Considerations Regarding the Impact of Nanomaterials on Drug Products Katherine Tyner, PhD FDA/CDER/DARS January 14, 2013
Why Apply Nanotechnology to Drugs? Combination of size and surface effects novel properties Increase bioavailability Change biodistribution Increased drug action Stabilize easily degradable drugs Deliver drugs Targeted/controlled/smart delivery of API Multifunctional capabilities Liversidge GG & Cundy KC. International Journal of Pharmaceutics. 1995 125, 91-97
Sadrieh, N. 2012 Overview of CDER Experience with Nanotechnology-related Drugs. http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/advisorycommitteeforpharmaceuticalscienceandclinicalpharmacology/ucm315773.pdf Diversity of Nanomaterials Makes regulatory activities complex Material Platform Route of Administration
Considerations for Nano-Drug Formulations There is no FDA definition for nanotechnology or related terms Regulations and Law do NOT separate nanotechnology products All nano-drugs are treated on a case by case basis Look to regulations and guidances Part 314: Applications for FDA approval to market a new drug http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=314 Part 58: Good laboratory practices for nonclinical laboratory studies http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=58 Part 211: Current good manufacturing practices for finished pharmaceuticals http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=211 What are the common challenges in developing nanomedicines from manufacturing and regulatory (CMC) perspective?
Characterization of Nano-Drug Formulations 21 CFR 314.50(d) requires: Full description of physical and chemical characteristics and stability for the drug substance Identity Strength Quality Purity Potency Bioavailability http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=314&showfr=1&subpartnode=21:5.0.1.1.4.2
Suggested Minimal Characterization of Nanomaterials Particle size/size distribution Agglomeration/aggregation Chemical composition Crystal structure/crystallinity Purity Shape Surface area Porosity Endotoxin content Solubility Stability Concentration Surface charge Surface chemistry Zeta potential Surface energy Catalytic properties Dustiness Oleophilicity/hydrophilicity Grain size Photocatalytyic activity Octanol-water partition coefficient Redox potential Radical formation potential Card and Magnuson, J. Food Sci., 74, vi-vii, 2009; MinCHAR project; www.characterizationmatters.org http://www.toxicology.org/isot/ss/nano/docs/ostraat_guest_presentation.pdf
Characterization for Nano-Drug Formulations 21 CFR 314.50(d) requires: Full description of physical and chemical characteristics and stability for the drug substance Identity Strength Quality Purity Potency Bioavailability http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=314&showfr=1&subpartnode=21:5.0.1.1.4.2
p ph Considerations for Nano-Drugs Formulations Time --- Tyner KM et al Journal of Controlled Release. 95 (3) 501-514 (2004).
Session 2 Key Thoughts & Questions Key Thoughts Look to regulations and guidances when developing nanodrugs Key Questions What are the challenges in developing nano-drugs from manufacturing and regulatory (CMC) perspectives? Manufacturing and characterization techniques may be specific for individual nano-drugs How are nano methods being integrated into the drug manufacturing process? Consider all parts of a product s properties and design tests accordingly What current limitations are encountered with today s nanomaterials and how is the next generation of nano-products expected to address these limitations?
Session 2 Overview Analytical Considerations for the characterization of nanomaterial drug products Christie Sayes, PhD RTI International Panel discussion on manufacturing considerations for nanomaterials in drug products Marcus Brewster, PhD Janssen Research and Development Neil Desai, PhD Celgene Donna Cabral-Lilly, PhD Celator Pharmaceuticals Inc. Lawrence Tamarkin, PhD, CytImmune
Break out sessions A: Analytical methods used for the characterization of nanomaterials: limitations and need for additional research B: Current and emerging technologies for manufacturing stable nanomaterial containing drug products Each session will be run twice, and you are encouraged to attend each session Speakers and panelists will be participating in these session Time for extended discussion and Q & A