Cancer Nanotechnology:

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Cancer Nanotechnology New Opportunities for
Targeted Therapies
FDA Public Meeting October 10, 2006 Piotr
Grodzinski, Ph.D. Director, Nanotechnology for
Cancer Programs Office of Technology and
Industrial Relations National Cancer Institute
2
Nanotechnology-based Drug DeliveryKey Benefits

• Provides multi-functionality targeting,
  delivery, reporting
• Provides improved therapeutic index
• Provides lowered toxic side effects
• Delivers multiple drugs directly to tumor site
• Enables nucleic acid delivery
• Enables non-drug therapies (photothermal,
  photodynamic)

Nanomaterial characterization Responsible,
Systematic, Standardized
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Multi-Functional Nanoparticle-based Therapies

• Multi-functional platforms
• Targeting
• Delivery
• Reporting, biosensing

In one package Free drug formulations do not
possess multi-functional characteristics
First generation of nano-delivered drugs (no
targeting) approved by FDA Abraxane
M. Ferrari, Nature Reviews 5, 161 (2005)
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Nanoparticle-based Therapies Different
Approaches
Nanoshells Photothermal therapy
Dendrimers Targeted delivery of methotrexate
N. Halas, J. West et al, Ann Biomed Eng. 34, 15
(2006)
J. Baker, et al., Cancer Res. 65, 5317 (2005)
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Uncertainties of Moving Multi-Functional
Nanoparticles to the Clinic

• Differences exist between the development and
  regulatory pathway for multi-functional
  nanoparticles and traditional drugs and
  devices. Need to
• Define the classification (decision tree) in
  order to determine the characterization process
  ahead of the submission
• Provide interfaces within the regulatory agencies
• Establish uniform, publicly available guidelines
  for the investigators
• Determination if therapy is new when it uses an
  existing drug on a novel delivery platform is a
  challenge
• Gap exists between technology development in an
  academic setting and further technology
  maturation through clinical development and
  regulatory approval

6
NCI StrategyAlliance for Nanotechnology in
Cancer

• A comprehensive, systematized initiative
  encompassing the public and private sectors,
  designed to accelerate the use of the best
  capabilities of nanotechnology to cancer
  applications

• Centers of Cancer Nanotechnology Excellence
  (CCNEs) and Cancer Nanotechnology Platform
  Partnerships (CNPPs)
• To develop novel technologies to deliver drugs
  more effectively
• To develop new, highly sensitive and specific
  diagnostic techniques
• Nanotechnology Characterization Laboratory (NCL)
• To develop a standardized assay cascade for
  preclinical characterization
• To identify physical parameters and
  structure-activity relationships for
  biocompatibility
• Not to address animal efficacy, SAR, PK or PD
  studies, or manufacturing

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Nanoparticle Translation Mechanism From Early
Development to the Clinic

• Opportunities
• Leverage NCL capabilities
• Scale up the material manufacturing (GMP)
• Provide studies towards IND filing
• Initiate Phase 0/Phase I trials

• Challenges
• High cost
• Low interest in academic environment, where most
  of the innovation resides
• Partnerships with the industry needed

Next step
Nanotechnology Alliance, NCL
Adapted from Challenge and Opportunity on the
Critical Path to New Medical Products
(http//www.fda.gov/oc/initiatives/criticalpath/wh
itepaper.html)
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NanotechnologyEnvironmental and Safety
Considerations

• Hazard identification
• In vitro toxicity
• Acute in vivo toxicity
• Subchronic/chronic toxicity
• Route of exposure
• Dose response
• External dose
• Internal dose
• Biologically effective dose
• Exposure assessment
• Human exposure

• Nanomaterials
• production
• Chronic exposure
• of the worker
• Nanomaterials
• use for
• biomedical
• applications
• Preclinical studies

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Interagency Collaborations

• Standards/Precision Measurement Capabilities

• Characterization
• Critical path development
• Training

• Public Interface
• Interpret Data on Environment, Health and Safety

• Nanobiotechnology Training

• Shared Data and Platforms