Regulatory Considerations for Cancer Drug Products Containing Nanomaterials

  • Mamta Kapoor
  • Kathryn Hughes
  • Katherine M. TynerEmail author
Part of the Bioanalysis book series (BIOANALYSIS, volume 5)


Applications for new pharmaceuticals in the USA are reviewed by the FDA’s Center for Drug Evaluation and Research (FDA/CDER), which evaluates the safety and efficacy of both drug substances and drug products. The degree of innovation and variety in the drug products containing nanomaterials is broad, and the FDA has conceptual and analytical frameworks to capture consistently the risks introduced by new therapeutic approaches. When reviewing drug product applications the Agency considers the entire product, from the data demonstrating clinical efficacy to the chemistry, production, storage, and delivery method(s). These last four areas are collectively evaluated as the quality attributes of a drug, and FDA determined that these have particular importance for drug products containing nanomaterials. The relevant quality attributes are discussed in detail in this chapter following a brief overview of nanomaterials within products designed to treat cancer and a description of the regulatory structure in which applications for cancer therapeutics are reviewed.


Nanomaterials United States Food and Drug Administration Center for Drug Evaluation and Research Drug product quality Drug products Active pharmaceutical ingredient Liposome Nanocrystals Critical quality attributes IND NDA ANDA Nanotechnology in cancer therapeutics Doxil® DaunoXome® Generic drugs 505b(1) 505b(2) 505(j) BLA Fast track designation Breakthrough therapy designation Accelerated approval Priority review designation Drug products containing nanomaterials Drug substance 


  1. 1.
    NANOTECHNOLOGY MARKET- Nanotechnology Markets in Healthcare & Medicine (2014) Drug Development & Delivery. Accessed 20 Jun 2016
  2. 2.
    Chidambaram, M., Manavalan, R., Kathiresan, K.: Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J. Pharm. Pharm. Sci. 14(1), 67–77 (2011)CrossRefGoogle Scholar
  3. 3.
    Suzuki, R., Omata, D., Oda, Y., Unga, J., Negishi, Y., Maruyama, K.: Cancer therapy with nanotechnology-based drug delivery systems: applications and challenges of liposome technologies for advanced cancer therapy. Nanomater. Pharmacol. 457–482 (2016)Google Scholar
  4. 4.
    Thakor, A.S., Gambhir, S.S.: Nanooncology: the future of cancer diagnosis and therapy. CA Cancer J. Clin. 63(6), 395–418 (2013)CrossRefGoogle Scholar
  5. 5.
    Blanco, E., Hsiao, A., Mann, A.P., Landry, M.G., Meric-Bernstam, F., Ferrari, M.: Nanomedicine in cancer therapy: innovative trends and prospects. Cancer Sci. 102(7), 1247–1252 (2011). Scholar
  6. 6.
    Sumer, B., Gao, J.: Theranostic nanomedicine for cancer. Nanomedicine (Lond.). 3(2), 137–140 (2008). Scholar
  7. 7.
    D’Mello, S.R., Cruz, C.N., Chen, M.-L., Kapoor, M., Lee, S.L., Tyner, K.M.: The evolving landscape of drug products containing nanomaterials in the United States. Nat. Nano. 12, 523–529 (2017)CrossRefGoogle Scholar
  8. 8.
    Statistics for Different Kinds of Cancer. Centers for Disease Control and Prevention. Accessed 03 Jun 2016
  9. 9.
    National Cancer Institure. Cancer Moonshot. Accessed 10 Jul 2016
  10. 10.
    Gewirtz, D.A., Bristol, M.L., Yalowich, J.C.: Toxicity issues in cancer drug development. Curr. Opin. Investig Drugs. 11(6), 612–614 (2010)Google Scholar
  11. 11.
    Liversidge, G.G., Cundy, K.C.: Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int. J. Pharm. 125(1), 91–97 (1995). Scholar
  12. 12.
    Jinno, J.-i., Kamada, N., Miyake, M., Yamada, K., Mukai, T., Odomi, M., Toguchi, H., Liversidge, G.G., Higaki, K., Kimura, T.: Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. J. Control Release. 111(1–2), 56–64 (2006). Scholar
  13. 13.
