1. ACPS October 20061 Nanotechnology: Issues and Future Directions Nakissa Sadrieh Ph.D. OPS/CDER/FDA

2. ACPS October 20062 Outline Introduction (Nakissa Sadrieh, FDA) Applicability of existing regulations to the development of a dendrimer nanotechnology-based pharmaceutical (Jeremy Paull, Starpharma) Nanotechnology in emerging medical and consumer products-Opportunities and risks (Russel Lebovitz, Suma Partners) Questions to the ACPS (Nakissa Sadrieh, FDA)

3. ACPS October 20063 Why is there interest in nanotechnology? At the nanoscale, the physical, chemical, and biological properties of materials differ in fundamental and valuable ways from the properties of individual atoms and molecules or bulk matter. Nanotechnology R&D is directed toward understanding and creating improved materials and systems that exploit these new properties.

4. ACPS October 20064 Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale. NNI Definition

5. ACPS October 20065 Applications of Nanoparticles to Drug Discovery and Biology Fluorescent biological markers Detection of proteins Probing of DNA structures Separation and purification of biological molecules and cells MRI contrast enhancement Tumor destruction via heating Tissue engineering Drug and gene delivery (Nanomarkets, March 2005)

6. ACPS October 20066 Trends in Development of Nanoparticles in Medicine Currently, nanoparticle applications in medicine are geared towards drug discovery and drug delivery. In the future, the goal is to make the nanoparticles multifunctional and controllable by external signals or local environments.

7. ACPS October 20067 Possible Opportunities for Nanotechnology in Drug Delivery Enhanced drug properties such as: Solubility Rate of dissolution Oral bioavailability Targeting ability Enhanced dosing requirements: Lower dosed administered Better side effect profile More convenient dosage forms

8. ACPS October 20068 FDA-Regulated Products Expected to be Impacted by Nanotechnology Drugs (novel NMEs or delivery systems) Medical devices Biotechnology products Tissue engineering products Vaccines Cosmetics Combination products

9. ACPS October 20069 Examples of Nanotechnology Combination Product Multi-component system that may consist of: Carrier/delivery system (drug or device) Therapeutic agent (drug or biologic) Imaging agent Targeting agent Implantable microchip-based delivery systems that deliver different drugs under controlled conditions. Injectable delivery systems (transdermal microneedles). (Nanomarkets, March 2005)

10. ACPS October 200610 Are nanomaterials new to FDA? Drugs: Imaging agents (Gadolinium MRI contrast agents, iron oxide contrast agent). Reformulated drugs using nanocrystal technology to enhance bioavailability properties of previously approved drugs (immunosuppressant, antiemitic). Liposomal products Nanoparticle-based formulation of previously approved anti-tumor agent

11. ACPS October 200611 Other “nano-scale” products on the market Devices Silver nanoparticles (anti-bacterial wound dressing) Engineered Calcium Phosphate (duplicates microstructure, composition and performance of human bone) Nanoparticle dental restorative Cosmetics (“nanosomes”) Sunscreens (TiO2 and ZnO)

12. ACPS October 200612 FDA Activities in Nanotechnology Nanotechnology interest group within the Office of the Commissioner. Working groups within individual Centers. Internal nanotechnology task force established by the acting Commissioner. Public meeting in October 2006 to understand developments in nanotechnology. MOU between FDA, NCI and NIST. Research

13. ACPS October 200613 Current approach Specific consideration may need to be given to nanoparticle-containing products, in the areas of: Characterization Safety

14. ACPS October 200614 Current thinking within CDER nanotechnology working group CDER/FDA’s current requirements for safety testing of products is very rigorous. However if research identifies toxicological risks that are unique to nanomaterials, additional testing requirements may become necessary. At this time, there are no testing requirements that are specific to nanotechnology products.

15. ACPS October 200615 What about a Nanotechnology Product Guidance Document? Guidances are built on precedence from review and on extensive literature data. Because nanotechnology is an evolving field and we are still learning, CDER is not anticipating any new preclinical or CMC guidance documents regarding nanomaterials in the near future.

16. ACPS October 200616 Review Process for Nanotechnology Drugs The effectiveness of the agency’s regulatory approach to meet unique challenges that may be presented by the use of nanotechnology materials in FDA-regulated products is currently being evaluated. However, in the meantime, and based on the available information, the review process for products containing nanomaterials is likely to essentially remain the same as that used for products that do not contain nanomaterials.