Process for aseptic vacuum filling and stoppering of low viscosity liquids in syringes
A process and method by which low viscosities liquids are filled into syringes without gas bubbles utilizing lowered temperature and valves to isolate the filling system from the vacuum. The liquid may be drug, device, pharmaceutical, and/or biotech products.
1 . A process for removing gas bubbles, the process comprising filling containers under aseptic conditions with sterile fluid; and stoppering the containers, wherein filling and stoppering steps are performed under a vacuum utilizing check valves to isolate fill lines, and lowered temperature to suppress vapor pressure of the fluid being filled.
2 . The process according to claim 1 , wherein the lowered temperature is obtained by a procedure selected from at least one of, cooling product feed into filling pumps, placing an in-line chiller on the filling pumps, placing an in-line chiller on the fill lines, reducing filling room temperature, chilling the containers on-line with a cold gas, and pre-chilling the contains.
3 . The process according to claim 1 , further comprising, prior to filling the containers, applying a pre-vacuum.
4 . The process according to claim 1 , wherein the gas bubbles comprise air.
5 . The process according to claim 1 , wherein the gas bubbles comprise a gas other than air.
6 . The process according to claim 1 , wherein the extent of the vacuum is at least about 28 inches of mercury and the temperature is less than about 8 C.
7 . The process according to claim 1 , wherein the extent of the vacuum is at least about 29 inches of mercury and the temperature is less than about 8 C.
8 . The process according to claim 1 , wherein the volume of the fluid is about 0.01 ml to about 100 ml.
9 . The process according to claim 1 , further comprising prior to filling, sterilizing the fluid by filter sterilization.
10 . The process according to claim 1 , wherein the filling and stoppering is automated.
11 . The process according to claim 10 , wherein the automated process is high-throughput.
12 . The process according to claim 1 , wherein the containers are selected from at least one of the group of vials, hypodermic syringes, bottles, cartridges, and capsules.
13 . The process according to claim 1 , wherein the fluid comprises a product selected from at least one of a protein, polymer, a polysaccharide, a vaccine, an anti-serum, a mucoprotein, a nucleic acid, and a lipoprotein.
14 . The process according to claim 13 , wherein the product is recombinantly produced.
15 . An article of manufacture comprising a fluid in an aseptically filled and stoppered container prepared by the method of filling the container under aseptic conditions with sterile fluid and stoppering the containers, wherein filling and/or stoppering steps are performed under a vacuum.
16 . The article of manufacture according to claim 15 , wherein the amount of the vacuum is at least about 28 inches of mercury.
17 . The article of manufacture according to claim 15 , wherein the fluid further comprises a pharmaceutically acceptable buffer or salt.
18 . The article of manufacture according to claim 15 , wherein the fluid is primarily aqueous.