Nanomaterials on Drug Products Katherine Tyner, PhD FDA/CDER/DARS - PowerPoint PPT Presentation

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

Diversity of Nanomaterials Makes regulatory activities complex Material Platform Route of Administration Sadrieh, N. 2012 Overview of CDER Experience with Nanotechnology-related Drugs. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM315773.pdf

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 • Surface charge • Particle size/size distribution • Surface chemistry • Agglomeration/aggregation • Zeta potential • Chemical composition • Surface energy • Crystal structure/crystallinity • Catalytic properties • Purity • Dustiness • Shape • Oleophilicity/hydrophilicity • Surface area • Grain size • Porosity • Photocatalytyic activity • Endotoxin content • Octanol-water partition • Solubility coefficient • Stability • Redox potential • Concentration • 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

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 Key Questions • • Look to regulations and guidances What are the challenges in when developing nanodrugs developing nano-drugs from manufacturing and regulatory (CMC) perspectives? • How are nano methods being • Manufacturing and characterization integrated into the drug techniques may be specific for manufacturing process? individual nano-drugs • What current limitations are • Consider all parts of a product’s encountered with today’s properties and design tests nanomaterials and how is the next accordingly 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