    Pillai, G.: Nanomedicines for cancer therapy: an update of FDA approved and those under various stages of development. SOJ Pharm. Pharm. Sci. 1(2), 13 (2014)Google Scholar
  14. 14.
    Peer, D., Karp, J.M., Hong, S., Farokhzad, O.C., Margalit, R., Langer, R.: Nanocarriers as an emerging platform for cancer therapy. Nat. Nano. 2(12), 751–760 (2007)CrossRefGoogle Scholar
  15. 15.
    Brown, J.M., Giaccia, A.J.: The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 58(7), 1408–1416 (1998)Google Scholar
  16. 16.
    Hobbs, S.K., Monsky, W.L., Yuan, F., Roberts, W.G., Griffith, L., Torchilin, V.P., Jain, R.K.: Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc. Natl. Acad. Sci. U. S. A. 95(8), 4607–4612 (1998)CrossRefGoogle Scholar
  17. 17.
    Maeda, H.: The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv. Enzym. Regul. 41(1), 189–207 (2001). Scholar
  18. 18.
    Maeda, H., Nakamura, H., 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. 65(1), 71–79 (2013). Scholar
  19. 19.
    Weissig, V., Pettinger, T.K., Murdock, N.: Nanopharmaceuticals (part 1): products on the market. Int. J. Nanomedicine. 9, 4357–4373 (2014). Scholar
  20. 20.
    Yuan, Y., Zhang, L., Cao, H., Yang, Y., Zheng, Y., X-j, Y.: A polyethylenimine-containing and transferrin-conjugated lipid nanoparticle system for antisense oligonucleotide delivery to AML. Biomed. Res. Int. 2016, 8 (2016). Scholar
  21. 21.
    Hamaguchi, T., Matsumura, Y., Nakanishi, Y., Muro, K., Yamada, Y., Shimada, Y., Shirao, K., Niki, H., Hosokawa, S., Tagawa, T., Kakizoe, T.: Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts. Cancer Sci. 95(7), 608–613 (2004). Scholar
  22. 22.
    Clinical Trials Worldwide. Accessed 12 Aug 2016
  23. 23.
    Davis, M.E., Chen, Z., Shin, D.M.: Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771–782 (2008)CrossRefGoogle Scholar
  24. 24.
    Thanki, K., Kushwah, V., Jain, S.: Recent advances in tumor targeting approaches. In: Targeted Drug Delivery: Concepts and Design, pp. 41–112. Springer, Cham (2015)Google Scholar
  25. 25.
    Byrne, J.D., Betancourt, T., Brannon-Peppas, L.: Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv. Drug Deliv. Rev. 60(15), 1615–1626 (2008). Scholar
  26. 26.
    Rahman, A.M., Yusuf, S.W., Ewer, M.S.: Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int. J. Nanomedicine. 2(4), 567–583 (2007)Google Scholar
  27. 27.
    Morton, J.G., Day, E.S., Halas, N.J., West, J.L.: Nanoshells for photothermal cancer therapy. In: Grobmyer, S.R., Moudgil, B.M. (eds.) Cancer Nanotech: Methods and Protocols, pp. 101–117. Humana Press, Totowa, NJ (2010). Scholar
  28. 28.
    Stern, J.M., Stanfield, J., Kabbani, W., Hsieh, J.-T., Cadeddu, J.A.: Selective prostate cancer thermal ablation with laser activated gold nanoshells. J. Urol. 179(2), 748–753 (2008). Scholar
  29. 29.
    First patient treated with MagForce's NanoTherm therapy for recurrent glioblastoma (2011) News Medical. Accessed 23 Jun 2016
  30. 30.
    Hamburg, M.A.: Science and regulation. FDA's approach to regulation of products of nanotechnology. Science. 336(6079), 299–300 (2012). Scholar
  31. 31.
    Guidance for Industry: Considering whether an FDA-regulated product involves the application of nanotechnology (2014) U.S. Food and Drug Administration.
