Field of the Invention
[0001] The present invention relates generally to a freeze drying process for
removing moisture from a product using vacuum and low temperature. More
specifically, the invention relates to the problem of monitoring process parameters
before, during and after the freeze drying operation is performed.
Background
[0002] Freeze drying is a process that removes a solvent, typically water, from a
product in the form of ice. While water is used in the present disclosure as the exemplary
solvent, other solvents, such as alcohol, are also used in freeze drying processes and may
be used with the presently disclosed methods and apparatus. In the freeze drying process,
the product is frozen and, under vacuum, the ice sublimes and the vapor flows towards a
condenser. The water or other solvent is condensed on the condenser as ice and is
removed in a later stage. Freeze drying is particularly useful in the pharmaceutical
industry, as the integrity of the product is preserved during the freeze drying process and
product stability can be guaranteed over relatively long periods of time. The freeze dried
product is ordinarily a biological substance and is commonly contained in vials.
[0003] As illustrated by the example freeze drying system 100 of FIG. 1, a batch
of product 112 is placed on freeze dryer shelves 121 within a freeze drying chamber 110.
The freeze dryer shelves 121 are hollow and are used to support the product and to
transfer heat to and from the product as required by the process. A heat transfer fluid 114
flows through the shelves to remove or add heat.
[0004] Water vapor created by the sublimation of ice in the product 112 flows
through a passageway 115 into a condensing chamber 120 containing condensing coils or
other surfaces 122 maintained below the condensation temperature. A coolant 125 is
passed through the coils 122 to remove heat, causing the water vapor to condense as ice
on the coils.
[0005] Both the freeze drying chamber 110 and the condensing chamber 120 are
maintained under vacuum during the process by a vacuum pump 150 having a low
pressure inlet 151 connected to the exhaust of the condensing chamber 120. Noncondensable
gases contained in the chambers 110, 120 are removed by the vacuum pump
150 and exhausted at a high pressure outlet 1 2.
[0006] Pharmaceutical freeze drying is an aseptic process that requires sterile
conditions within the freeze drying chamber 110 and condenser chamber 120. A freeze
drying cycle may last several days, and the quantity of product processed in a single
batch may represent a very large investment. It is therefore critical to assure that the
freeze drying system is sterile and leak-free before a cycle is commenced and for the
duration of the cycle. Both the shelves in the freeze drying chamber and the coils in the
condensing chamber are hollow, and contain heat transfer media. It is important to be
able to detect any leakage of those non-sterile fluids into the process vessels should a leak
occur.
[0007] In the condenser, the coolant media used may be of a very low viscosity,
and have a low vapor pressure, making detection of a leak difficult. In the case of a
condenser circuit that is cooled by direct expansion of a refrigerant, leakage of the
gaseous refrigerant is also difficult to detect and is undesirable in the freeze drying
process. In the freeze drying chamber, the hollow shelves are flushed by thermal fluid
that is typically a silicone oil of very low viscosity. Those silicone oils also have a very
low vapor pressure, making it very difficult to detect leakage. Therefore there is a need
for leak detection, preferably real time, without disturbing the aseptic freeze drying
process.
[0008] The chambers and connecting passages are under vacuum and are
therefore required to maintain a high pressure differential across their walls. Any leakage
of non-sterile ambient gases through the walls into the aseptic chambers must be detected
as quickly and accurately as possible.
[0009] It has been proposed to perform a secondary drying operation wherein the
condensing chamber 120 is temporarily bypassed by a passageway 130 in a final drying
stage to remove small amounts of residual moisture. In the secondary drying operation, a
small amount of residual water vapor from the product passes through the vacuum pump
150 and is contained in the vacuum pump exhaust. The secondary drying process is
conceptually limited by the capacity of the vacuum pump to pump water vapor. One
expected problem in performing a secondary drying operation is the adequate detection or
measurement of moisture content in the product, for monitoring the progress of the
operation. A system is needed for measuring water removal without interfering with the
pharmaceutical drying process.
[0010] Most freeze dryer diagnostic techniques are direct, and analyze the
condition of the gas in the drying chamber. Direct checking of leakage may be
complicated with very large freeze dryers, where manual checking cannot be done.
