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. Cruz; 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

doi:10.1208/s12248-014-9701-9

The AAPS Journal

January 2015, Volume 17, Issue 1, pp 44–64

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

Authors
Authors and affiliations

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

First Online:: 25 November 2014

Received:: 25 August 2014
Accepted:: 08 November 2014

9 Citations
560 Downloads

Part of the following topical collections:

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)

References

1.
PQRI Workshop: Nanomaterial in Drug Products Current Experience and Risk Management. January 14–15, 2014, USP Meeting Center, Rockville, MD. Final Program Agenda at: http://www.pqri.org/workshops/Nanomaterials2013/Final.Program.Agenda.pdf. Accessed 21 Aug 2014.
2.
Cruz CN, Tyner KM, Velezquez L, Hyams K, Jacobs A, Shaw A, et al. CDER risk assessment exercise to evaluate potential risks from the use of nanomaterials in drug products. AAPS J. 2013;15(3):623–8. doi:10.1208/s12248-013-9466-6.CrossRefPubMedCentralPubMedGoogle Scholar
3.
FDA’s approach to regulation of nanotechnology products. Available online at: http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ucm301114.htm; see also Hamburg, 2012. Science 336:299–300. Accessed 21 Aug 2014.
4.
Office of Science and Technology Policy, Office of Management and Budget, and the United States Trade Representative. Principles for regulation and oversight of emerging technologies, March 11, 2011; available online at: http://www.whitehouse.gov/sites/default/files/omb/inforeg/for-agencies/Principles-for-Regulation-and-Oversight-of-Emerging-Technologies-new.pdf. Accessed 21 Aug 2014.
5.
Office of Science and Technology Policy, Office of Management and Budget, and the United States Trade Representative. Policy principles for the U.S. decision-making concerning regulation and oversight of applications of nanotechnology and nanomaterials, June 9, 2011; available online at: http://www.whitehouse.gov/sites/default/files/omb/inforeg/for-agencies/nanotechnology-regulation-and-oversight-principles.pdf. Accessed 21 Aug 2014.
6.
Final guidance for industry: considering whether an FDA-regulated product involves the application of nanotechnology, June 2014. Available online at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM401695.pdf. Accessed 21 Aug 2014.
7.
FDA guidance on nanotechnology, issued June 2014; Available online at: http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/default.htm. Accessed 05 Nov 2014.
8.
FDA’s nanotechnology regulatory science research plan (accessible at: http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ucm273325.htm. Accessed 21 Aug 2014.
9.
Policy Statement on Health Canada’s working definition for nanomaterial—available online at: http://www.hc-sc.gc.ca/sr-sr/pubs/nano/pol-eng.php. Accessed 21 Aug 2014.
10.
Nanotechnology-based health products and food page—available online at: http://www.hc-sc.gc.ca/dhp-mps/nano-eng.php. Accessed 21 Aug 2014.
11.
Drug Submission Application Form for Human, Veterinary, Disinfectant Drugs and Clinical Trial Application/Attestation (HC/SC 3011)—available online at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/form/hc3011_sc3011-eng.php. Accessed 05 Nov 2014.
12.
Next-generation nanomedicines and nanosimilars: EU regulators’ initiatives relating to the development and evaluation of nanomedicines. Available online at: http://www.futuremedicine.com/doi/abs/10.2217/nnm.13.68. Accessed 21 Aug 2014 and published in Nanomedicine (2013) 8(5), 849–856, doi:10.2217/nnm.13.68.
13.
EMA website (nanotechnology page): http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000345.jsp&murl=menus/special_topics/special_topics.jsp&mid=WC0b01ac05800baed9. Accessed 21 Aug 2014.
14.
EMA draft reflection paper on the data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. Available online at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/03/WC500140351.pdf. Accessed 21 Aug 2014.