  32. 32.
    Guidances (Drugs). U.S. Food and Drug Administration. Accessed 04 May 2016
  33. 33.
    Draft Guidance on Lanreotide Acetate (2014). U.S. Food and Drug Administration Accessed 03 Jul 2016
  34. 34.
    D'Souza, S.S., DeLuca, P.P.: Methods to assess in vitro drug release from injectable polymeric particulate systems. Pharm. Res. 23(3), 460–474 (2006). Scholar
  35. 35.
    FDA Center for Drug Evaluation and Research (CDER) Strategic Plan 2013–2017. U.S. Food and Drug Administration. Accessed 10 May 2016
  36. 36.
    Drugs@FDA Glossary of Terms, U.S. Food and Drug Administration. Accessed 20 Jun 2016
  37. 37.
    Investigational New Drug (IND) Application, U.S. Food and Drug Administration. Accessed 05 July 2016
  38. 38.
    Maeda, H.: Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J. Control. Release. 164(2), 138–144 (2012). Scholar
  39. 39.
    Ozcan, G., Ozpolat, B., Coleman, R.L., Sood, A.K., Lopez-Berestein, G.: Preclinical and clinical development of siRNA-based therapeutics. Adv. Drug Deliv. Rev. 87, 108–119 (2015). Scholar
  40. 40.
    The Drug Development Process, Step 3: Clinical Research, U.S. Food and Drug Administration. Accessed 08 Aug 2016
  41. 41.
    NDA 505(b)(1) of the FD&C Act, U.S. Food and Drug Administration. Accessed 17 Aug 2016
  42. 42.
    What is 505(b)(2)? Camargo Pharmaceutical Services (2016): The Global 505(b)(2) Experts. Accessed 07 July 2016
  43. 43.
    Draft Guidance for Industry: Applications Covered by Section 505(b)(2) (1999) U.S. Food and Drug Administration.
  44. 44.
    NDA 20–2062/S-064 approval package for Taxol Injection, Center for Drug Evaluation and Research, U.S. Food and Drug Administration. Accesssed 23 July 2016
  45. 45.
    Abraxane paclitaxel protein-bound particles for injectable suspension, Oncologic Drugs Advisory Committee Meeting, Sept 7, 2006, Abraxis Bioscience. Accessed 14 Sept 2016
  46. 46.
  47. 47.
    Drugs@FDA Glossary of Terms, U.S. Food and Drug Administration. Accessed 17 May 2016
  48. 48.
    Transfer of therapeutic biological products to the Center for Drug Evaluation and Research (2003) U.S. Food and Drug Administration. Accessed 30 Jul 2016
  49. 49.
    Guidance for Industry ANDA Submissions — Content and Format of Abbreviated New Drug Applications (2014) U.S. Food and Drug Administration.
  50. 50.
    Abbreviated New Drug Application (ANDA): Generics, U.S. Food and Drug Administration. Accessed 09 Sept 2016
  51. 51.
    Draft Guidance on best practices for communication between IND sponsors and FDA during drug development guidance for industry and review staff (2015) U.S. Food and Drug Administration.
  52. 52.
    Cruz, C.N., Tyner, K.M., Velazquez, L., Hyams, K.C., Jacobs, A., Shaw, A.B., Jiang, W., Lionberger, R., Hinderling, P., Kong, Y., Brown, P.C., Ghosh, T., Strasinger, C., Suarez-Sharp, S., Henry, D., Van Uitert, M., Sadrieh, N., Morefield, E.: CDER risk assessment exercise to evaluate potential risks from the use of nanomaterials in drug products. AAPS J. 15(3), 623–628 (2013). Scholar
  53. 53.
    Gudiance for Industry: Liposome Drug Products. Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation. (2018) U.S. Food and Drug Administration.
  54. 54.
    Pharmaceutical Development Q8(R2) (2009). International Conference on Harmonisation. Accessed 04 Jun 2016
  55. 55.
    Guidance for Industry: Changes to an approved NDA or ANDA (2004) U.S. Food and Drug Administration.