Further, if the leakage is related to certain time periods in the freeze-drying cycle, or
related to certain high or low temperatures, the likelihood of detection might be minimal.
[0011] Examples of such in-situ low pressure analysis techniques are residual gas
analysis using mass spectroscopy, and partial pressure gas analysis, for which there are
many specialized methods. Several disadvantages are inherent in those technologies.
The measurements of interest are taken at low pressure, meaning low concentrations that
result in detection difficulties. Moreover, the gas streams within the freeze drying
chamber and the condensation chamber contain a large amount of water (99%) from the
drying process, which may overwhelm the measurement of other species.
[0012] The measurement technologies may interfere with the drying process.
Those in-situ low-pressure detection technologies must, by nature, sample the gas flow
within the sterile environment where freeze drying takes place. Many of those
technologies, however, involve sensors that are not easily sterilized. Some of those
technologies even create byproducts such as chemically reactive species that may affect
the material that is being dried in unfavorable ways.
[0013] There is therefore a need for a technique for effectively monitoring a
freeze drying process without disturbing the normal process routine. The technique
should be easily automated, should not introduce contaminants into the process, and
should detect, with high accuracy, leaks or other abnormalities in the process.
Summary
[0014] The present disclosure addresses the needs described above by providing a
method for analyzing a gas stream containing a solvent vapor. In the method, the solvent
vapor is first removed from the gas stream to produce a non-condensable gas stream. The
non-condensable gas stream is compressed to produce a compressed gas stream. A
concentration of a material is then measured in the compressed gas stream.
[0015] The gas stream containing the solvent vapor may be an exhaust from a
freeze drying chamber. The freeze drying chamber may include hollow freeze drying
shelves containing a heat transfer fluid, in which case the material measured in the
compressed gas stream is heat transfer fluid leaking from the shelves. The heat transfer
fluid may contain a perfluorinated fluid, in which case a concentration of the
perfluorinated fluid is measured using a halogen leak detector.
[0016] The step of removing the solvent vapor from the gas stream may include
passing the gas stream through a condensation chamber containing cooled condensing
surfaces. In that case, the measured material may be a medium for cooling the
condensing surfaces that is leaking into the condensation chamber.
[0017] The measured material may be a residual cleaning material used in
cleaning a process chamber. The cleaning material may be hydrogen peroxide (H20 2) or
chlorine dioxide (C102).
[0018] The measurement step may include using acousto-optic spectrometry to
measure the concentration of the material. The measurement step may include using a
measurement technique selected from the group consisting of multipass cavity-enhanced
absorption spectrometry (CEAS) and cavity ring-down spectroscopy (CRDS).
[0019] Another embodiment of the method is a method for freeze drying a
product. In that method, heat is removed from the product to freeze a solvent contained
in the product. The frozen solvent in the product is sublimed to form a solvent vapor
contained in a low-pressure gaseous effluent flowing away from the product. At least
some of the solvent vapor is condensed from the low-pressure gaseous effluent, and the
gaseous effluent is compressed using a vacuum pump. A concentration of at least one
trace material is measured in the gaseous effluent on a high-pressure side of the vacuum
pump.
[0020] The heat may be removed from the product using hollow freeze drying
shelves containing a heat transfer fluid. The material measured in the gaseous effluent
may be heat transfer fluid leaking from the shelves. The heat transfer fluid may contain a
perfluorinated fluid, in which case the concentration of the perfluorinated fluid is
measured using a halogen leak detector.
[0021] The condensation of solvent vapor from the low-pressure gaseous effluent
may comprise passing the low-pressure gaseous effluent through a condensation chamber
containing cooled condensing surfaces. In that case, the material measured in the
gaseous effluent may be a medium for cooling the condensing surfaces.
[0022] The material measured in the gaseous effluent may be a residual cleaning
material used in cleaning a process chamber. The cleaning material may be hydrogen
peroxide (H202) or chlorine dioxide (C102).