15.
The draft reflection paper on Data requirements for intravenous iron-based nano-colloidal products. Available online at: http://www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500149496&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3dc. Accessed 21 Aug 2014.
16.
The joint EMA/MHLW reflection paper on block copolymer micelle medicinal products. Available online at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/01/WC500159411.pdf. Accessed 21 Aug 2014.
17.
The EMA reflection paper on surface coating. Available online at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/08/WC500147874.pdf. Accessed 21 Aug 2014.
18.
Innovation Task Force (ITF) itfsecretariat@ema.europa.eu: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000334.jsp&mid=WC0b01ac05800ba1d9. Accessed 21 Aug 2014.
19.
EMA guidance for companies requesting scientific advice or protocol assistance. Available online at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000049.jsp&mid=WC0b01ac05800229b9. Accessed 21 Aug 2014.
20.
CHMP Scientific Advice and Novel methods qualification (e.g., biomarker): scientificadvice@ema.europa.eu http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000349.jsp&mid=WC0b01ac05800baedb. Accessed 21 Aug 2014.
21.
Qualification of novel methodologies for drug developments: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000319.jsp&mid=WC0b01ac0580022bb0. Accessed 21 Aug 2014.
22.
EMA SME Office: smeoffice@ema.europa.eu http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000059.jsp&mid=WC0b01ac05800240cc. Accessed 21 Aug 2014.
23.
Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm. 1995;25:91–7.CrossRefGoogle Scholar
24.
Petrelli F, Borgonova K, Barni S. Targeted delivery for breast cancer therapy: the history of nano-article-albumin-bound paclitaxel. Expert Opin Pharmacother. 2010;11:1413–32.CrossRefPubMedGoogle Scholar
25.
Zolnik BS, Sadrieh N. Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. Adv Drug Deliv Rev. 2009;61:422–7.CrossRefPubMedGoogle Scholar
26.
Sultana S, Khan MR, Kumar M, Kumar S, Ali M. Nanoparticles-mediated drug delivery approaches for cancer targeting: a review. J Drug Target. 2013;21:107–25.CrossRefPubMedGoogle Scholar
27.
Sayes CM. The relationships among structure, activity, and toxicity of engineered nanoparticles. KONA Powder Part J. 2014;31:10.CrossRefGoogle Scholar
28.
D’Addio SM, Prud’homme RK. Controlling drug nanoparticle formation by rapid precipitation. Adv Drug Deliv Rev. 2011;63(6):417–26. doi:10.1016/j.addr.2011.04.005.CrossRefPubMedGoogle Scholar
29.
Yu WW, Chang E, Falkner JC, Zhang J, Al-Somali AM, Sayes CM, et al. Forming biocompatible and nonaggregated nanocrystals in water using amphiphilic polymers. J Am Chem Soc. 2007;129(10):2871–9.CrossRefPubMedGoogle Scholar
30.
Sayes CM, Fortner JD, Guo W, Lyon D, Boyd D, Ausman K, et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 2004;4(10):1881–7.CrossRefGoogle Scholar
31.
Sayes CM, Reed KL, Warheit DB. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci. 2007;97(1):163–80.CrossRefPubMedGoogle Scholar
32.
Boyd BJ. Past and future evolution in colloidal drug delivery systems. Expert Opin Drug Deliv. 2008;5(1):69–85.CrossRefPubMedGoogle Scholar
33.
Leroux JC, Allemann E, Jaeghere FD, Doelker E, Gurny R. Biodegradable nanoparticles—from sustained release formulations to improved site specific drug delivery. J Control Release. 1996;39(2–3):339–50. doi:10.1016/0168-3659(95)00164-6.CrossRefGoogle Scholar
34.
Owens 3rd DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93–102.CrossRefPubMedGoogle Scholar
35.
Vonarbourg A, Passirani C, Saulnier P, Benoit JP. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials. 2006;27(24):4356–73.CrossRefPubMedGoogle Scholar
36.
Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505–15.CrossRefPubMedCentralPubMedGoogle Scholar
37.
Choi SW, Kim WS, Kim JH. Surface modification of functional nanoparticles for controlled drug delivery. J Dispers Sci Technol. 2003;24(3–4):475–87.CrossRefGoogle Scholar
