Etanercept formulations stabilized with metal ions
The invention provides stabilized aqueous pharmaceutical etanercept compositions suitable for long-term storage of etanercept, methods of manufacture of these compositions, methods of administration, and kits containing same.
1. An aqueous pharmaceutical composition containing no arginine, the composition comprising about 50 mg/mL etanercept, a buffer, and a stabilizer comprising 5 to 10 mM magnesium chloride or 2 to 10 mM calcium chloride, wherein the composition has a pH of about 6.0 to 6.6 and is stable such that the composition has less than 1 wt % aggregate content by size exclusion chromatography (SEC) for one month at 5° C.
2. The composition of claim 1 , wherein the osmolality of the composition is from about 180 to about 420 mOsM.
3. The composition of claim 1 , wherein the composition is suitable for subcutaneous administration as a flat dose and the dose contains about 10-80 mg etanercept.
4. The composition of claim 1 having, on average, no more than 10,000 subvisible particles per mL having a size greater than 5 μm.
5. The composition of claim 1 further comprising a tonicity modifier.
6. The composition of claim 5 , wherein the osmolality of the composition is from about 180 to about 420 mOsM.
7. The composition of claim 5 , wherein the composition is suitable for subcutaneous administration as a flat dose and the dose contains about 10-80 mg etanercept.
8. The composition of claim 1 , further characterized in that the composition is stable such that the composition has less than 1 wt % aggregate content measured by size exclusion chromatography (SEC) for 4 weeks at 25° C.
9. The composition of claim 1 , further characterized in that the composition is stable such that the composition has less than 1 wt % aggregate content measured by size exclusion chromatography (SEC) for up to two months at 25° C.
10. The composition of claim 1 , comprising 100 mM or less sodium chloride.