  56. 56.
    Tyner, K.M., Zou, P., Yang, X., Zhang, H., Cruz, C.N., Lee, S.L.: Product quality for nanomaterials: current U.s. experience and perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7(5), 640–654 (2015). Scholar
  57. 57.
    Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics (2014) U.S. Food and Drug Administration.
  58. 58.
    Cerulean Receives FDA Fast Track Designation for CRLX101 for the Treatment of Platinum-Resistant Ovarian Cancer (2016) Business Wire- A Berkshire Hathaway company. Accessed 12 Aug 2016
  59. 59.
    Lancet, J.E., Uy, G.L., Cortes, J.E., Newell, L.F., Lin, T.L., Ritchie, E.K., Stuart, R.K., Strickland, S.A., Hogge, D., Solomon, S.R., Stone, R.M., Bixby, D.L., Kolitz, J.E., Schiller, G.J., Wieduwilt, M.J., Ryan, D.H., Hoering, A., Chiarella, M., Louie, A.C., Medeiros, B.C., Lee, H.: Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J. Clin. Oncol. 34. (suppl; abstr 7000, 7000 (2016)CrossRefGoogle Scholar
  60. 60.
    Johnson, J.R., Ning, Y.-M., Farrell, A., Justice, R., Keegan, P., Pazdur, R.: Accelerated approval of oncology products: the Food and Drug Administration experience. J. Natl. Cancer Inst. 103(8), 636–644 (2011). Scholar
  61. 61.
    FDA approves Onivyde for advanced pancreatic cancer (2015) American Cancer Society, Inc. Accessed 14 Jan 2016
  62. 62.
    Zheng, N., Sun, D.D., Zou, P., Jiang, W.: Scientific and regulatory considerations for generic complex drug products containing Nanomaterials. AAPS J. 19, 619 (2017). Scholar
  63. 63.
    Search for FDA Guidance Documents, U.S. Food and Drug Administration. Accessed 10 Oct 2016
  64. 64.
    New Drug Development and Review Process, U.S. Food and Drug Administration. Accessed 13 Aug 2016
  65. 65.
    CTI BioPharma announces independent DMC recommendation to continue GOG-0212 Phase 3 study of OPAXIO™ as maintenance therapy in ovarian cancer, an NRG Oncology/GOG Study (2015) CTI BioPharma Corp. Accessed 02 Aug 2016
  66. 66.
    BIND Therapeutics presents positive Phase 2 results highlighting potential of BIND-014 as novel anti-cancer treatment at Q3W dosing schedule for patients with non-small cell lung cancer at 26th EORTC-NCI-AACR Annual Symposium (2014) Business Wire- A Berkshire Hathaway company. Accessed 01 Aug 2016 (2014)
  67. 67.
    Awada, A., Bondarenko, I.N., Bonneterre, J., Nowara, E., Ferrero, J.M., Bakshi, A.V., Wilke, C., Piccart, M.: A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC). Ann. Oncol. 25(4), 824–831 (2014). Scholar
  68. 68.
    Batist, G., Gelmon, K.A., Chi, K.N., Miller, W.H., Chia, S.K.L., Mayer, L.D., Swenson, C.E., Janoff, A.S., Louie, A.C.: Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin. Cancer Res. 15(2), 692–700 (2009). Scholar
  69. 69.
    Boorjian, S.A., Milowsky, M.I., Kaplan, J., Albert, M., Cobham, M.V., Coll, D.M., Mongan, N.P., Shelton, G., Petrylak, D., Gudas, L.J., Nanus, D.M.: Phase 1/2 clinical trial of interferon α2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma. J. Immunother. 30(6), 655–662 (2007). Scholar
  70. 70.
    Butts, C.A., Socinski, M.A., Mitchell, P., Thatcher, N., Havel, L., Krzakowski, M.J., Nawrocki, S., Ciuleanu, T.-E., Bosquee, L., Perez, J.M.T., Spira, A.I., Tremblay, L., Nyman, J., Ramlau, R., Helwig, C., Falk, M.H., Shepherd, F.A.: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer. J. Clin. Oncol. 31, (2013). suppl; abstr 7500Google Scholar
  71. 71.
