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Liposomal Drug Product Development and Quality: Current US Experience and Perspective

  • Review Article
  • Theme: Nanotechnology in Complex Drug Products: Learning from the Past, Preparing for the Future
  • Published:
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ABSTRACT

Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug’s pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

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Notes

  1. Note: According to 21CFR 320.31, for submissions involving NCEs or cytotoxic drugs, companies are required to submit a BioIND (bioequivalence studies at dose > maximum label) prior to the ANDA submission. Further, as per MAPP 5210.5, Bio-INDs must have complete information on chemistry, manufacturing, and controls, and not only the bioequivalence study protocol, so that the review chemist can adequately evaluate the safety of the drug product.

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Authors and Affiliations

  1. Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Mamta Kapoor, Sau L. Lee & Katherine M. Tyner

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  1. Mamta Kapoor
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Correspondence to Katherine M. Tyner.

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The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

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Guest Editors: Katherine Tyner, Sau (Larry) Lee, and Marc Wolfgang

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Kapoor, M., Lee, S.L. & Tyner, K.M. Liposomal Drug Product Development and Quality: Current US Experience and Perspective. AAPS J 19, 632–641 (2017). https://doi.org/10.1208/s12248-017-0049-9

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