38.
Dawson KA, Salvati A, Lynch I. Nanotoxicology: nanoparticles reconstruct lipids. Nat Nanotechnol. 2009;4:84–5.CrossRefPubMedGoogle Scholar
39.
Monopoli MP, Bombelli FB, Dawson KA. Nanobiotechnology: nanoparticle coronas take shape. Nat Nanotechnol. 2010;6(1):11–2. doi:10.1038/nnano.2011.267.CrossRefGoogle Scholar
40.
International Harmonization Conference guidelines: http://www.ich.org/products/guidelines.html. Accessed 21 Aug 2014.
41.
Kesisoglou F, Panmai S, Wu Y. Nanosizing—oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59:631–44.CrossRefPubMedGoogle Scholar
42.
Chen H, Khemtong C, Yang X, Chsang X, Gao J. Nanonozation strategies for poorly water-soluble drugs. Drug Discov Today. 2011;16:354–60.CrossRefPubMedGoogle Scholar
43.
Gao L, Liu G, Ma J, Wang X, Zhou L, Li X, et al. Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs. Pharm Res. 2012;30:307–24.CrossRefPubMedGoogle Scholar
44.
Narang A, Chang R, Hussain M. Pharmaceutical development and regulatory considerations for nanoparticles and nanoparticulate drug delivery systems. J Pharm Sci. 2013;102(11):3867–82. doi:10.1002/jps.23661.CrossRefPubMedGoogle Scholar
45.
Moschwitzer J. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm. 2013;453:142–56.CrossRefPubMedGoogle Scholar
46.
Kayaert P, Anne M, Van den Mooter G. Bead layering as a process to stabilize nanosuspensions: influence of drug hydrophobicity on nanocrystal reagglomeration following in vitro release from sugar sphere. J Pharm Pharmacol. 2011;63:1446–53.CrossRefPubMedGoogle Scholar
47.
Chaubal M, Popescu C. Conversions of nanosuspensions in to into dry powders by spray drying: a case study. Pharm Res. 2008;25:2302–8.CrossRefPubMedGoogle Scholar
48.
Dicko A, Frazier AA, Liboiron BD, Hindeliter A, et al. Intra- and inter-molecular interactions dictate the aggregation state of irinotecan co-encapsulated with floxuridine inside liposomes. Pharm Res. 2008;25:1702–13.CrossRefPubMedGoogle Scholar
49.
Gilday E, Nasrallah H. Clinical pharmacology of paliperidone palmitate—a parenteral long acting formulation for the treatment of schizophrenia. Rev Recent Clin Trials. 2011;7(1):2–9.CrossRefGoogle Scholar
50.
Shegokar R, Muller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1–2):129–39.CrossRefPubMedGoogle Scholar
51.
Muller R, Keck C. Challenges and solutions for the delivery of biotech drugs—a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol. 2004;113:151–70.CrossRefPubMedGoogle Scholar
52.
Merisko-Liversidge E, Liversidge G. Nanosizing oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev. 2011;63:427–40.CrossRefPubMedGoogle Scholar
53.
Peltonen L, Hirvonen J. Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods. J Pharm Pharmacol. 2010;62:1569–79.CrossRefPubMedGoogle Scholar
54.
Singare D, Marella S, Gowthamarjan K, Kulkarni G, Vooturi R, Rao P. Optimization of formulation and process variables of nanosuspensions: an industrial perspective. Int J Pharm. 2010;402:213–20.CrossRefPubMedGoogle Scholar
55.
Feldman EJ, Lancet JE, Kolitz JE, Ritchie EK, Roboz GJ, List AF, et al. First-in-man study of CPX-351: a liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia. J Clin Oncol. 2011;29:979–85. doi:10.1200/JCO.2010.30.5961.CrossRefPubMedGoogle Scholar
56.
Paciotti GF, Myer L, Weinreich D, Goia D, Pavel N, McLaughlin RE, et al. Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv. 2004;11:169–83.CrossRefPubMedGoogle Scholar
57.
Libutti SK, Paciotti GF, Byrnes AA, Alexander Jr HR, Gannon WE, Walker M, et al. Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin Cancer Res. 2010;16(24):6139–49.CrossRefPubMedCentralPubMedGoogle Scholar
58.
Kingston DGI, Tamarkin L, Paciotti GF. Conformationally constrained and nanoparticle-targeted paclitaxels. Pure Appl Chem. 2012;10:1361–74.Google Scholar
59.
Muller RH, Gohla S, Keck CM. State of the art of nanocrystals—special features, production, nanotoxicology aspects and intracellular deliver. Eur J Pharm Biopharm. 2011;78:1–9.CrossRefPubMedGoogle Scholar
60.
