Extended Release Formulations and Devices

New delivery systems, including devices that provided extended, controlled release of rHuEPO, could allow for smooth, sustained stimulation of erythropoiesis. Such devices necessitate that the molecule remain stable for a prolonged period. Another approach could be to introduce rHuEPO into a slow-release, biodegradable matrix that would erode at a predictable rate and release the protein in a controlled manner (152,153).

To date, no slow-release process has been successful. The requirement for protein stability both during manufacturing and when implanted in the body has been a challenge, particularly when considering biodegradable matrices. Small amounts of contaminating rHuEPO aggregates, misfolded rHuEPO, or breakdown products would probably compromise not only efficacy but also safety (immunogenicity). Another concern is that too rapid breakdown of the matrix might result in an overdose of rHuEPO.

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