[0023] Another embodiment of the invention is a freeze dryer system. The
system includes a freeze drying chamber for containing product during the freeze drying
process; a condensation chamber in communication with the freeze drying chamber and
comprising surfaces for condensing solvent vapor from exhaust gas received from the
freezer drying chamber; a vacuum pump having a low pressure inlet and a high pressure
outlet, the low pressure inlet of the vacuum pump being in communication with the
condensation chamber; and a testing apparatus connected for receiving exhaust gas from
the high pressure outlet of the vacuum pump, the testing apparatus being for measuring a
presence of a material contained in the exhaust gas.
[0024] The freeze drying chamber may include hollow freeze drying shelves
containing a heat transfer fluid. In that case, the testing apparatus may measure trace
amounts of heat transfer fluid from the shelves. The heat transfer fluid may contain a
perfluorinated fluid, in which case the testing apparatus may be a halogen leak detector.
[0025] The surfaces for condensing solvent vapor in the condensation chamber
may comprise cooled condensing surfaces. In that case, the testing apparatus may
measure trace amounts of a medium for cooling the condensing surfaces that is leaking
into the condensation chamber.
[0026] The testing apparatus may measure trace amounts of a residual cleaning
material used to clean the process chamber. The cleaning material may be hydrogen
peroxide (H202) or chlorine dioxide (C102).
[0027] The testing apparatus may be an acousto-optic spectrometer. The testing
apparatus may be a multipass cavity-enhanced absorption spectrometer (CEAS) or cavity
ring-down spectrometer (CRDS).
[0028] Yet another embodiment of the invention is a method for freeze drying a
product. Heat is removed from the product in a freeze drying chamber to freeze a solvent
contained in the product. The frozen solvent in the product is sublimed to form a solvent
vapor contained in a low-pressure gaseous effluent flowing away from the product. The
gaseous effluent is compressed using a vacuum pump. The process is monitored by
measuring a concentration of solvent vapor in the gaseous effluent on the high-pressure
side of the vacuum pump.
Brief Description of the Drawings
[0029] FIG. 1 is a schematic drawing of a freeze drying system according to one
embodiment of the disclosure.
[0030] FIG. 2 is a schematic drawing of a prior art acousto-optic detection
system.
[0031] FIG. 3 is a flow chart showing a method in accordance with one aspect of
the disclosure.
[0032] FIG. 4 is a flow chart showing a method in accordance with another aspect
of the disclosure.
Description
[0033] The present disclosure describes systems and methods for performing an
emissions analysis on a specially conditioned gas stream. More specifically, the systems
and methods of the present disclosure monitor a freeze drying process for malfunctions,
and audit certain parameters of the process. To monitor conditions within the evacuated
process chambers, compressed gases at the exhaust side of the vacuum pump are
analyzed using gas analysis equipment 190 (FIG. 1) to determine the presence and
concentration of trace amounts of certain non-condensable gases. That information is
used to detect the presence and severity of leaks, and to measure process parameters.
[0034] Modern trace gas analysis equipment is capable of detecting
concentrations even at the parts-per-billion (ppb) level. The resolution of those systems
allows excellent discrimination between background gases and the gases to be
determined. This disclosure presents a technique whereby such trace gas analysis
equipment is placed on the high-pressure side of a vacuum pump in a freeze drying
process. That technique makes possible several diagnostic tools for monitoring a freeze
drying process, including the detection of small leaks of refrigerant and heat transfer
fluids, the detection of vacuum leaks from atmosphere, the detection of residual cleaning
materials, and the measurement of water vapor level during a secondary drying process.
The discriminatory characteristics of the gas analysis equipment are critical for placing
the equipment on the exhaust side of the vacuum pump, where oil from the pump, as well
as other impurities, may otherwise overwhelm the trace gases to be detected.
[0035] One example of such trace gas analysis equipment is the acousto-optic
spectrometer 200, shown schematically in FIG. 2. Acousto-optic spectrometry is a
technology used in determining extremely low concentrations of gases. The technology
is based on the generation of acoustic waves by the absorption of light energy. A gas
mixture 290 from the vacuum pump high pressure outlet 152 (FIG. 1) and containing a
target material is sampled through an inlet 210 into a chamber 220. In the chamber, an
optical laser 230 in the mid-IR region is gated to impinge on the material in the chamber.
