The Development of a Novel Aflibercept Formulation for Ocular Delivery

Area of Science:

• Ophthalmology
• Biopharmaceutical Formulation
• Protein Chemistry

Background:

• Aflibercept is a critical biologic therapy for numerous ocular conditions.
• Current formulations require strict cold chain storage, limiting global accessibility.
• Thermostability is a key challenge for biopharmaceutical drug products.

Purpose of the Study:

• To develop and evaluate alternative liquid formulations of aflibercept for ocular delivery.
• To enhance the thermostability of aflibercept formulations.
• To enable potential storage outside the cold chain, particularly for low to middle-income countries.

Main Methods:

• Investigated effects of pH, stabilizers (amino acids vs. sucrose/salt), and surfactants (poloxamer 188 vs. polysorbate 20).
• Assessed aggregate formation at various temperatures (4°C, 30°C, 40°C).
• Evaluated subvisible particles, post-translational modifications (multi-attribute method), purity (capillary electrophoresis), and potency (cell proliferation).

Main Results:

• A formulation with acetate, proline, and poloxamer 188 exhibited reduced aggregate formation compared to the commercial standard.
• The enhanced formulation demonstrated comparable or improved stability under transport stress and long-term 4°C storage.
• Analytical characterization confirmed comparable purity, post-translational modifications, and potency.

Conclusions:

• An alternative aflibercept formulation using acetate, proline, and poloxamer 188 shows enhanced thermostability.
• This improved stability may permit limited storage outside the cold chain.
• Facilitates broader distribution of aflibercept, especially in resource-limited settings.