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

  • Meeting Report
  • Theme: Nanotechnology in Drug Development
  • Published:
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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.

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Notes

  1. A recently published PQRI White Paper (98) on this same topic outlines the best practices assessing scale-up and post-approval changes for drug products developed and approved using enhanced approaches.

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)

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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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Authors and Affiliations

  1. Pfizer, Groton Laboratories, Groton, Connecticut, 06340, USA

    Jeremy A. Bartlett

  2. Janssen Pharmaceutica, Johnson and Johnson, Beerse, Belgium

    Marcus Brewster

  3. Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20903, USA

    Paul Brown, Celia N. Cruz, Abigail Jacobs, Katherine Tyner, Rajendra Uppoor & Margaret Whittaker-Caulk

  4. Celator Pharmaceuticals, Inc., Ewing, New Jersey, 08628, USA

    Donna Cabral-Lilly

  5. United States Food and Drug Administration, 10903 New Hampshire Ave., Rm. 4142 Bldg. 51, Silver Spring, Maryland, 20993, USA

    Celia N. Cruz

  6. BASF Corporation, Ecology and Safety, Florham Park, New Jersey, 07932, USA

    Raymond David

  7. Merck and Co., West Point, Pennsylvania, 19486, USA

    W. Mark Eickhoff

  8. European Medicines Agency, Canary Wharf, London, E14 5EU, UK

    Sabine Haubenreisser

  9. Nanomedicines Alliance, Washington, District of Columbia, USA

    Frank Malinoski

  10. Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, 02210, USA

    Elaine Morefield

  11. Office of the Commissioner, United States Food and Drug Administration, Silver Spring, Maryland, 20903, USA

    Ritu Nalubola

  12. Chemical and Biological Engineering, School of Engineering and Applied Science, Princeton University, Princeton, New Jersey, 08544, USA

    Robert K. Prud’homme

  13. Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, Silver Spring, Maryland, 20903, USA

    Nakissa Sadrieh

  14. RTI International, Research Triangle Park, North Carolina, 27709, USA

    Christie M. Sayes

  15. Health Canada, Health Protection Branch, Ottawa, Ontario, Canada

    Hripsime Shahbazian

  16. Biologics Consulting Group, Alexandria, Virginia, 22314, USA

    Nanda Subbarao

  17. CytImmune, Rockville, Maryland, 20850, USA

    Lawrence Tamarkin

  18. UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina, Chapel Hill, North Carolina, 27514, USA

    William Zamboni

  19. Wildcat Pharmaceutical Development Center, Houston, Texas, 77389, USA

    William Zamboni

Authors
  1. Jeremy A. Bartlett
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  2. Marcus Brewster
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  3. Paul Brown
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  5. Celia N. Cruz
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  15. Christie M. Sayes
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  17. Nanda Subbarao
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  18. Lawrence Tamarkin
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  19. Katherine Tyner
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  20. Rajendra Uppoor
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  21. Margaret Whittaker-Caulk
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  22. William Zamboni
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Corresponding author

Correspondence to Celia N. Cruz.

Additional information

Guest Editors: Nakissa Sadrieh and Banu Zolnik

The authors wish to dedicate this manuscript to the memory of our colleague, Dr. Marcus Brewster, for his great contributions to the advancement of nanotechnology in drug products.

The workshop was cosponsored by USFDA, USP, and AAPS and endorsed by the Society of Toxicology.

Dr. Marcus Brewster passed away before the completion of this report.

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Bartlett, J.A., Brewster, M., Brown, P. et al. Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks. AAPS J 17, 44–64 (2015). https://doi.org/10.1208/s12248-014-9701-9

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