When absorption takes place the gated absorption generates pressure waves 250 that can
be picked up by an acoustic microphone 260. By tuning the laser to the correct
absorption frequencies of the gas to be detected, the absorption level can be measured in
a direct way. The sensitivity of acousto-optic spectrometry is at the ppb level. The
measurements may be taken at atmospheric pressure or, in the case where a vacuum
booster pump (not shown) is used downstream of the vacuum pump outlet, may be taken
at sub-atmospheric pressure. Acousto-optic spectrometry is currently used in agricultural
applications to measure ethylene that is a phytohormone interfering with ripening fruit.
[0036] The inventors have discovered that gas analysis conducted on the highpressure
side of a vacuum pump may be used to monitor a freeze drying or similar
process. The technique 300, shown in the flow chart of FIG. 3, is actually an emissions
analysis of a specially conditioned gas stream for diagnostic purposes. The gas stream is
conditioned by first removing water vapor from the gas stream at 310. In a freeze drying
system, that step is performed by the condenser chamber, which condenses water from
the gas stream as ice. The remaining non-condensable gas is compressed at 320.
Compression in a freeze drying system is performed by a vacuum pump that compresses
gases from the condensing chamber. The conditioned and compressed gas stream is then
analyzed at 330 by a specific method.
[0037] An exemplary embodiment 400 of the method, as applied to a freeze
drying process, is illustrated by the flow chart of FIG. 4. Heat is removed from a product
at 410 to freeze water contained in the product. The heat removal process is conducted in
the freeze drying chamber, by forcing a heat transfer fluid through shelves that support
the product. By subjecting the frozen product to vacuum conditions and a slight
temperature increase, the frozen water in the product is sublimed at 420, forming water
vapor. The water vapor is contained in a low pressure gaseous effluent that flows away
from the product and out of the freeze drying chamber.
[0038] In a condensation chamber, the water vapor in the gaseous effluent is
condensed at 430 as ice that accumulates on condensing surfaces. The condensing
surfaces are cooled by a coolant that removes heat liberated by the condensation process.
In one exemplary embodiment, the surfaces are cooled to temperatures of -70°C to -90°C.
[0039] The non-condensable gases contained in the condensation chamber enter a
low-pressure intake of a vacuum pump, where the non-condensable gases are compressed
at 440. At the high-pressure exhaust of the vacuum pump, a concentration of trace
materials in those compressed gases is measured at 450.
[0040] The analysis of gas exhaust from the vacuum pump may be conducted
using acousto-optic spectrometry, as described above, or by any other technique capable
of detecting trace amounts of material in an atmospheric gas. For example, multipass
cavity-enhanced absorption spectrometry (CEAS) and cavity ring-down spectrometry
(CRDS) may be used. In each case, the vacuum pump serves as a barrier between the
measurement gauge and the sterile chambers, avoiding contamination of the chambers in
keeping with the requirements of the pharmaceutical industry.
[0041] In one exemplary embodiment, the system monitors flow from the vacuum
pump for the presence of heat transfer fluid that is contained within the shelves under
normal circumstances. Presence of even trace amounts of that fluid in the vacuum pump
exhaust may indicate leakage from the shelves into the freeze drying chamber.
[0042] The silicone oils used as heat transfer fluid in the shelves, as well as the
refrigerant oils used in the condenser coils, have very distinct spectra which differ from
the spectra of oils used in the common vacuum pumps. Where a spectrographic
technique such as acousto-optic spectrometry, multipass cavity-enhanced absorption
spectrometry (CEAS) or cavity ring-down spectrometry (CRDS) is used at the vacuum
pump exhaust, a calibration on the height of the most important absorption peaks of the
silicone heat transfer oils and/or refrigerant oils permits discrimination of those oils from
each other, from oils used in the vacuum pump, and from any other materials that may be
present in the vacuum pump exhaust.
