Method for filling vials containing liquid drug products

A method for determining a total residual volume (VHU) of a liquid drug product in a container and a withdrawal syringe, wherein VHU is determined according to equation (3):

• V
• H
• ⁢
• U
• =
• V
• H
• ⁢
• U
• w
• ⁢
• a
• ⁢
• t
• ⁢
• e
• ⁢
• r
• ×
• η
• 1
• /
• 7
• ,
• where η is the viscosity of the liquid drug product and VHUwater is a value depending on the neck diameter.

A method of predicting an excess volume (Voverfill) of a liquid drug product to be added in a container comprising the liquid drug product, the excess volume being a volume of liquid drug product required in the container in addition to a label-claim volume (Vlabel), to ensure that the label-claim volume can be withdrawn from the container, wherein the method comprises using a computer to implement:

• a) receiving a first set of values, wherein said first set of values comprises:
• i) an expected residual volume (VHU) of the liquid drug product in the container and a withdrawal syringe after dispensing of the liquid drug product from the container using the withdrawal syringe;
• ii) a total variability (σtotal) of container filling of a filling equipment to be used to fill the container with the liquid drug product, and extractable volume testing;
• iii) a predetermined tolerance factor (k);
• b) determining a predicted excess volume by performing a summation over at least VHU and k×σtotal, as shown in equation (1),
• Voverfill=VHU+k×σtotal+A
• where A represents an optional one or more further terms in the summation, and
• c) outputting the predicted excess volume to be added,
• wherein VHU is determined by:
• i) weighing an empty first container to be filled with the liquid drug product to obtain Wtare,
• ii) filling the empty first container with a given volume of the liquid drug product,
• iii) weighing the filled first container to obtain Wfull,
• iv) obtaining the weight of the liquid drug product contained in the filled first container (Wprod), wherein Wprod=Wfull−Wtare,
• v) withdrawing the liquid drug product from the filled first container with a syringe comprising a needle,
• vi) completely expelling the withdrawn liquid drug product from the syringe into a tared, clean and dry second container, without emptying the needle,
• vii) weighing the second container filled with the expelled liquid drug product to obtain a value Wextr,
• viii) determining VHU using equation (2):
• VHU=(Wprod−Wextr)/ρ, wherein the liquid drug product's density is represented by p.

A method of predicting an excess volume (Voverfill) of a liquid drug product to be added in a container comprising the liquid drug product, the excess volume being a volume of liquid drug product required in the container in addition to a label-claim volume (Vlabel), to ensure that the label-claim volume can be withdrawn from the container, wherein the method comprises using a computer to implement:

• a) receiving a first set of values, wherein said first set of values comprises:
• i) an expected residual volume (VHU) of the liquid drug product in the container and a withdrawal syringe after dispensing of the liquid drug product from the container using the withdrawal syringe;
• ii) a total variability (σtotal) of container filling of a filling equipment to be used to fill the container with the liquid drug product, and extractable volume testing;
• iii) a predetermined tolerance factor (k);
• b) determining a predicted excess volume by performing a summation over at least VHU and k×σtotal, as shown in equation (1),
• Voverfill=VHU+k×σtotal+A
• where A represents an optional one or more further terms in the summation, and
• c) outputting the predicted excess volume to be added,
• wherein VHU is determined by:
• i) filling an empty first container with a given weight of liquid drug product (Wprod),
• ii) withdrawing the liquid drug product from the filled first container with a syringe comprising a needle,
• iii) expelling the withdrawn liquid drug product from the syringe into a tared, clean and dry second container, without emptying the needle,
• iv) weighing the expelled liquid drug product in the second container to obtain a value Wextr, and
• v) determining VHU using equation (2):
• VHU=(Wprod−Wextr)/ρ, wherein the liquid drug product's density is represented by p.