Zamboni WC, Torchilin V, Patri AK, Hrkach J, Stern S, Lee R, et al. Best practice s in cancer nanotechnology: perspective from NCI nanotechnology alliance. Clin Cancer Res. 2012;18(12):3229–41. doi:10.1158/1078-0432.CCR-11-2938.CrossRefPubMedCentralPubMedGoogle Scholar
61.
Duncan R, Gaspar R. Nanomedicine(s) under the microscope. Mol Pharm. 2011;8(6):2101–41.CrossRefPubMedGoogle Scholar
62.
Park JW, Benz CC, Martin FJ. Future directions of liposome- and immunoliposome-based cancer therapeutics. Semin Oncol. 2004;31(6 Suppl 13):196–205.CrossRefPubMedGoogle Scholar
63.
Zamboni WC, Yoshino K. Formulation and physiologic factors affecting the pharmacokinetics and pharmacodynamics of liposomal agents. Drug Deliv Syst. 2010;25(1):58–70.Google Scholar
64.
Caron WP, Song G, Kumar P, Rawal S, Zamboni WC. Pharmacokinetic and pharmacodynamic disposition of carrier-mediated agents. Clin Pharmacol Ther. 2012;91(5):802–12.CrossRefPubMedGoogle Scholar
65.
Moghimi SM, Parhamifar L, Ahmadvand D, Wibroe PP, Andresen TL, Farhangrazi ZS, et al. Particulate systems for targeting of macrophages: basic and therapeutic concepts. J Innate Immunol. 2012;4(5–6):509–28.CrossRefGoogle Scholar
66.
Kumar P, Caron WP, Song G, Rawal S, Zamboni WC. Nanoparticle effects on the interaction with cells of the mononuclear phagocytic system. In: Dobrovolskaia M, editor. Immunological properties of engineered nanomaterials. First edition. World Scientific, in press. 2013.Google Scholar
67.
Caron WP, Lay JC, Fong AM, La-Beck NM, Kumar P, Newman SE, et al. Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology. J Pharmacol Exp Ther. 2013;347(3):599–606. doi:10.1124/jpet.113.208801.CrossRefPubMedCentralPubMedGoogle Scholar
68.
Schell RF, Sidone BJ, Caron WP, Walsh MD, White TF, Zamboni BA, et al. Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Nanomedicine. 2014;10:109–17.CrossRefPubMedGoogle Scholar
69.
Zamboni WC, Strychor S, Maruca L, Ramalingam S, Zamboni BA, Wu H, et al. Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. Clin Pharmacol Ther. 2009;86(5):519–26. doi:10.1038/clpt.2009.141.CrossRefPubMedGoogle Scholar
70.
Gabizon A, Isacson R, Rosengarten O, Tzemach D, Shmeeda H, Sapir R. An open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin. Cancer Chemother Pharmacol. 2008;61(4):695–702.CrossRefPubMedGoogle Scholar
71.
La-Beck NM, Zamboni BA, Gabizon A, Schmeeda H, Amantea M, Gehrig PA, et al. Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol. 2012;69(1):43–50.CrossRefPubMedGoogle Scholar
72.
Wu H, Ramanathan RK, Zamboni BA, Strychor S, Ramalingam S, Edwards RP, et al. Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients. Int J Nanomedicine. 2012;7:5555–64. doi:10.2147/IJN.S35751.CrossRefPubMedCentralPubMedGoogle Scholar
73.
Zamboni WC, Maruca LJ, Strychor S, Zamboni BA, Ramalingam S, Edwards RP, et al. Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors. J Liposome Res. 2011;21(2):158–65. doi:10.3109/08982104.2010.496085.CrossRefPubMedGoogle Scholar
74.
Charrois GJ, Allen TM. Multiple injections of pegylated liposomal doxorubicin: pharmacokinetics and therapeutic activity. J Pharmacol Exp Ther. 2003;306(3):1058–67.CrossRefPubMedGoogle Scholar
75.
Suzuki T, Ichihara M, Hyodo K, Yamamoto E, Ishida T, Kiwada H, et al. Accelerated blood clearance of PEGylated liposomes containing doxorubicin upon repeated administration to dogs. Int J Pharm. 2012;436(1–2):636–43. doi:10.1016/j.ijpharm.2012.07.049.CrossRefPubMedGoogle Scholar
76.
Crist RM et al. Common pitfalls in nanotechnology: lessons learned from NCI’s Nanotechnology Characterization Laboratory. Integr Biol (Camb). 2013;5:66–73.CrossRefGoogle Scholar
77.
Skoczen SL, Potter TM, Dobrovolskaia MA. In vitro analysis of nanoparticle uptake by macrophages using chemiluminescence. Methods Mol Biol. 2011;697:255–61.CrossRefPubMedGoogle Scholar
78.
Song G, Moore S, Tarrant T, Dobrovolskaia M, et al. 126: Relationship between complement factors and CC chemokines and the pharmacokinetics (PK) and pharmacodynamics (PD) of PEGylated liposomal doxorubicin (PLD) in patients with refractory epithelial ovarian cancer (EOC). Eur J Cancer. 2012;48 SUPPL 6:39–40.CrossRefGoogle Scholar