[0043] The heat transfer oil may be a perfluorinated fluid that is easily detected
via a halogen leak detector. One such halogen leak detector suitable for use in the
presently described system is the D-TEK™ Select Refrigerant Leak Detector sold by
Inficon of Syracuse, NY, USA. That device detects the absorption of infrared energy by
a sample. The halogen leak detector is placed at the vacuum pump exhaust, as described
above. The perfluorinated fluid is used either entirely as the heat transfer fluid, or is
mixed with silicone oils in a quantity sufficient to be detected by the halogen leak
detector.
[0044] The presently described system may also be used to detect coolant leakage
from the condensation surfaces and coils in the condensation chamber. The coolant may
be detectable using a halogen leak detector, as described above, or may be a material
having distinct spectra that are monitored by other gas analysis equipment. As with the
product shelf heat transfer fluid, the condenser coolant may be perfluorinated to facilitate
detection in the vacuum pump exhaust.
[0045] A vacuum leak anywhere in the system may result in non-condensable
contaminants in the vacuum pump exhaust. While difficult to detect in low concentration
in the freeze drying and condensation chambers, those contaminants are compressed and
concentrated by the vacuum pump and may be detected using the techniques of the
present disclosure. For example, the gas analysis equipment may be configured to detect
spectra of common organic and inorganic contaminants that may be in the ambient
atmosphere. Those contaminants may occur naturally or may be introduced in the
ambient atmosphere for purposes of detection by the system. Alternatively, the gas
analysis equipment may be configured to detect any peak in the resulting spectrum that is
not present during ordinary operation of the equipment. In that case, a signature or
baseline spectrum may be established during a known problem-free run of the equipment.
A later measured spectrum containing new peaks would be considered suspect.
[0046] Yet another application of the presently described system is the detection
of trace gases remaining from materials that are used for other functions in the freeze
dryer. For example, vaporized hydrogen peroxide (H20 2) or chlorine dioxide (C102) is
used as a sanitizing agent in freeze drying systems between cycles. Like the silicone oils
discussed above, H20 2 has a very distinct spectrum in the mid-IR range. Measurements
made by the gas analysis equipment may therefore be used to determine if the
concentration of H20 2 is low enough to be acceptable for the initiation of production after
a sterilization cycle.
[0047] With the advent of a new, more efficient generation of dry vacuum pumps,
it may be possible to remove some amount of water from a product directly through the
vacuum pump, without the use of a condensation chamber. For example, a secondary
drying operation may be performed after most water is removed from the product using
the condensation chamber. In one example, a bypass conduit 130 (FIG. 1) is used to
bypass the condensation chamber 120, instead conducting gasses directly from the drying
chamber 110 to the vacuum pump 150. The small amount of remaining moisture in the
product 112 is sublimed and conducted directly through the vacuum pump 150. During
that step, the condensation chamber 120 may be regenerated (i.e., ice removed) for the
next cycle of primary drying .
[0048] During secondary drying, the rate of water vapor transport is very low.
Currently-used measurement techniques placed in the vacuum portion of the freeze
drying apparatus, such as tunable diode laser absorption spectroscopy (TDLAS), are
complicated by the low concentrations. By placing the gas analysis equipment on the
exhaust side of the dry vacuum pump, the concentration of water vapor can be deduced
and that information may serve as an indicator of the average remaining moisture level in
the product vials.
[0049] The above-described system, wherein the gas analysis is done on the
atmospheric pressure side of the vacuum pump, has many advantages over currently-used
systems. The reduced pressure gases are compressed on the exhaust side of the pump to
atmospheric pressure. While concentrations of those gases may still be low at
atmospheric pressure, there are more molecules that contribute to a specific signal
leading to detectable levels, permitting a wider choice of chemical analysis techniques.
In particular, optical spectroscopy technologies may be used.
[0050] Furthermore, where the analysis is done while the freeze drying process is
in progress, such as in shelf leak detection, the exhaust gas to be analyzed has been
stripped from the abundance of water vapor that would otherwise have swamped the
signal. The water vapor is frozen out on condenser coils at low pressure before the gas
stream reaches the vacuum pump. The vacuum pump compresses only the noncondensable
gases, which reveal the condition of the freeze dryer during the drying
process.
