1. 1 Update on Nanotechnology Activities in CDER and FDA Keith O. Webber, Ph.D. Deputy Director OPS/CDER/FDA ACPS Meeting Tuesday, July 22, 2008

2. 2 Purpose of this Session  Update the ACPS on CDER’s nanotechnology-related activities  Familiarize the committee with some pharmaceutically-relevant nanotechnology concerns  Receive advice from the ACPS on the regulation of nanotechnology drugs

3. 3 Outline  Background Nanoparticles in drug products Impact on product evaluation in CDER  FDA Nanotechnology Task Force Report Summary Recommendations Public Meetings  CDER initiatives Development of database of products Research MaPP (?) Guidance (?)

4. 4 polymeric biodegradable nanoparticles ceramic (inorganic) nanoparticles polymeric micelles (amphililic block copolymers) liposomes dendrimers nanocrystals (Quantum dots) for diagnostics applications and imaging magnetic nanoparticles (iron oxide for MRI) Nanoscale materials of potential use in drugs Sahoo and Labhasetwar, DDT, 2003  polymeric biodegradable nanoparticles  ceramic (inorganic) nanoparticles  polymeric micelles  Liposomes  Dendrimers  nanocrystals (Quantum dots) for diagnostics applications and imaging  magnetic nanoparticles (iron oxide for MRI)

5. 5 Potential Pharmaceutical Applications of Nanotechnology  Targeted therapies Increase delivery to site of action Decrease systemic exposure  Multifunctional particles  Novel dosage forms Transdermal delivery Carrier function Controlled or sustained release  Protection of drug from degradation  Enhanced bioavailability

6. 6 Evaluating Nanotechnology Products  Product quality assessment studies Characterization Quality control Manufacturing  Product safety assessment studies Biodistribution Clearance Metabolism Toxicology

7. 7 CDER Nanotechnology Products  Sunscreens Nanoscale TiO2 and ZnO  Reformulations of previously approved products Nanoemulsions Nanocrystal colloid dispersions

8. 8 The FDA Nanotechnology Task Force Focus:  Enable development of safe and effective products  Address knowledge or policy gaps  Guide science and technology  Assess current state of science  Strengthen collaboration with federal agencies

9. 9 Task Force Report: Bottom Lines 1. Nanoscale materials could be used in most types of products regulated by FDA. 2. Nanoscale materials present challenges similar to other emerging technologies. 3. The fact that safety and efficacy can vary with size adds an additional level of complexity. 4. It is not apparent that nanoscale materials, as a group, have more inherent hazard than other materials. 5. Steps should be taken to better inform FDA reviewers and industry about what is known, needed, and expected.

10. 10 Identification of Products Containing Nanomaterials Recommendation:  Issue guidance recommending that sponsors identify particle size of small particle materials in FDA-regulated products

11. 11 Product Safety and Effectiveness Recommendations  Issue calls for safety and effectiveness data  Issue guidance on Manufacturing GRAS (“generally recognized as safe”) food ingredients Food and color additives Devices Cosmetics Dietary supplements

12. 12 Labeling Recommendation Address on a product-by-product basis whether labeling must or may contain information on the use of nanomaterials

13. 13 Public Meetings  Nanotechnology Materials in FDA- Regulated Products (October 2006)  Alliance for NanoHealth (March 2008)  FDA-wide meeting (September 2008) Focus on center-specific issues CDER will focus mainly on characterization, instrumentation, and manufacturing

14. 14 CDER Nanotechnology Initiatives: Policy  Develop a database of drugs To identify data gaps (e.g., particle size information) Tracking  Develop a MaPP to capture relevant information in reviews.

15. 15  Collaborators: NIST, NCL/NCI, CDRH  Dermal penetration of nanoparticles in sunscreens in minipigs.  Characterization of nanoparticles in marketed sunscreens (to address Citizen Petition).  Toxicity of select nanoparticles; correlation of in vitro findings with in vivo results. CDER Nanotechnology Initiatives: Research

16. 16 CDER Nanotechnology Initiatives: Future Plans  Develop a definition, if deemed necessary  Identification of areas that require guidance development  Development of guidance documents, if needed.

17. 17 Today’s Presentations  Larry Tamarkin (CytImmune Sciences)  Stephen Ruddy (Elan Corp.)  Darin Furgeson (Univ. of Wisconsin)

18. 18 Questions for the Committee  Is specific CDER guidance needed for the development of nanotechnology derived drug applications?  If guidance is needed from CDER, what areas should these guidances focus on?  For regulatory purposes, what elements or factors should CDER consider incorporating into a definition of nanotechnology?