Ricardo Carvajal Hyman, Phelps & McNamara, P.C. hpm fdalawblog

1. FDA’s Regulation of Products Derived Through Nanotechnology: Controversies and Potential Impacts on Nanomedicine 3rd Annual Unither Nanomedical & Telemedical Technology Conference February 2010 Ricardo Carvajal Hyman, Phelps & McNamara, P.C. www.hpm.com www.fdalawblog.net

2. International Government Investment Japan Others U.S. W. Europe Source: PCAST/NSF

3. National Nanotechnology Initiative • A government program established in 2001 to coordinate federal nanotech R&D • 25 agencies participate, including FDA • More than $1.5 billion has been allocated to 13 agencies

4. NNI Funding, 2001 - 2010 • FDA funding? • EHS funding?

5. FDA’s Nanotechnology Task Force Report • FDA’s Nanotechnology Task Force established in 2006 • Public meeting and comment solicitation in 2006 • Report was issued in 2007, but FDA considers the report to be current

6. Nanotech Task Force Report: Scientific Capacity • FDA’s scientific capacity needs to be improved. • Adequacy of tools needed to describe and evaluate nanomaterials should be assessed. • Lack of data on nanomaterial safety is a problem. • Early consultation with the agency is highly recommended, especially for combination products.

7. Nanotech Task Force Report: adequacy of FDA’s authority • Existing statutory authority is “generally adequate” to address risks • Nanotech-specific regulations are unwarranted. • Authority is “more comprehensive” for products subject to premarket authorization

8. Nanotech Task Force Report: recommendations for guidance • FDA should issue guidance that addresses submission of additional data, potential effects on regulatory pathways, additional steps needed to address safety or quality issues. • A chicken and egg problem?

9. FDA Science and Mission at Risk • Report of the Subcommittee on Science and Technology • Prepared for FDA Science Board, November 2007 • FDA cannot fulfill its mission because: • scientific base has eroded and scientific organizational structure is weak • scientific workforce does not have sufficient capacity and capability • IT infrastructure is inadequate

10. How does FDA regulate nanotechnology? • No regulatory definition • Risk-based approach that focuses on products, not processes • Insufficient scientific basis to conclude that, as a class, products derived through nanotechnology pose greater human health risks • A familiar tension – the need to minimize regulatory burdens, consistent with need to protect public health

11. Courtesy Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy

12. FDA’s flexible regulatory scheme Identity? Intended use?

13. A word about combination products • Primary mode of action governs assignment: which mode of action makes the greatest contribution to the overall intended therapeutic effects? • Tiebreaker: which center has experience or expertise with safety and effectiveness questions presented? • One center takes the lead, but consults with others. • Both formal and informal determinations of jurisdiction are available.

14. Drug Approval Process CDER Handbook

15. “Post-market oversight” doesn’t mean “no authority” • FDA has authority to take unsafe products off the market. • Flow of information – premarket v. post-market

16. Examples: products on the market • Drug: Abraxane, paclitaxel in an albumin nanosphere, cancer • Device: NanoOss, nanocrystalline hydroxyapatite, bone void filler • Cosmetic: Hydra Zen, nanoencapsulated triceramides, moisturizing cream • Dietary supplement: NanO Bio-Sim, nanosized diatomaceous earth, immune system support • Food packaging w/silver nanoparticles, antimicrobial

17. In some sectors, a rush to market? • Hundreds of “nanotech” cosmetic and dietary supplement products” have sped to market. • Project on Emerging Nanotechnologies (PEN) inventory

18. Been there, done that...

19. Sunscreen: safety concerns? • FDA started rulemaking on the sunscreen OTC monograph in 1978. • 1993 – proposed tentative final monograph. • 1999 – issued final monograph, effective in two years. • 2001 – final monograph was stayed. • 2007 – proposed amendment of final monograph.

20. In the interim, enforcement discretion • FDA policy: no action against OTC products until review is complete unless product poses a potential health hazard to the consumer. • FDA, 1999: “micronized titanium dioxide” is not a new ingredient, but is instead a specific grade of titanium dioxide for which there is no evidence of a safety concern.

21. ICTA citizen petition • International Center for Technology Assessment petitioned FDA to amend the sunscreen monograph to address engineered nanoparticles • Manufacturers of sunscreens that contain nanoengineered titanium dioxide or zinc oxide should be required to file new drug applications. • Marketing should be prohibited, and all products recalled. • Strange question: is nanotechnology safe to slather on our children?

22. To label or not to label? • Product labeling cannot be misleading • Has a material fact been omitted with respect to consequences that could result from use of the product?

23. How much milk can a dairy cow yield?

24. rbST, a bioengineered animal drug • Approved in 1994, rbST is a bioengineered hormone given to cattle to increase milk production. • FDA’s approval was challenged administratively and judicially – FDA won. • FDA also won in rejecting mandatory labeling. • rbST foes want voluntary labeling; rbST advocates contend that labeling is false or misleading. • Human safety? Animal safety? Effect on small farms?

25. ... our yoghurt is made with fresh cow’s milk that is free of any artificial growth hormones. Look for the “No artificial growth hormones” announcement on our lid. It means the yoghurt inside is rbST-free ...

26. The rbST labeling battle continues, state by state • FDA is unlikely to expend resources on issues where there is no clear impact on public health. • Advocates on both sides have turned to the states.

27. The danger of a vacuum at the top • Local restrictions on nano are already coming into play, e.g., Berkeley. • California has issued call for data on carbon nanotubes. • Zeal for regulation tempered by desire to attract/retain high-tech incubators?

28. McKinsey & Co., February 2009

29. The essentials • Safety • Benefits • Choice • Effective, transparent, predictable regulation

30. Reported nanosafety practices in research laboratories worldwide • Francisco Balas, Manuel Arruebo, Jone Urrutia & Jesus Santamaria, Nature Nanotechnology 5, 93 - 96 (2010) • “[M]ost researchers do not use suitable personal and laboratory protection equipment when handling nanomaterials that could become airborne.” • “One of the most surprising results is that nearly three quarters of respondents reported not having internal rules to follow regarding the handling of nanomaterials.”

31. Thank you! Ricardo Carvajal Hyman, Phelps & McNamara, P.C. www.hpm.com

32. NIH Nanomedicine Roadmap Initiative • Phase I - gather information about chemical and physical properties of nanoscale biological structures (2005-2010) • Phase II – apply knowledge and tools to treating

33. NIH Nanomedicine Development Centers • Nanomedicine for Nucleoprotein Machines • Phi26 DNA-Packaging Motor for Nanomedicine • Center for Cell Control • NDC for the Optical Control of Biological Function • Center for Protein Folding Machinery • National Center for Design of Biomimetric Nanoconductors • Engineering Cellular Control: Synthetic Signaling and Motility Systems • Nanomedicine Center for Mechanobiology Directing the Immune Response

34. European Technology Platform (ETP) on Nanomedicine • Initiative led by industry, set up with the European Commission – industrial and academic experts • “it has become increasingly clear to the industrial sector that an academic driven or laissez faire approach to nanomedicine will be an inefficient process” • Research agenda • Nanotechnology-based diagnostics including imaging • targeted drug delivery and release • regenerative medicine