Draft Guidance for Liposomes
A new FDA draft guidance for firms that manufacture liposomal drug products offers advice on labeling, stability testing, and other aspects of the chemistry, manufacturing, and controls for those products.
The document states that any lipids used in the manufacturing of liposomes should undergo stability tests to establish storage conditions, retest dates, and shelf life. Tests for temperature, light, and oxygen resistance, as well as for pH, should be conducted to determine the degradation profile. The firm must also provide information about the container and closure system for storage and shipment of the lipids, and relevant stability data, which should address both the physical and chemical stability of the liposome drug product and of the liposome itself.
Because liposomes are a relatively new dosage form, they are not covered specifically in the 1999 guidance "Changes to an Approved NDA or ANDA," which divided potential manufacturing and packaging changes into three areas: major changes requiring prior FDA approval, moderate changes requiring only prior notice to the agency and waiting 30 days for a response, and minor changes requiring only a notation in the firm's annual report to the agency. Therefore, firms making liposomal products are asked to determine for themselves which category a change belongs to. This is done by assessing the effect of each change on the identity, strength, purity, potency, and quality of the drug as related to safety and efficacy. Comparison testing of prechange and postchange drugs should be performed initially.
Labeling should include terminology to indicate that it is a liposomal drug product. If necessary, it should also include a means to distinguish one product from other liposomal forms of the same drug substance that are not therapeutically equivalent. When warranted, a cautionary note should be included explaining that liposomal forms of drug substances can differ from nonliposomal forms. For lyophilized liposomal drug products, reconstitution instructions with supporting data must be included.
The full text of the draft guidance can be viewed at http://www.fda.gov/cder/guidance/2191dft.pdf.