    Calvo, E., Hoch, U., Maslyar, D.J., Tolcher, A.W.: Dose-escalation phase I study of NKTR-105, a novel pegylated form of docetaxel. J. Clin. Oncol. 28(15 Suppl), (2010). abstr TPS160CrossRefGoogle Scholar
  72. 72.
    Gad, S.C., Sharp, K.L., Montgomery, C., Payne, J.D., Goodrich, G.P.: Evaluation of the toxicity of intravenous delivery of auroshell particles (gold–silica nanoshells). Int. J. Toxicol. 31(6), 584–594 (2012)CrossRefGoogle Scholar
  73. 73.
    Gonzalez-Angulo, A.M., Meric-Bernstam, F., Chawla, S., Falchook, G., Hong, D., Akcakanat, A., Chen, H., Naing, A., Fu, S., Wheler, J., Moulder, S., Helgason, T., Li, S., Elias, I., Desai, N., Kurzrock, R.: Weekly nab-rapamycin in patients with advanced nonhematologic malignancies: final results of a phase 1 trial. Clin. Cancer Res. 19(19), 5474–5484 (2013). Scholar
  74. 74.
    Hong, D.S., Kang, Y.-K., Brenner, A.J., Sachdev, J.C., Ejadi, S., Borad, M.J., Kim, T.-Y., Lim, H.Y., Park, K., Becerra, C., Bader, A.G., Stoudemire, J., Smith, S., Kim, S., Beg, M.S.: MRX34, a liposomal miR-34 mimic, in patients with advanced solid tumors: final dose-escalation results from a first-in-human phase I trial of microRNA therapy. J. Clin. Oncol. 34 .(suppl; abstr 2508, 2508 (2016)CrossRefGoogle Scholar
  75. 75.
    Kim, D.-W., Kim, S.-Y., Kim, H.-K., Kim, S.-W., Shin, S., Kim, J., Park, K., Lee, M., Heo, D.: Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer. Ann. Oncol. 18(12), 2009–2014 (2007)CrossRefGoogle Scholar
  76. 76.
    Landen, C.N., Chavez-Reyes, A., Bucana, C., Schmandt, R., Deavers, M.T., Lopez-Berestein, G., Sood, A.K.: Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 65(15), 6910 (2005)CrossRefGoogle Scholar
  77. 77.
    Libutti, S.K., Paciotti, G.F., Byrnes, A.A., Alexander, H.R., Gannon, W.E., Walker, M., Seidel, G.D., Yuldasheva, N., Tamarkin, L.: Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin. Cancer Res. 16(24), 6139–6149 (2010). Scholar
  78. 78.
    Nagykalnai, T.: Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin. Magy. Onkol. 54(4), 359–367 (2010)CrossRefGoogle Scholar
  79. 79.
    Oerlemans, C., Bult, W., Bos, M., Storm, G., Nijsen, J.F.W., Hennink, W.E.: Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm. Res. 27(12), 2569–2589 (2010). Scholar
  80. 80.
    Perez, E.A., Awada, A., O'Shaughnessy, J., Rugo, H.S., Twelves, C., Im, S.-A., Gómez-Pardo, P., Schwartzberg, L.S., Diéras, V., Yardley, D.A., Potter, D.A., Mailliez, A., Moreno-Aspitia, A., Ahn, J.-S., Zhao, C., Hoch, U., Tagliaferri, M., Hannah, A.L., Cortes, J.: Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 16(15), 1556–1568 (2015). Scholar
  81. 81.
    Phan, A., Takimoto, C., Adinin, R., Wood, L., Xiong, H., Matsuno, K., Konno, S., Fujisawa, T., Beeram, M.: Open label phase I study of MBP-426, a novel formulation of oxaliplatin, in patients with advanced or metastatic solid tumors. Mol. Cancer Ther. 6(11 Supplement), C115–C115 (2007)Google Scholar
  82. 82.
