END POINT DETECTION FOR LYOPHILIZATION
Methods and systems for endpoint detection of lyophilization processes are provided. A method for detecting an endpoint in a lyophilization process includes monitoring a total pressure of gases within a chamber containing a sample undergoing lyophilization and controlling a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber. The method further includes determining that sufficient water has been removed from the chamber based on total pressure and mass flow rate of inert gas being delivered.
1 . A method of determining an endpoint in a lyophilization process, comprising:
monitoring a total pressure of gases within a chamber containing a sample undergoing lyophilization;
controlling a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber; and
determining that sufficient water has been removed from the chamber based on total pressure and mass flow rate of inert gas being delivered.
2 . The method of claim 1 , wherein determining that sufficient water has been removed from the chamber comprises determining a change in the mass flow rate of inert gas being delivered to the chamber and that the change has fallen beneath a threshold value.
3 . The method of claim 1 , wherein determining that sufficient water has been removed from the chamber comprises determining a partial pressure P H2O of water vapor in the chamber and that the partial pressure P H2O of water vapor in the chamber has fallen beneath a threshold value.
4 . The method of claim 3 , further comprising determining a partial pressure P H2O of water vapor in the chamber according to the following:
P
H
2
O
=
P
T
-
Q
S
where P T is the total pressure, Q is the mass rate of flow of inert gas delivered to the chamber, and S is a volume rate of flow of inert gas being removed from the chamber.
5 . The method of claim 4 further comprising:
supplying inert gas to the chamber; and
determining the volume rate of flow S of inert gas being removed from the chamber according to the following:
S
=
Q
R
P
R
where P R is a reference pressure and Q R is a mass rate of flow of inert gas delivered to the chamber at the reference pressure.
6 . The method of claim 1 , further comprising maintaining a volume rate of flow of inert gas being removed from the chamber at a constant value during lyophilization.
7 . The method of claim 1 , further comprising controlling the mass rate of flow of inert gas delivered to the chamber to maintain the total pressure of gases within the chamber at a constant value during lyophilization.
8 . The method of claim 1 , wherein the inert gas is non-condensable.
9 . A system for determining an endpoint in a lyophilization process, comprising:
a sensor that monitors a total pressure of gases within a chamber containing a sample undergoing lyophilization;
a mass flow controller that controls a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber; and
a controller configured to determine that sufficient water has been removed from the chamber based on total pressure and mass flow rate of inert gas being delivered.
10 . The system of claim 9 , wherein the controller is further configured to determine a change in the mass flow rate of inert gas being delivered to the chamber and that the change has fallen beneath a threshold value for sufficient water having been removed from the chamber.
11 . The system of claim 9 , wherein the controller is further configured to determine a partial pressure P H2O of water vapor in the chamber and that the partial pressure P H2O of water vapor in the chamber has fallen beneath a threshold value for sufficient water having been removed from the chamber.
12 . The system of claim 11 , wherein the controller is further configured to calculate a partial pressure P H2O of water vapor in the chamber according to the following:
P
H
2
O
=
P
T
-
Q
S
where P T is the total pressure, Q is the mass rate of flow of inert gas delivered to the chamber, and S is a volume rate of flow of inert gas being removed from the chamber.
13 . The system of claim 12 , wherein the controller is further configured to:
supply inert gas to the chamber; and
calculate the volume rate of flow S of inert gas being removed from the chamber according to the following:
S
=
Q
R
P
R
where P R is a reference pressure and Q R is a mass rate of flow of inert gas delivered to the chamber at the reference pressure.
14 . The system of claim 9 , wherein the sensor is a capacitance diaphragm gauge.
15 . The system of claim 9 , wherein the vacuum pump maintains a volume rate of flow of inert gas being removed from the chamber at a constant value during lyophilization.
16 . The system of claim 9 , wherein the controller is further configured to control the mass rate of flow of inert gas delivered to the chamber to maintain the total pressure of gases within the chamber at a constant value during lyophilization.
17 . The system of claim 9 , wherein the inert gas is non-condensable.
18 . The system of claim 9 , wherein the controller is further configured to display a percentage of the total pressure due to water vapor.
19 . The system of claim 9 wherein the controller is further configured to display the total pressure and the mass flow rate of inert gas delivered to the chamber.
20 . A method of detecting water content during a lyophilization process, comprising:
monitoring a total pressure of gases within a chamber containing a sample undergoing lyophilization;
controlling a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber; and
determining a water content in the chamber based on total pressure and mass flow rate of inert gas being delivered.
21 . A lyophilization process, comprising:
monitoring a total pressure of gases within a chamber containing a sample undergoing lyophilization;
removing water vapor from the chamber with a water pump;
controlling a mass rate of flow of inert gas delivered to the chamber to replace water removed from the chamber;
pumping inert gas from the chamber with a vacuum pump;
determining that sufficient water has been removed from the chamber based on total pressure and mass flow rate of inert gas being delivered; and
ending the lyophilization process when sufficient water has been removed.
22 . A system for detecting water content during a lyophilization process, comprising:
a sensor that monitors a total pressure of gases within a chamber containing a sample undergoing lyophilization;
a mass flow controller that controls a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber; and
a controller configured to determine a water content in the chamber based on total pressure and mass flow rate of inert gas being delivered.
23 . A lyophilization system, comprising:
a sensor that monitors a total pressure of gases within a chamber containing a sample undergoing lyophilization;
a water pump that removes water vapor from the chamber;
a mass flow controller that controls a mass rate of flow of inert gas delivered to the chamber to replace water vapor removed from the chamber;
a vacuum pump that pumps inert gas from the chamber; and
a controller configured to:
determine that sufficient water has been removed from the chamber based on total pressure and mass flow rate of inert gas being delivered, and
end the lyophilization process when sufficient water has been removed.