Nanotechnology:
Regulatory Challenges

Presented at the FDA Nanotechnology Open Meeting

October 10, 2006

Bethesda, MD

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Definition of Nanotechnologies

• Size

  • ≤ 100nm

• Differential performance

  • Components organized on a nanometer-scale have significantly better/different performance than on a larger-scale

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Diversity of Nanotechnologies

• MEMS/NEMS

• Nanocrystals

  • API milling

  • Quantum Dots (CdSe)

• Nanotubes/Buckyballs (Cx)

• Nanowires

• Nanoparticles (metal, protein, etc.)

• Nanodroplets (micelles, PFC emulsions, etc.)

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Nanotech Safety Framework

• Non-nanotech composition

  • Safety, distribution of constituents in bulk

  • Existing drug/device guidance

• Nano-structure impact

  • Novel activity/reactivity

  • Biodistribution

  • Bioavailability

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Example: Kereos LTEs

• Ligand-Targeted Emulsions

  • "Oil-in-water" emulsions

  • Specific

    • Ligand "targets" the disease

    • Delivers payload to specific area

      • MRI: paramagnetic ion chelate

      • Therapeutic: paclitaxel

    • 10-100 ligands

    • ≈100,000 payload molecules

PFC

Targeting
Ligand

Gd-chelate

Lipid

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Example: Kereos LTEs

• Kereos "oil-in-water" emulsions

  • Specific

    • Ligand "targets" the disease

    • Delivers payload to specific area

      • MRI: paramagnetic ion chelate

      • Therapeutic: paclitaxel

    • 10-100 ligands

    • ≈100,000 payload molecules

Targeting
Ligand

Drug

PFC

Lipid

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• Non-nanotech composition

  • Safety, distribution of constituents in bulk

  • Liquid perfluorocarbon

    • Well-understood human safety as parenteral at higher doses

  • Paclitaxel

    • Extensive human safety experience, etc. as parenteral at higher doses

  • Gadolinium chelate

    • Several approved agents at much higher doses

  • Targeting ligand

    • NCE, small molecule RGD peptidomimetic

Example: Kereos LTEs

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• Non-nanotech composition

  • Existing drug/device guidance

    • Liposome guidance

    • Imaging guidance (3) (MRI agent)

    • Other guidance (therapeutic)

      • Non-clinical

      • Combination products

Example: Kereos LTEs

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• Nano-structure impact

  • Novel activity/reactivity

  • Biodistribution

    • Impact of targeting on PFOB and "payload" distribution

    • Differential clearance of Gd-chelate or paclitaxel vs. non-LTE

  • Bioavailability

Example: Kereos LTEs

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Conclusions

• Nanotechnology – broad umbrella

  • More useful as a word than as a classification

  • Argues against one-size-fits-all approach

• Safety considerations should be based on

  • Non-nanotech composition

    • Safety/toxicity of components

    • Appropriate existing drug/device guidance

  • Changes due to nanostructure