This is a summary of colleague experiences regarding residual pressure in a lyophilized products specifically to answer the following questions:
1) What range of reduced pressure have you seen in your work? Do you use only enough to ensure stopper placement?
2) Have you encountered products having reduced pressure to aid in reconstitution? Have you seen vials stoppered under "full" vacuum?
3) What methods are used to measure vial pressure?
1) Residual Vial Pressure
The majority of my colleagues state they have seen residual vial pressure of about 10 psi (average of 10.7 +_ 1.8 psi (not including 14.4 psi data point), however, one respondent stated their company uses only enough reduced pressure to help seat the stoppers (14.4 psi). Another respondent stated stoppering at atmospheric pressure is acceptable, however, I believe this actually means a slightly reduced pressure (14.4 psi). If stoppers are seated at atmospheric pressure it can be common to have the stopper “pop up when removed from the freeze dryer ” thus breaking the seal. The temperature affects the pressure.
Very few respondents were aware of vials having a very low residual pressure typically referred to as “full vacuum”. Out-gassing of the stopper is a concern with reduced residual pressure; however, even though this may be true I have not yet found a reference to support this concern.
Container Closure studies must be performed to confirm the stopper – vial seal remains intact. It most do not measure the pressure within the vials.
The pressure is obtained by stoppering in the freeze dry chamber at the selected value as indicated on the freeze drier pressure gauges.
9.67 to 11.61 psi
14.41 psi
7.35 psi
11.61 to 13.08 psi
10.88 psi
Conversion chart for your information
http://www.onlineconversion.com/pressure.htm
1 atmosphere (standard)
29.92 Inches Hg
760 Torr
14.7 PSI
1.014 Bar
2) Reduced pressure to aid recon.
None of the respondent indicated they purposely reduce the pressure within the vial to facilitate product reconstitution, however, most commented a reduce pressure could help with product reconstitution.
Very few respondents were aware of vials having a very low residual pressure typically referred to as “full vacuum”.
3) Methods to Measure Pressure
There are several methods to measure pressure within a vial.
The Spark Test is not quantitative and has a threshold pressure where a spark will not be observed. Damage to the product should be considered
The use of a Bourdon or Diaphragm gauge with needle to puncture the vial can be accurate and precise. Calibration is necessary, which can be performed but may be “tricky”. This is a destructive test.
The Lighthouse Instrument measures vial headspace gases, however, the company suggests reduced pressure (vacuum) can be determined. I have experience with the headspace measurement, which was accurate, but no experience with the determination of reduced pressure. This is a nondestructive test.