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Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation

FinalCenter for Drug Evaluation and Research04/05/2018

Description

This guidance discusses what types of information you, the applicant, should submit in your 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). The discussion addresses the following topics for liposome drug products: (A) chemistry, manufacturing, and controls (CMC); (B) human pharmacokinetics and bioavailability or, in the case of an ANDA, bioequivalence; and (C) labeling in NDAs and ANDAs.

Scope & Applicability

Product Classes

2
Liposome Drug Products

specific product type mentioned in table of contents; Specific guidance for dosage and administration

Liposome Drug Product

Substitution recommendations

Stakeholders

1
Applicant

Entity submitting development data and knowledge; Entity performing the work process for change

Regulatory Context

Attributes

7
Critical Quality Attributes

Physical, chemical, biological, or microbiological properties

Therapeutically equivalent

determination by FDA regarding substitution

Molar ratio

Molar ratio of each individual lipid to the drug substance.

Morphology

Physicochemical property including lamellarity determination.

Zeta potential

Surface charge attribute impacting stability

Particle size

Physical property of drug substance affecting manufacturability

Mean particle size

Physicochemical parameters of the liposome determined to be the CQAs.

Identified Hazards

Hazards

3
Bacterial endotoxins

risk of febrile reaction addressed by pyrogenicity testing

Dose dumping

potential cause of product failure in sustained-release dosage forms

Oxidative degradation

Lipids with unsaturated fatty acids are subject to oxidative degradation.

Related CFR Sections (5)

See Also (8)