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Update on Nanotechnology Activities in CDER and FDA

Keith O. Webber, Ph.D.Deputy Director

OPS/CDER/FDA

ACPS MeetingTuesday, July 22, 2008

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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

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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 (?)

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polymeric biodegradable nanoparticlesceramic (inorganic) nanoparticlespolymeric micelles (amphililic block copolymers)liposomesdendrimersnanocrystals (Quantum dots) for diagnostics applications and imagingmagnetic 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)

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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

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Evaluating Nanotechnology Products

Product quality assessment studies Characterization Quality control Manufacturing

Product safety assessment studies Biodistribution Clearance Metabolism Toxicology

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CDER Nanotechnology Products

Sunscreens Nanoscale TiO2 and ZnO

Reformulations of previously approved products Nanoemulsions Nanocrystal colloid dispersions

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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

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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.

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Identification of Products Containing Nanomaterials

Recommendation: Issue guidance recommending that

sponsors identify particle size of small particle materials in FDA-regulated products

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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

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Labeling

Recommendation

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

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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

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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.

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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

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CDER Nanotechnology Initiatives: Future Plans

Develop a definition, if deemed necessary

Identification of areas that require guidance development

Development of guidance documents, if needed.

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Today’s Presentations

Larry Tamarkin (CytImmune Sciences)

Stephen Ruddy (Elan Corp.)

Darin Furgeson (Univ. of Wisconsin)

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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?