A method of predicting an excess volume (Voverfill) of a liquid drug product to be added in a container comprising the liquid drug product, the excess volume being a volume of liquid drug product required in the container in addition to a label-claim volume (Vlabel), to ensure that the label-claim volume can be withdrawn from the container, wherein the method comprises:

• a) collecting a first set of values, wherein said first set of values comprises:
• i) an expected residual volume (VHU) of the liquid drug product in the container and a withdrawal syringe after dispensing of the liquid drug product from the container using the withdrawal syringe;
• ii) a total variability (σtotal) of container filling of a filling equipment to be used to fill the container with the liquid drug product, and extractable volume testing;
• iii) a predetermined tolerance factor (k);
• iv) the container neck diameter;
• v) a viscosity, n, corresponding to the viscosity of the liquid drug product;
• b) predicting the excess volume by performing a summation over at least VHU and k×σtotal, as shown in equation (1),
• Voverfill=VHU+k×σtotal+A
• where A represents an optional one or more further terms in the summation and where VHU is determined according to equation (3):
• VHU=VHUwater×η1/7, where VHUwater is a value depending on the container's neck diameter.

A method of predicting an excess volume (Voverfill) of a liquid drug product to be added in a container comprising the liquid drug product, the excess volume being a volume of liquid drug product required in the container in addition to a label-claim volume (Vlabel), to ensure that the label-claim volume can be withdrawn from the container, wherein the method comprises:

• a) collecting a first set of values, wherein said first set of values comprises:
• i) an expected residual volume (VHU) of the liquid drug product in the container and a withdrawal syringe after dispensing of the liquid drug product from the container using the withdrawal syringe;
• ii) a total variability (σtotal) of container filling of a filling equipment to be used to fill the container with the liquid drug product, and extractable volume testing;
• iii) a predetermined tolerance factor (k);
• b) predicting the excess volume by performing a summation over at least VHU and k×σtotal, as shown in equation (1),
• Voverfill=VHU+k×σtotal+A
• where A represents an optional one or more further terms in the summation, wherein VHU is determined by:
• i) filling an empty first container with a given weight of liquid drug product (Wprod),
• ii) withdrawing the liquid drug product from the filled first container with a syringe comprising a needle,
• iii) expelling the withdrawn liquid in the syringe into a tared, clean and dry second container, without emptying the needle,
• iv) weighing the expelled liquid in the second container to obtain a value Wextr,
• v) determining Vu using equation (2):
• VHU=(Wprod−Wextr)/ρ, wherein the liquid drug product's density is represented by ρ.

A method of predicting an excess volume (Voverfill) of a liquid drug product to be added in a container comprising the liquid drug product, the excess volume being a volume of liquid drug product required in the container in addition to a label-claim volume (Vlabel), to ensure that the label-claim volume can be withdrawn from the container, wherein the method comprises:

• a) collecting a first set of values, wherein said first set of values comprises:
• i) an expected residual volume (VHU) of the liquid drug product in the container and a withdrawal syringe after dispensing of the liquid drug product from the container using the withdrawal syringe;
• ii) a total variability (σtotal) of container filling of a filling equipment to be used to fill the container with the liquid drug product, and extractable volume testing;
• iii) a predetermined tolerance factor (k);
• b) predicting the excess volume by performing a summation over at least VHU and k×σtotal, as shown in equation (1),
• Voverfill=VHU+k×σtotal+A
• where A represents an optional one or more further terms in the summation and where VHU is determined by:
• i) weighing an empty first container to be filled with the liquid drug product to obtain Wtare,
• ii) filling the empty first container with a given volume of the liquid drug product,
• iii) weighing the filled first container to obtain Wfull,
• iv) obtaining the weight of the liquid drug product contained in the filled first container (Wprod), wherein Wprod=Wfull−Wtare,
• v) withdrawing the liquid drug product from the first container with a syringe comprising a needle,
• vi) completely expelling the withdrawn liquid drug product from the syringe into a tared, clean and dry second container, without emptying the needle,
• vii) weighing the second container filled with the expelled liquid drug product to obtain vii) a value Wextr, and
• viii) determining VHU using equation (2):
• VHU=(Wprod−Wextr)/ρ, wherein the liquid drug product's density is represented by ρ.