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The AAPS Journal

, Volume 17, Issue 1, pp 44–64 | Cite as

Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks

  • Jeremy A. Bartlett
  • Marcus Brewster
  • Paul Brown
  • Donna Cabral-Lilly
  • Celia N. CruzEmail author
  • Raymond David
  • W. Mark Eickhoff
  • Sabine Haubenreisser
  • Abigail Jacobs
  • Frank Malinoski
  • Elaine Morefield
  • Ritu Nalubola
  • Robert K. Prud’homme
  • Nakissa Sadrieh
  • Christie M. Sayes
  • Hripsime Shahbazian
  • Nanda Subbarao
  • Lawrence Tamarkin
  • Katherine Tyner
  • Rajendra Uppoor
  • Margaret Whittaker-Caulk
  • William Zamboni
Meeting Report Theme: Nanotechnology in Drug Development
Part of the following topical collections:
  1. Theme: Nanotechnology in Drug Development

Abstract

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 WORDS

nanomaterials nanomedicine nanotechnology PQRI risk management USFDA 

Abbreviations

AAPS

American Association of Pharmaceutical Scientists

ADME

absorption, distribution, metabolism, and excretion

AES

atomic emission spectroscopy

API

active pharmaceutical ingredient

ASMF

active substance masterfile

ASTM

American Society for Testing and Materials

AUC

area under the curve

BCS

Biopharmaceutical Classification System

CDER

Center for Drug Evaluation and Research (at USFDA)

CE

Conformité Européenne

CFR

Code of Federal Regulations (United States)

CFSAN

Center for Food Safety and Applied Nutrition (at USFDA)

cGMP

current good manufacturing practices

CHMP

Committee for Medicinal Products for Human Use (at EMA)

CIOMS

Council for International Organizations of Medicinal Sciences

CMC

chemistry, manufacturing, and controls

CQAs

critical quality attributes

CV

coefficient of variance

DLS

dynamic light scattering

DMF

drug master file

DSTS

Drug Submission Tracking System (Health Canada)

EDQM

European Directorate for the Quality of Medicines & Healthcare

EDS

energy dispersive X-ray spectroscopy

EM

electron microscope

EMA

European Medicines Agency

EU

European Union

GRAS

generally recognized as safe

HPFB

Health Canada’s Health Products and Food Branch

ICCR

International Cooperation on Cosmetic Regulation

ICH

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

ICP

inductively coupled plasma

IEP

isoelectric point

IND

Investigational New Drug application

ISO

International Organization for Standardization

ITF

Innovation Task Force (at EMA)

IV

intravenous

L

liter

μg

micrograms

MPS

mononuclear phagocyte system

NCI

National Cancer Institute

NDA

New Drug Application

NGO

nongovernmental organization

nm

nanometer

NP

nanoparticle

NTA

nanoparticle tracking analysis

OECD

Organization for Economic Co-operation and Development

PD

pharmacodynamics

PEG

polyethylene glycol

PK

pharmacokinetics

PLD

PEGylated liposomal doxorubicin

PQRI

Product Quality Research Institute

QbD

quality by design

R&D

research and development

RCC

Canada-US Regulatory Cooperation Council

RES

reticuloendothelial system

SME

small- or medium-sized enterprise (EMA)

SUPAC

scale-up and post-approval changes

TGA

Therapeutic Goods Administration (Australia)

TNF

tumor necrosis factor alpha

TPCC

Therapeutic Products Classification Committee (at Health Canada)

USFDA

United States Food and Drug Administration

USP

United States Pharmacopeia

WPMN

Working Party on Manufactured Nanomaterials (at the OECD)

Notes

Acknowledgments

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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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Jeremy A. Bartlett
    • 1
  • Marcus Brewster
    • 2
  • Paul Brown
    • 3
  • Donna Cabral-Lilly
    • 4
  • Celia N. Cruz
    • 3
    • 5
    Email author
  • Raymond David
    • 6
  • W. Mark Eickhoff
    • 7
  • Sabine Haubenreisser
    • 8
  • Abigail Jacobs
    • 3
  • Frank Malinoski
    • 9
  • Elaine Morefield
    • 10
  • Ritu Nalubola
    • 11
  • Robert K. Prud’homme
    • 12
  • Nakissa Sadrieh
    • 13
  • Christie M. Sayes
    • 14
  • Hripsime Shahbazian
    • 15
  • Nanda Subbarao
    • 16
  • Lawrence Tamarkin
    • 17
  • Katherine Tyner
    • 3
  • Rajendra Uppoor
    • 3
  • Margaret Whittaker-Caulk
    • 3
  • William Zamboni
    • 18
    • 19
  1. 1.PfizerGroton LaboratoriesGrotonUSA
  2. 2.Janssen Pharmaceutica, Johnson and JohnsonBeerseBelgium
  3. 3.Center for Drug Evaluation and ResearchUnited States Food and Drug AdministrationSilver SpringUSA
  4. 4.Celator Pharmaceuticals, Inc.EwingUSA
  5. 5.United States Food and Drug AdministrationSilver SpringUSA
  6. 6.BASF CorporationEcology and SafetyFlorham ParkUSA
  7. 7.Merck and Co.West PointUSA
  8. 8.European Medicines AgencyLondonUK
  9. 9.Nanomedicines AllianceWashingtonUSA
  10. 10.Vertex Pharmaceuticals IncorporatedBostonUSA
  11. 11.Office of the CommissionerUnited States Food and Drug AdministrationSilver SpringUSA
  12. 12.Chemical and Biological Engineering, School of Engineering and Applied SciencePrinceton UniversityPrincetonUSA
  13. 13.Center for Food Safety and Applied NutritionUnited States Food and Drug AdministrationSilver SpringUSA
  14. 14.RTI InternationalResearch Triangle ParkUSA
  15. 15.Health Canada, Health Protection BranchOttawaCanada
  16. 16.Biologics Consulting GroupAlexandriaUSA
  17. 17.CytImmuneRockvilleUSA
  18. 18.UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology ExcellenceUniversity of North CarolinaChapel HillUSA
  19. 19.Wildcat Pharmaceutical Development CenterHoustonUSA

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