By: Mustafa A. Zaman, Principal Consultant, PAREXEL® Consulting
In April 2018, FDA published guidance on the complex theme of ‘’Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation’’
Liposomes are vesicles composed of a bilayer (uni-lamellar) and/or a concentric series of multiple bilayers (multi-lamellar) separated by aqueous compartments. In a liposome drug product, the drug substance is generally encapsulated in the liposome. Release of drugs from liposome formulations, among other characteristics such as liposomal clearance and circulation half-life, can be modified by the presence of excipients (e.g. polyethylene glycol and/or cholesterol) or other potential additives in the liposome.
Development of such drug delivery systems to improve disease-specific targeting, control drug release rates and/or to produce a pharmaceutical formulation suitable for clinical use, is highly desirable.
The FDA’s guidance finalizes the revised draft guidance (published in October 2015), and outlines what types of information applicants should submit in each new drug application (NDA) or abbreviated new drug application (ANDA) for a liposome drug product reviewed by the Center for Drug Evaluation and Research (CDER). It also provides useful information on how to approach the following topics for liposome drug products:
- Chemistry, Manufacturing, and Controls (CMC);
- Human Pharmacokinetics and Bioavailability or, in the case of an ANDA, Bioequivalence; and
- Labelling in NDAs and ANDAs.
It is noteworthy that there is also a European Union (EU) reflection paper on the data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. This paper outlines the critical and relevant quality, non-clinical and clinical data to support a marketing authorization of intravenous liposomal products developed with reference to an Innovator/Reference Listed Drug (RLD) liposomal product.
PAREXEL is currently supporting clients in developing regulatory strategies and submissions for a variety small molecule products, which take into account focal points such as the Physicochemical Properties, Comparability to RLD, Manufacturing Process Controls, Critical Quality Attributes, Human Pharmacokinetics and/or Bioavailability Studies and Life Cycle Management.