Abstract
Liposomes are vesicular (phospho)lipid-based drug carrier systems in the nanometer/micrometer range. The therapeutic performance of these ‘composite’ drug products heavily depends on their supramolecular structure. They are heterodisperse, difficult to fully characterize by physicochemical means and produced via complex manufacturing processes. This renders them part of the NBCD group.
The first liposome based drug formulation received market authorization over 20 years ago (Ambisome™ 1990). Since then a number of liposome drug products were approved by the FDA and the EM(E)A. The first generic versions of the innovator products are now being registered.
In this chapter the CMC (Chemistry, Manufacturing and Control) aspects of liposomes will be discussed, followed by a short overview of pharmacological aspects (e.g., pharmacokinetics/disposition, dosing, hypersensitivity). The regulatory landscape as it developed over the years is described next, followed by reflections on the future of this family of lipid, vesicular drug carrier systems.
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Abbreviations
- AA:
-
Anaplastic astrocytoma (grade III)
- ABC:
-
Accelerated blood clearance
- ADME:
-
Absorption, distribution, metabolism and excretion
- ANDA:
-
Abbreviated New Drug Application
- API:
-
Active Pharmaceutical Ingredient
- AUC:
-
Area under the Curve
- CARPA:
-
Complement Activation-Related Pseudo-Allergy
- CBG-MEB:
-
College ter Beoordeling van Geneesmiddelen—Medicines Evaluation Board
- CHMP:
-
Committee for Medicinal Products for Human Use
- Chol:
-
Cholesterol
- CMC:
-
Chemistry, Manufacturing and Control
- CTD:
-
Common Technical Document
- DLS:
-
Dynamic Light Scattering
- DMPC:
-
Dimyristoylphosphatidylcholine
- DOPC:
-
Dioleylphosphatidylcholine
- DOPS:
-
Dioleylphospatidylserine
- DPPC:
-
Dipalmitoylphosphatidylcholine
- DPPG:
-
Dipalmitoylphosphatidylglycerol
- DSC:
-
Differential Scanning Calorimetry
- DSPC:
-
Distearoylphosphatidylcholine
- DSPE-PEG:
-
Distearoylphosphatidylethanolamine polyethyleneglycol
- DSPG:
-
Distearoylphosphatidylglycerol
- ELSD:
-
Evaporative Light scattering detection
- EPAR:
-
European Public Assessment Report
- EPC:
-
Egg Phosphatidylcholine
- EPR:
-
Enhanced Permeability and Retention
- FACS:
-
Fluorescence Activated Cytometric Cell Sorting
- FDA:
-
Food and Drug Administration
- FFF:
-
FieldFlow Fractionation
- GBM:
-
Glioblastoma Multiforme (grade IV)
- HSPC:
-
Hydrogenated Soy Bean Phosphatidylcholine
- ICH:
-
International Conference on Harmonization
- IVR:
-
In Vitro Release
- MPS:
-
Mononuclear Phagocyte System
- MS:
-
Mass Spectrometry
- NA:
-
Not Assessable
- NBCD(s):
-
Non-Biological Complex Drug(s)
- NCE:
-
New Chemical Entity
- NCL:
-
Nanotechnology Characterization Lab
- NIH:
-
National institutes of Health
- NMR:
-
Nuclear Magnetic Resonance
- NTA:
-
Nanoparticle Tracking Analysis
- PDI:
-
Polydispersity Index
- QbD:
-
Quality by Design
- ROI:
-
Region of Interest
- SAXS:
-
Small Angle X-ray Scattering
- SCC:
-
Squamous Cell Cancer
- SEC:
-
Size Exclusion Chromatography
- SmPC:
-
Summary of Product Characteristics
- SPECT:
-
Single Photon Emission Computed Tomography
- SPH:
-
Sphingomyelin
- TEM:
-
Transmission Electron Microscopy
- WHO:
-
World Health Organization
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Crommelin, D., Metselaar, J., Storm, G. (2015). Liposomes: The Science and the Regulatory Landscape. In: Crommelin, D., de Vlieger, J. (eds) Non-Biological Complex Drugs. AAPS Advances in the Pharmaceutical Sciences Series, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-16241-6_3
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