Nanotechnology: risk governance

Transcription

1 Roundtable on Risk Governance Policy for Nanotechnology (OECD) Vienna (Austria), September 25th (2009) Nanotechnology: risk governance looking at medicines / nanopharmaceuticals regulation as an example Rogério Gaspar rgaspar@ff.ul.pt /

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3 Where does nanotechnology belong in the map of science? Alan L. Porter and Jan Youtie, Nature Nanotechnology, (September 2009): The position of nanoscience and nanotechnology over a base map of science. Each node in this map15 is one of the 175 subject categories in the SCI. The size of each node is proportional to the number of nanopapers published in journals in each subject category during the period January July Location on the axes in this Kamada Kawai algorithm representation has no inherent meaning: the connecting arcs and proximity reflect similarity based on cross-citation patterns, reinforced by colouring to reflect the clustering of subject categories into macrodisciplines

4 Where does nanotechnology belong in the map of science? Alan L. Porter and Jan Youtie, Nature Nanotechnology, (September 2009):

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6 Target Discovery, Drug Design & Development Common Issues

7 Genetically engineered mouse models in cancer drug development

8 Toxicology profiling in Drug Discovery Kramer et al 2007, NRDD, 6:

9 Reduction in the number of candidate survivors after clinical phase

10 Challenges in Pharma R&D business development

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12 Trends in value chain and payment strategies

13 Lab to clinic: overall trends ( ) Pharma 2020: The vision, PriceWaterhouseCoopers, 2007

14 Nanopharmaceuticals: overall view of particulate carriers

15 Cancer 15

16 R. Duncan, Nature Reviews Cancer, September imed.ul Research Institute for Medicines and Pharmaceutical Sciences imed.ul Cancer, EPR and Intracellular trafficking

17 Common Technical Document and MAA requirements Quality Drug Substance Medicinal product Non Clinical Toxicity (acute, long term) Carcinogenesis Toxicokinetics Pharmacokinetics Clinical Efficacy Disease progression Clinical Safety Therapeutic indication

18 R. Gaspar and R. Duncan, Adv Drug Delivery Reviews, 2009

19 Current gaps and how to fill them Areas impacted by nanomaterial-containing products Product quality assessment studies Characterization Quality control Manufacturing Product safety assessment studies Biodistribution Clearance Metabolism Toxicology

20 Current gaps and how to fill them Characterisation needs Development of appropriate tools and methodologies to Adequately assess product chemistry and unique characteristics of product (complete formulation) Enhance quality control measures Produce consistent formulations with low batch-to-batch variability Link product quality to performance

21 Current gaps and how to fill them Examples of features to analyse Size Primary particle size Aggregation/agglomeration state 2D and 3 D distribution Particle size distribution Chemical composition Element identification and distribution Crystal form Surface composition; surface charge Reactivity

22 Current gaps and how to fill them Current Preclinical Tests for Safety Evaluation of Drugs Include Pharmacology Safety pharmacology Toxicology (including clinical pathology and histopathologic analysis) (A)DME Genotoxicity Developmental toxicity Immunotoxicity Carcinogenicity Other

23 Biocompatibility versus toxicity R. Gaspar and R. Duncan, Adv Drug Delivery Reviews, 2009

24 R. Gaspar and R. Duncan, Adv Drug Delivery Reviews, 2009

25 R. Gaspar and R. Duncan, Adv Drug Delivery Reviews, 2009

26 Biological properties R. Gaspar and R. Duncan, Adv Drug Delivery Reviews, 2009

27 Current gaps and how to fill them Safety considerations Do nanopharmaceuticals gain access to tissues and cells normally bypassed by larger particles? If so, What effects do they have on cellular and tissue functions (transient and/or permanent)? How long do they remain there? How are they cleared from tissues and blood?

28 Carbon nanotubes toxicology A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice, M.L. SCHIPPER, N.NAKAYAMA-RATCHFORD, C. R. DAVIS, N. W. S. KAM, P. CHU, Z. LIU, X. SUN, H. DAI AND S. S. GAMBHIR, nature nanotechnology VOL 3 APRIL 2008

29 Cytosolic delivery (strategies for improved cancer therapy and nucleic acid delivery) Watson et al., Adv. Drug Deliv. Rev. 57(2005): Nishikawa et al., Adv. Drug Deliv. Rev. 57(2005):

30 Current gaps and how to fill them (A)DME Considerations What are differences in the (A)DME profile, for nanopharmaceuticals versus larger particles of the same drug? Are there methods for measuring levels of nanopharmaceuticals in blood and tissues? Limit of detection, distinction between nanopharmaceuticals and aggregates or between intact nanopharmaceutiacls and metabolized nanopharmaceuticals Accuracy of mass balance studies, for drugs administered at very low levels or targeted products? How is clearance of targeted nanopharmaceuticals accurately assessed? How are nanopharmaceuticals appropriately labeled for (A)DME studies?

31 Nano-Imaging PET CT (Gemini) X-ray MR (cath lab) WIP SPECT CT WIP X-ray - CT Intera Achieva I/T Cardiovascular X-ray MR (mobile C-arm) 31

32 Diagnostics & Therapeutics

33 Roundtable on Risk Governance Policy Group 1 : for Nanotechnology What are the criteria used to decide that risk management actions are required? How is scientific evidence and uncertainty reflected in subsequent risk management actions? How are decisions taken? - and how transparent and predictable are they? To what extent is risk management science-based?

34 Moving forward building bridges into the future!

35 Pharmacological Sciences Nanomedicine & & DDS Molecular & Cell Biology of Eukaryotic Systems Lisbon approach to 3Ds: imed.ul Neuron, Glia Biology in Health and Disease Metabolism & Genetics Medicinal Chemistry Chemical Biology Toxicology 35

36 (amastigotes/500 nuclei) x liver weigth x 2x105 1 Oncology & Inflamation Liposomes Nanoparticles Polymeric Ther. NANOMEDICINE & Drug Delivery Systems Coordination Rogério Gaspar Projects Infectious Diseases Liposomes Nanoparticles Vaccines Dermal Research Pulmonary Delivery and macromolecular complexation Therapeutic activity 300 of Trifluralin Liposomes Negative P ositive Liposomal Control 1 Control 2 (Sb) TFL 3 Basic/Applied Research Team National & International Colaborations 4 technicians 7 PhD students 14 PhD 2 Research fellows 2 MSc students 36

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