79.
Kumar P, Caron WP, Song G, Gallagher K, et al. Relationship between serum hormone levels and pharmacokinetics (PK) of PEGylated liposomal doxorubicin (PLD) in patients with refractory ovarian cancer. Cancer Res. 2012;72(8 SUPPL 1). doi: 10.1158/1538-7445.AM2012-2673
80.
Caron WP, Song G, Kumar P, Rawal S, Zamboni WC. Interpatient pharmacokinetic and pharmacodynamic variability of carrier-mediated anticancer agents. Clin Pharmacol Ther. 2012;91:802–12.CrossRefPubMedGoogle Scholar
81.
Maeda H, Nakamura N, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65:71–9.CrossRefPubMedGoogle Scholar
82.
Gregoriadis G. Drug entrapment in liposomes. FEBS Lett. 1973;36:292–6.CrossRefPubMedGoogle Scholar
83.
Birrenbach G, Speiser PP. Polymerized micelles and their use as adjuvants in immunology. J Pharm Sci. 1976;65:1763–6.CrossRefPubMedGoogle Scholar
84.
Juliano RL, Stamp D. Pharmacokinetics of liposome-encapsulated anti-tumor drugs: studies with vinblastine, actinomycin D, cytosine, arabinoside, and daunomycin. Biochem Pharmacol. 1978;27:21–7.CrossRefPubMedGoogle Scholar
85.
FDA guidance for industry: nonclinical studies for the safety evaluation of pharmaceutical excipients: May 2005: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm079250.pdf. Accessed 21 Aug 2014.
86.
FDA Draft Guidance for Industry: liposome drug products: CMC, human pharmacokinetic and bioavailability; and labeling documentation: August 2002: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070570.pdf. Accessed 21 Aug 2014.
87.
FDA draft guidance on doxorubicin hydrochloride: November 2013. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm199635.pdf. Accessed 21 Aug 2014.
88.
FDA draft guidance on iron sucrose: November 2013: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM297630.pdf. Accessed 21 Aug 2014.
89.
FDA draft guidance on aprepitant: November 2008 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm082548.pdf. Accessed 21 Aug 2014.
90.
Health Canada website http://hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/index-eng.php. Accessed 21 Aug 2014.
91.
Draft Guidance for Industry and FDA Staff: Classification of products as drugs and devices & additional product classification issues, June 2011. Available from Office of Combination Products: http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/officeofscienceandhealthcoordination/ucm2018184.htm Accessed 21 Aug 2014. At: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM258957.pdf. Accessed 21 Aug 2014.
92.
Guidance document: factors influencing the classification of products at the device-drug interface available online at: http://www.hc-sc.gc.ca/dhp-mps/dev-drug-instr-drogue/class_prod_gd_ld-eng.php. Accessed 21 Aug 2014.
93.
Drug/medical device combination products: http://hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/pol/combo_mixte_pol_2006-eng.php. Accessed 21 Aug 2014.
94.
Health Canada draft guidance document—drug master files (DMFs) is available at: http://hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/chem/draft_ebauche_dmf_fmm_guide_ld-eng.php. Accessed 21 Aug 2014.
95.
FDA guidance for industry: formal meetings between the FDA and sponsors or applicants: May 2009: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm153222.pdf. Accessed 21 Aug 2014.
96.
Health Canada guidance for industry: food and drugs act and regulations: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/mgmt-gest/mands_gespd-eng.php. Accessed 21 Aug 2014.
97.
Commission Recommendation 2011/696/EU, OJ L 275, 20.10.2011. Available online at: http://ec.europa.eu/environment/chemicals/nanotech/pdf/commission_recommendation.pdf.
98.
Van Buskirk GA, Asotra S, Balducci C, Basu P, DiDonato G, Dorantes A, et al. Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm. AAPS Pharm Sci Technol. 2014;15:665–93. doi:10.1208/s12249-014-0087-x.CrossRefGoogle Scholar

