications.

15 2009 Direct Food Additive and Color Additive Petitions Guidance updates If the particle size is important for the (color) additive to achieve its intended technical effect, such that the (color) additive is produced or processed using techniques or tools that manipulate the particle size and may contain altered particles that are formed as manufacturing by-products, data on the size (average and distribution), shape, surface area (average and distribution), surface charge (zeta potential), and morphology of the particles, as well as any other sizedependent properties (e.g., agglomeration, aggregation, dispersion) should be included, as appropriate.

16 atoryinformation/ucm htm dancedocuments/foodingredientsandpackaging/ucm htm dancedocuments/foodingredientsandpackaging/ucm htm

17 Data on Size-related Purity 2009 Direct Food Additive Petitions Guidance update (continued) Specifications for Identity and Purity Parameters related to the particle size, shape, and surface properties of the food additive, as appropriate, if particle size is important for the identity and functionality of the additive.

18 What does impurity mean for a nanomaterial when size or shape or surface coating determines properties? size size size 100% within range 50% within range 50% impurity? 10% within range 90% impurity? 18

19 More Data Collection: FDA Reviewer Guidance Center for Drug Evaluation and Research and Center for Veterinary Medicine: Manual of Policies and Procedures Policy for where FDA reviewers should populate an internal FDA database on nanomaterials in products No additional manufacturer reporting requirements The 1 micron upper limit was begun here Internal pressure for Center for Food Safety to adopt similar procedures. nualofpoliciesprocedures/ucm pdf

20 Next Step: Clarify Regulatory Status Boundaries Phase 1: 2011 FDA-wide Guidance (Draft) Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology Guidance for Industry

21 The FDA not a definition when considering whether an FDA-regulated product involves the application of nanotechnology, FDA will ask: Whether (the product) has at least one dimension in the nanoscale range (approximately 1 nm to 100 nm); or exhibits properties or phenomena attributable to its dimension(s), even if..up to one micrometer. These considerations apply not only to new products, but also may apply when manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components.

22 No specific exclusion for solubility No exclusion of organics, biomolecules Does include already authorized products when manufacturing is changed to affect function, and that change affects feature size in the submicron range.

23 FDA is not focusing on definitions of nanomaterial to create new product reviews, rather, they are focusing on when new manufacturing (nanotechnology, even if it is not called that) creates new properties and therefore a new product.

24 A Hint of What s to Come This guidance document does not establish any regulatory definitions. Rather, it is intended 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 nanotechnology in FDA-regulated products.

25 First in a series of regulatory definitions? Dietary Supplements July 2011 Draft Guidance for Public Comment cuments/dietarysupplements/ucm htm#iii-scope

26 Dietary Supplements a change in the manufacturing process for a NDI* intended to produce particles in the 1 nm to 100 nm (approximate) nanoscale range may alter the chemical properties of the NDI. If so, the resulting ingredient with different chemical properties would likely not be covered under an existing notification for a related substance manufactured without using nanotechnology and, therefore, would likely require a NDI notification. Manufacturers planning a manufacturing change are encouraged to consult with FDA on any questions as to whether such a change would be viewed as having created a different NDI. *New Dietary Ingredient

27 Similar Guidance in Final Review for Food Additives and for Colors Drafts focus on when a change in manufacturing would change regulatory status such that a new notification or authorization would be reguired. Colors has more regarding data types to submit due to lesser pre-submission guidance currently out for colors.

28 Under Consideration at FDA Red book toxicity testing guidance Specific testing and characterization methods

29 FDA Recommends Regulatory Science Research for Nano FDA encourages promotion of, and participation in, regulatory science research and other efforts to increase scientific understanding, to facilitate assessment of data needs for regulated products. Such activities should, where appropriate, be coordinated with and leveraged against activities supported by other Federal agencies, the private sector, or other international regulatory counterparts.

30 FDA Research Categories for Nano Physico-Chemical Characterization improved methods and tools to detect and measure Nonclinical Modeling assays and models to assess safety and/or efficacy Risk Characterization to enhance the understanding of hazard identification, exposure science, and risk modeling. Risk Assessment development of generalized class-based approaches to risk assessment Risk Communication

31 What is needed to clarify engineered nano in food from food that is nano Agree to methods-based definitions for what is new nano after ph 2 transition in stomach Then agree to how to characterize persistent particles in gut, so they can be tested or related to pristine nano toxicity test data ILSI RF s NanoRelease project

32 Thank you