    Schultheis, B., Strumberg, D., Santel, A., Vank, C., Gebhardt, F., Keil, O., Lange, C., Giese, K., Kaufmann, J., Khan, M.: First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J. Clin. Oncol. 32(36), 4141–4148 (2014)CrossRefGoogle Scholar
  83. 83.
    Storka, A., Vcelar, B., Klickovic, U., Gouya, G., Weisshaar, S., Aschauer, S., Bolger, G., Helson, L., Wolzt, M.: Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans. Int. J. Clin. Pharmacol. Ther. 53(1), 54–65 (2015). Scholar
  84. 84.
    Tabernero, J., Shapiro, G.I., LoRusso, P.M., Cervantes, A., Schwartz, G.K., Weiss, G.J., Paz-Ares, L., Cho, D.C., Infante, J.R., Alsina, M., Gounder, M.M., Falzone, R., Harrop, J., White, A.C.S., Toudjarska, I., Bumcrot, D., Meyers, R.E., Hinkle, G., Svrzikapa, N., Hutabarat, R.M., Clausen, V.A., Cehelsky, J., Nochur, S.V., Gamba-Vitalo, C., Vaishnaw, A.K., Sah, D.W.Y., Gollob, J.A., Burris, H.A.: First-in-Humans Trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 3(4), 406–417 (2013). Scholar
  85. 85.
    Wetzler, M., Thomas, D.A., Wang, E.S., Shepard, R., Ford, L.A., Heffner, T.L., Parekh, S., Andreeff, M., O'Brien, S., Kantarjian, H.M.: Phase I/II trial of nanomolecular liposomal annamycin in adult patients with relapsed/refractory acute lymphoblastic leukemia. Clin. Lymphoma Myeloma Leuk. 13(4), 430–434 (2013). Scholar
  86. 86.
    Yarmolenko, P.S., Zhao, Y., Landon, C., Spasojevic, I., Yuan, F., Needham, D., Viglianti, B.L., Dewhirst, M.W.: Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours. Int. J. Hyperth. 26(5), 485–498 (2010). Scholar
  87. 87.
    Young, C., Schluep, T., Hwang, J., Eliasof, S.: CRLX101 (formerly IT-101)–a novel nanopharmaceutical of camptothecin in clinical development. Curr. Bioact. Compd. 7(1), 8–14 (2011). Scholar
  88. 88.
    Zhang, J.A., Anyarambhatla, G., Ma, L., Ugwu, S., Xuan, T., Sardone, T., Ahmad, I.: Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation. Eur. J. Pharm. Biopharm. 59(1), 177–187 (2005). Scholar
  89. 89.
    Ahmad, A., Sheikh, S., Taran, R., Srivastav, S.P., Prasad, K., Rajappa, S.J., Kumar, V., Gopichand, M., Paithankar, M., Sharma, M., Rane, R.C., Ahmad, I.: Therapeutic efficacy of a novel nanosomal docetaxel lipid suspension compared with taxotere in locally advanced or metastatic breast cancer patients. Clin. Breast Cancer. 14(3), 177–181 (2014). Scholar
  90. 90.
    Senzer, N., Nemunaitis, J., Nemunaitis, D., Bedell, C., Edelman, G., Barve, M., Nunan, R., Pirollo, K.F., Rait, A., Chang, E.H.: Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol. Ther. 21(5), 1096–1103 (2013). Scholar
  91. 91.
    Stathopoulos, G.P., Boulikas, T.: Lipoplatin formulation review article. J. Drug. Deliv. 2012, 1 (2012). Scholar
  92. 92.
    Sapsford, K.E., Lauritsen, K., Tyner, K.M.: Current perspectives on the US Food and Drug Administration’s regulatory framework for intelligent drug delivery systems. Ther. Deliv. 3(12), 1383–1394 (2012). Scholar

Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  • Mamta Kapoor
    • 1
  • Kathryn Hughes
    • 1
  • Katherine M. Tyner
    • 1
    Email author
  1. 1.Center for Drug Evaluation and Research, US Food and Drug AdministrationSilver SpringUSA

Personalised recommendations