Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks
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At the Product Quality Research Institute (PQRI) Workshop held last January 14–15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.
KEY WORDSnanomaterials nanomedicine nanotechnology PQRI risk management USFDA
American Association of Pharmaceutical Scientists
absorption, distribution, metabolism, and excretion
atomic emission spectroscopy
active pharmaceutical ingredient
active substance masterfile
American Society for Testing and Materials
area under the curve
Biopharmaceutical Classification System
Center for Drug Evaluation and Research (at USFDA)
Code of Federal Regulations (United States)
Center for Food Safety and Applied Nutrition (at USFDA)
current good manufacturing practices
Committee for Medicinal Products for Human Use (at EMA)
Council for International Organizations of Medicinal Sciences
chemistry, manufacturing, and controls
critical quality attributes
coefficient of variance
dynamic light scattering
drug master file
Drug Submission Tracking System (Health Canada)
European Directorate for the Quality of Medicines & Healthcare
energy dispersive X-ray spectroscopy
European Medicines Agency
generally recognized as safe
Health Canada’s Health Products and Food Branch
International Cooperation on Cosmetic Regulation
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
inductively coupled plasma
Investigational New Drug application
International Organization for Standardization
Innovation Task Force (at EMA)
mononuclear phagocyte system
National Cancer Institute
New Drug Application
nanoparticle tracking analysis
Organization for Economic Co-operation and Development
PEGylated liposomal doxorubicin
Product Quality Research Institute
quality by design
research and development
Canada-US Regulatory Cooperation Council
small- or medium-sized enterprise (EMA)
scale-up and post-approval changes
Therapeutic Goods Administration (Australia)
tumor necrosis factor alpha
Therapeutic Products Classification Committee (at Health Canada)
United States Food and Drug Administration
United States Pharmacopeia
Working Party on Manufactured Nanomaterials (at the OECD)
The authors would like to thank Don Henry from USFDA and Vicky Penn from PQRI for their organization efforts on this workshop. The authors would also like to thank Drs. Susan Ciotti and Stephen Gracon, NanoBio Corporation, for their presentation on nanoemulsions, which is the basis for the topical case study discussed in this paper. The authors would also like to thank Professor Marisa Papaluca-Amati and Dr. Falk Ehmann, both from the EMA, Scientific Support, for their remote participation in the Q&A session on the “EMA Perspective on the Development of Nanomedicines.”
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