Copyright information

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.PfizerGroton LaboratoriesGrotonUSA
2.Janssen Pharmaceutica, Johnson and JohnsonBeerseBelgium
3.Center for Drug Evaluation and ResearchUnited States Food and Drug AdministrationSilver SpringUSA
4.Celator Pharmaceuticals, Inc.EwingUSA
5.United States Food and Drug AdministrationSilver SpringUSA
6.BASF CorporationEcology and SafetyFlorham ParkUSA
7.Merck and Co.West PointUSA
8.European Medicines AgencyLondonUK
9.Nanomedicines AllianceWashingtonUSA
10.Vertex Pharmaceuticals IncorporatedBostonUSA
11.Office of the CommissionerUnited States Food and Drug AdministrationSilver SpringUSA
12.Chemical and Biological Engineering, School of Engineering and Applied SciencePrinceton UniversityPrincetonUSA
13.Center for Food Safety and Applied NutritionUnited States Food and Drug AdministrationSilver SpringUSA
14.RTI InternationalResearch Triangle ParkUSA
15.Health Canada, Health Protection BranchOttawaCanada
16.Biologics Consulting GroupAlexandriaUSA
17.CytImmuneRockvilleUSA
18.UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology ExcellenceUniversity of North CarolinaChapel HillUSA
19.Wildcat Pharmaceutical Development CenterHoustonUSA

About this article

CrossMark

Cite this article as:: Bartlett, J.A., Brewster, M., Brown, P. et al. AAPS J (2015) 17: 44. doi:10.1208/s12248-014-9701-9

DOI 10.1208/s12248-014-9701-9
Publisher Name Springer US
Online ISSN 1550-7416

Published in cooperation with
The American Association of Pharmaceutical Scientists

Personalised recommendations

Actions

Unlimited access to the full article
Instant download
Include local sales tax if applicable

Subscribe to Journal

Get Access to

The AAPS Journal

for the whole of 2017

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

Abstract

KEY WORDS

Abbreviations

Copyright information

Authors and Affiliations

Personalised recommendations

Cookies