Method of optimizing a filling recipe for a drug container

Abstract

A method of filing a vial. The method includes providing a pump corresponding to a vial and setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees. The method also includes setting a no adjustment limit for a fill weight of the vial to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight T0, wherein a process performance index Cpk (Cpk) for the vial throughout a fil cycle exceeds a minimum value.

1 . A method of filling a vial, the method comprising:
 providing a pump corresponding to a vial;   setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees; and   setting a no adjustment limit for a fill weight of the vial to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight T0;   wherein a process performance index Cpk (Cpk) for the vial throughout a fill cycle exceeds a minimum value.   
     
     
         2 . The method of  claim 1 , wherein setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees comprises setting the drip retraction parameter for the pump to one of 10 degrees, 20 degrees, or any value in a range of 10 degrees to 20 degrees. 
     
     
         3 . The method of  claim 1 , further comprising setting an end drip retraction value to 290 degrees when setting the drip retraction parameter to 20 degrees or setting an end drip retraction value to 280 degrees when setting the drip retraction parameter to 10 degrees. 
     
     
         4 . The method of  claim 1 , wherein providing a pump corresponding to a vial comprises providing a pump corresponding to a vial of a nested syringe and vial line. 
     
     
         5 . The method of  claim 1 , wherein providing a pump corresponding to a vial comprises providing one or more of a first fill set or a second fill set, the first fill set including a peristaltic pump filling assembly having a needle with an outer diameter of about 2.0 mm, and the second fill set including a peristaltic pump filling assembly having a needle with an outer diameter of about 3.0 mm. 
     
     
         6 . The method of  claim 1 , wherein a Cpk for the vial exceeds a minimum value throughout a fill cycle comprises one or more of:
 (1) the Cpk for the vial exceeds a value of 1.33; or (2) the Cpk for the vial exceeds the minimum value during a temperature range throughout the fill cycle, the temperature range one of: (1) 5 (+/−3) degrees Celsius; (2) 20 (+/−5) degrees Celsius; or (3) 10 to 19 degrees Celsius.   
     
     
         7 . The method of  claim 1 , further comprising filling the vial with a drug product via the pump, wherein the drug product has one or more of the following characteristics: (a) a density in a range of about 1.0-1.2 g/cm 3 ; (b) a viscosity in a range of about 1.0-10.0 cP; and (c) a surface tension in a range of about 40.0-72.7 mN/m, and wherein at least one of the drug product has a density in a range of about 1.0-1.2 g/cm 3 ; a viscosity in a range of about 1.0-10.0 cP, and a surface tension in a range of about 40.0-72.7 mN/m, or the drug product comprises a small molecule drug or a biologic drug. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . A method of filling a plurality of vials of a nested syringe and vial line, the method comprising:
 providing a plurality of pumps corresponding to a plurality of vials of a nested syringe and vial line;   setting a drip retraction parameter for each pump in the plurality of pumps to any value equal to or less than 20 degrees; and   filling each vial of the plurality of vials with a drug product via a corresponding pump of the plurality of pumps; and   wherein a process performance index (Cpk) for each vial of the plurality of vials throughout a fill cycle exceeds a minimum value.   
     
     
         11 . The method of  claim 10 , further comprising at least one of: (1) setting a no adjustment limit for a fill weight of each vial to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight T0; or (2) setting an end drip retraction value to 290 degrees when setting the drip retraction parameter to 20 degrees or setting an end drip retraction value to 280 degrees when setting the drip retraction parameter to 10 degrees. 
     
     
         12 . The method of  claim 10 , wherein at least one of: (1) setting a drip retraction parameter for each pump to any value equal to or less than 20 degrees comprises setting the drip retraction parameter for the pump to one of 10 degrees, 20 degrees, or any value in a range of 10 degrees to 20 degrees; or (2) filling each vial of the plurality of vials with a drug product via a corresponding pump of the plurality of pumps comprises filling each vial of the plurality of vials with a mAb formulation drug product. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 10 , wherein a Cpk for each vial of the plurality of vials exceeds a minimum value throughout a fill cycle comprises one or more of: (1) the Cpk exceeds a value of 1.33; or (2) the Cpk for each vial of the plurality of vials exceeds the minimum value during a temperature range throughout the fill cycle, the temperature range one of: (1) 5 (+/−3) degrees Celsius; (2)  20  (+/−5) degrees Celsius; or (3) 10 to 19 degrees Celsius. 
     
     
         16 . The method of  claim 10 , wherein filling each vial with a drug product via a corresponding pump of the plurality of pumps comprises filling each vial with a drug product via the pump, wherein the drug product has one or more of the following characteristics: (1) a density in a range of about 1.0-1.2 g/cm 3 ; (2) a viscosity in a range of about 1.0-10.0 cP; and/or (3) a surface tension in a range of about 40.0-72.7 mN/m, and wherein at least one of the drug product has a density in a range of about 1.0-1.2 g/cm 3 ; a viscosity in a range of about 1.0-10.0 cP; and a surface tension in a range of about 40.0-72.7 mN/m or the drug product comprises a biologic drug or a small molecule drug. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A method of optimizing a filling recipe for a nested syringe and vial line, the method comprising:
 setting a drip retraction parameter for at least one pump in an offline manufacturing system corresponding to at least one container to any value equal to or less than 20 degrees;   monitoring a performance of the at least one pump with the drip retraction parameter of the at least one pump set to any value equal to or less than 20 degrees;   obtaining at least a minimum value for a process performance index (Cpk) for the at least one container throughout at least one fill cycle and for at least one drug product using the at least one pump in the offline manufacturing system; and   finalizing a filling recipe for a nested syringe and vial line using data from fill cycles of the at least one drug product using the at least one pump in the offline manufacturing system.   
     
