Liposome drug characterisation and analysis according to FDA manufacturing and controls (CMC) Guidance including physicochemical properties, cryo-TEM, composition, encapsulation efficiency, in vitro release of the drug product and stability testing
Assessment of liposome drug product critical quality attributes (CQAs), such as physicochemical properties, composition, encapsulation efficiency and the release of drugs from the liposome formulation, and also establishing the drug product specification are all vital to drug development.
Liposomes are vesicles composed of a bilayer or multiple bilayers of amphipathic molecules such as phospholipids that encapsulate a central aqueous compartment. Robust and accurate analytical laboratory data, which addresses the requirements of the liposome FDA CMC guidance (April 2018) is necessary to support your new drug application (NDA) or abbreviated new drug application (ANDA) for a liposome drug. These recommendations should also be considered during drug development leading to the submission of an investigational new drug application (IND) for a liposome drug product. As many scientific principles described in this FDA guidance are relevant to biologics, this guidance may also apply to information required for biologics license applications (BLAs).
Liposome Drug Product Specification
The regulatory expectations for a liposomal drug product specification include a range of parameters including analysis of all components of the drug product such as the lipids, the free drug, encapsulated drug and process impurities. Our liposome team provide analytics to help you address the following:
- Physicochemical parameters determined to be CQAs (e.g. particle size, size distribution, zeta-potential and physical stability)
- Liposome contained and free drug substance
- Total drug substance content, as labelled
- Degradation products related to the lipids (e.g. lysolipids) or drug substance
- Lipid content (to demonstrate consistency with the intended formulation)
- Residual solvent(s), if any organic solvent(s) are used in the manufacture of the liposome product
- In vitro release of drug substance from the liposome drug products
Liposome Drug Encapsulation Efficiency Determination
Determination of drug encapsulation efficiency involves assessment of the amount of drug contained inside liposomes, compared with the total amount of drug and liposome drug loading (the amount of drug contained relative to the amount of lipid used). We determine the release of the drug substance the liposome product under specific conditions. Our team deploys a range of analytical approaches to drive greater understanding of liposome integrity such as drug release, drug encapsulation efficiency and drug loading in response to changes in pH, temperature, the addition of excipients, changes in salt concentration and/or interactions with components of a filtration process or manufacturing surfaces. These studies involve TEM, cryo-TEM, light microscopy, and a range of chromatographic and spectroscopic methods to determine the impact of changing environmental conditions.
Stability and Stress Testing of Liposome Drug Products
For each lipid used to manufacture the liposome we can perform stability studies and stress testing (after exposure to light, pH and oxygen) and so determine the degradation profile which we can use to establish stability-indicating analytical methods including the physicochemical properties such as particle size and size distribution. This information can help establish suitable storage conditions and retest periods.
Liposome Drug Product Regulatory Analytical Characterisation Expertise
We deliver regulatory compliant (GLP/cGMP) data from our pharmaceutical characterisation laboratory. Our scientists have experience in liposome drug analysis across a range of liposomal applications including encapsulation of small molecules or larger entities such as biologics (proteins, monoclonal antibodies) or gene therapy delivery systems. We have expertise in study design (e.g. stability studies and timepoint testing) and the development and validation of methods that are tailored to your liposome drug product characteristics. The data we generate can be used to help you establish drug product specifications, or in support of regulatory submissions such as INDs / NDAs / ANDAs or BLAs or to support your on-going quality control.
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