Stable aqueous formulations of adalimumab
The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.
1. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) a buffer, wherein the buffer is present in the composition at a concentration of less than 50 mM;
c) an amino acid, wherein the amino acid is present in the composition at a concentration of up to about 300 mM; and
d) about 0.01 wt % to about 0.2 wt % of a surfactant;
wherein the composition is free of i) mannitol, ii) citrate and phosphate buffers, and iii) sodium chloride, and wherein the composition has a pH of about 5 to about 6, and is stable at 40° C. for one week or at 25° C. for two weeks.
2. The composition of claim 1 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
3. The composition of claim 1 , wherein the pH is about 5.2.
4. The composition of claim 3 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
5. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) a buffer, wherein the buffer is present in the composition at a concentration of less than 50 mM;
c) an amino acid selected from glycine, arginine, methionine, and combinations thereof, wherein the amino acid is present in the composition at a concentration of up to about 300 mM; and
d) about 0.01 wt % to about 0.2 wt % of a surfactant;
wherein the composition is free of i) mannitol, ii) citrate and phosphate buffers, and iii) sodium chloride, and wherein the composition has a pH of about 5 to about 6, and is stable at 40° C. for one week or at 25° C. for two weeks.
6. The composition of claim 5 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
7. The composition of claim 5 , wherein the pH is about 5.2.
8. The composition of claim 7 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
9. The composition of claim 5 , wherein the amino acid is methionine.
10. The composition of claim 9 , wherein the pH is about 5.2.
11. The composition of claim 10 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
12. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) a buffer, wherein the buffer is present in the composition at a concentration of less than 50 mM;
c) an amino acid, wherein the amino acid is present in the composition at a concentration of up to about 300 mM; and
d) about 0.01 wt % to about 0.2 wt % of polysorbate 80;
wherein the composition is free of i) mannitol, ii) citrate and phosphate buffers, and iii) sodium chloride and wherein the composition has a pH of about 5 to about 6, and is stable at 40° C. for one week or at 25° C. for two weeks.
13. The composition of claim 12 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
14. The composition of claim 12 , wherein the pH is about 5.2.
15. The composition of claim 14 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
16. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) a buffer, wherein the buffer is present in the composition at a concentration of less than 50 mM;
c) an amino acid selected from glycine, arginine, methionine, and combinations thereof, wherein the amino acid is present in the composition at a concentration of up to about 300 mM; and
d) about 0.01 wt % to about 0.2 wt % polysorbate 80;
wherein the composition is free of i) mannitol, ii) citrate and phosphate buffers, and iii) sodium chloride, and wherein the composition has a pH of about 5 to about 6, and is stable at 40° C. for one week or at 25° C. for two weeks.
17. The composition of claim 16 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
18. The composition of claim 16 , wherein the pH is about 5.2.
19. The composition of claim 18 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
20. The composition of claim 16 , wherein the amino acid is methionine.
21. The composition of claim 20 , wherein the pH is about 5.2.
22. The composition of claim 21 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.