     
         20 . The method of  claim 19 , further comprising monitoring a performance of the filling recipe in the nested syringe and vial line and obtaining at least a minimum value for the Cpk for the at least one container for each pump in a plurality of pumps in the nested syringe and vial line. 
     
     
         21 . The method of  claim 19 , wherein setting a drip retraction parameter for at least one pump in an offline manufacturing system corresponding to at least one container to any value equal to or less than 20 degrees comprises setting the drip retraction parameter for a first fill set including a pump and a second fill set including a pump, each of the first and second fill sets in the offline manufacturing system, each of the first fill set and the second fill set having a corresponding filling container. 
     
     
         22 . The method of  claim 19 , wherein obtaining at least a minimum value for a Cpk for the container throughout at least one fill cycle and for at least one drug product comprises at least one of: (1) obtaining at least a minimum value for the Cpk of 1.33 for each container during a temperature of one or more of 5 (+/−3) degrees Celsius, 20 (+− 5 ) degrees Celsius, or any value in a range of 10 degrees to 20 degrees Celsius throughout a fill cycle, the minimum value for the Cpk being 1.33 for each container; or (2) obtaining at least a minimum value for a Cpk for the container throughout at least one fill cycle and for the at least one drug product, the at least one drug product including one or more of: (1) a mAb formulation; or (2) a drug product having one or more of: (a) a density in a range of about 1.0-1.2 g/cm 3 : (b) a viscosity in a range of about 1.0-10.0 cP; and (c) a surface tension in a range of about 40.0-72.7 mN/m. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 19 , after setting the drip retraction parameter for the at least one pump in the offline manufacturing system, further comprising filling the at least one container with a drug product via the at least one pump, wherein filling the container with a drug product via the at least one pump comprises filling the container with a drug product including one or more of: (1) a mAb formulation; or (2) a drug product having one or more of: (a) a density in a range of about 1.0-1.2 g/cm 3 ; (b) a viscosity in a range of about 1.0-10.0 cP; and (c) a surface tension in a range of about 40.0-72.7 mN/m. 
     
     
         25 . The method of  claim 19 , further comprising at least one of: (1) setting a no adjustment limit for a fill weight of the container to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight T0 after setting the drip retraction parameter; or (2) one or more of: setting a start pump dosing to 40 degrees, setting a pump dosing start ramp to 90 degrees, setting a pump dosing stop ramp to 210 degrees, setting an end pump dosing to 260 degrees, setting an end drip retraction parameter to 290 degrees, and setting a distance run per dose parameter to 766 degrees. 
     
     
         26 . (canceled) 
     
     
         27 . A method of filling a vial, the method comprising:
 providing a pump corresponding to a vial;   setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees; and   setting a no adjustment limit for a fill weight of the vial to any value within a range of a target fill weight T0 and T1, with T1 being at or in a range between the target fill weight T0 and T2,   wherein a minimum value for a process performance index Cpk (Cpk) for the vial throughout a fill cycle is exceeded.   
     
     
         28 . The method of  claim 27 , wherein setting a drip retraction parameter for the pump to any value equal to or less than 20 degrees comprises setting the drip retraction parameter for the pump to one of 10 degrees, 20 degrees, or any value in a range of 10 degrees to 20 degrees. 
     
     
         29 . The method of  claim 27 , further comprising at least one of: (1) setting an end drip retraction value to 290 degrees when setting the drip retraction parameter to 20 degrees or setting an end drip retraction value to 280 degrees when setting the drip retraction parameter to 10 degrees; or (2) filling the vial with a drug product via the pump, wherein filling the vial with a drug product via the pump comprises filling the vial with a drug product including one or more of: (1) a density in a range of about 1.0-1.2 g/cm 3 ; and/or (2) a viscosity in a range of about 1.0-10.0 cP; and/or (3) a surface tension in a range of about 40.0-72.7 mN/m. 
     
     
         30 . The method of  claim 27 , wherein providing a pump corresponding to a vial comprises at least one of: (1) providing a pump corresponding to a vial of a nested syringe and vial line; or (2) providing one or more of a first fill set or a second fill set, the first fill set including a peristaltic pump filling assembly having a needle with an outer diameter of about 2.0 mm, and the second fill set including a peristaltic pump filling assembly having a needle with an outer diameter of about 3.0 mm. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 27 , wherein a Cpk for the vial exceeds a minimum value throughout a fill cycle comprises one or more of: (1) the Cpk for the vial exceeds a value of 1.33; or (2) the Cpk for the vial exceeds the minimum value during a temperature range throughout the fill cycle, the temperature range one of: (1) 5 (+/−3) degrees Celsius; (2) 20 (+/−5) degrees Celsius; or (3) 10 to 19 degrees Celsius. 
     
     
         33 . (canceled)