Method of filling a container with no headspace

1. A method for preparing a container with zero headspace comprising an aqueous adalimumab solution, the method comprising:

a) providing a container with an open end;

b) providing an aqueous adalimumab solution comprising about 30 mg/mL to about 50 mg/mL adalimumab and not comprising a polyol, a sugar, or a surfactant;

c) filling the container via the open end with the aqueous adalimumab solution;

d) purging the container with at least one soluble gas;

e) inserting a stopper into the open end of the container creating a headspace of soluble gas; and

f) storing the container,

wherein the stopper can move within the container while maintaining an airtight seal; and the storing step results in the container having zero headspace,

wherein, following the storing step, the aqueous adalimumab solution comprises less than about 6,000 subvisible particles having a size of ≥10 μm per 0.8 mL of the aqueous adalimumab solution and less than about 600 subvisible particles having a size of ≥25 μm per 0.8 mL of the aqueous adalimumab solution.

2. The method of claim 1 , wherein prior to the purging step or prior to inserting the stopper, the container is subjected to a pressure vacuum.

3. The method of claim 1 , wherein the soluble gas is carbon dioxide.

4. The method of claim 1 , wherein the container is stored for at least 4 hours.

5. The method of claim 1 , wherein the storing step is conducted at a temperature below the temperature at which the stoppering step occurred.

6. The method of claim 1 , comprising the steps:

a) providing a container with an open end;

b) providing an aqueous adalimumab solution;

c) filling the container via the open end with the aqueous adalimumab solution;

d) degassing the container and aqueous adalimumab solution via a pressure vacuum;

e) purging the container with at least one soluble gas;

f) optionally repeating the degassing and purging steps;

g) degassing via a pressure vacuum and while under vacuum, inserting a stopper into the open end of the container creating a headspace of soluble gas; and

h) storing the container.

7. The method of claim 1 , wherein the container is a syringe or a cartridge.

8. The method of claim 1 , wherein the aqueous drug substance solution is further free or substantially free of buffer, salt, stabilizer, or any combination thereof.