[0051] Because the gas analysis equipment is located outside the sterile zone of a
freeze drying system, current freeze dryer applications may be retrofitted with the
presently described system without the need for revalidation of the freeze drying process.
Installations for use in industries such as the pharmaceutical industry are therefore faster
and less costly.
[0052] The foregoing Detailed Description is to be understood as being in every
respect illustrative and exemplary, but not restrictive, and the scope of the invention
disclosed herein is not to be determined from the Description of the Invention, but rather
from the Claims as interpreted according to the full breadth permitted by the patent laws.
It is to be understood that the embodiments shown and described herein are only
illustrative of the principles of the present invention and that various modifications may
be implemented by those skilled in the art without departing from the scope and spirit of
the invention.
What is claimed is:
1. A method for analyzing a gas stream containing a solvent vapor,
comprising the steps of:
removing the solvent vapor from the gas stream to produce a noncondensable
gas stream;
compressing the non-condensable gas stream to produce a compressed gas
stream; and
measuring a concentration of a material in the compressed gas stream.
2 . The method of claim 1, wherein the gas stream containing solvent
vapor is an exhaust from a freeze drying chamber.
3. The method of claim 2 , wherein me freeze drying chamber includes
hollow freeze drying shelves containing a heat transfer fluid, and the material measured
in the compressed gas stream is heat transfer fluid leaking from the shelves.
4. The method of claim 3, wherein the heat transfer fluid contains a
perfluorinated fluid, and the step of measuring a concentration of a material comprises
measuring a concentration of the perfluorinated fluid using a halogen leak detector.
5. The method of claim 1, wherein the step of removing the solvent vapor
from the gas stream comprises passing the gas stream through a condensation chamber
containing cooled condensing surfaces.
6. The method of claim 5, wherein the measured material is a medium for
cooling the condensing surfaces that is leaking into the condensation chamber.
7. The method of claim 1, further comprising the step of:
cleaning a process chamber used in the method with a cleaning material,
and
wherein the measured material is residual cleaning material.
8. The method of claim 7, wherein the measured material comprises a
material selected from the group consisting of hydrogen peroxide (H20 2) and chlorine
dioxide (C102).
9 . The method of claim 1, wherein the step of measuring a concentration
of a material in the compressed gas stream further comprises using acousto-optic
spectrometry to measure the concentration of the material.
10. The method of claim 1, wherein the step of measuring a concentration
of a material in the compressed gas stream further comprises using a measurement
technique selected from the group consisting of multipass cavity-enhanced absorption
spectrometry (CEAS) and cavity ring-down spectroscopy (CRDS).
11. A method for freeze drying a product, the method comprising the steps
of:
removing heat from the product to freeze a solvent contained in the
product;
causing sublimation of the frozen solvent in the product to form a solvent
vapor contained in a low-pressure gaseous effluent flowing away from the product;
condensing at least some of the solvent vapor from the low-pressure
gaseous effluent;
compressing the gaseous effluent using a vacuum pump; and
measuring a concentration of at least one trace material in the gaseous
effluent on a high-pressure side of the vacuum pump.
12. The method of claim 11, wherein the heat is removed from the product
using hollow freeze drying shelves containing a heat transfer fluid.
13. The method of claim 12, wherein the material measured in the gaseous
effluent is heat transfer fluid leaking from the shelves.
14. The method of claim 13, wherein the heat transfer fluid contains a
perfluorinated fluid, and the step of measuring a concentration of at least one trace
material comprises measuring a concentration of the perfluorinated fluid using a halogen
leak detector.
15. The method of claim 11, wherein the step of condensing at least some
of the solvent vapor from the low-pressure gaseous effluent comprises passing the lowpressure
gaseous effluent through a condensation chamber containing cooled condensing
surfaces.
16. The method of claim 1 , wherein the material measured in the gaseous
effluent is a medium for cooling the condensing surfaces.
17 . The method of claim 11, further comprising the step of:
cleaning a process chamber used in the method with a cleaning material,
and
wherein the material measured in the gaseous effluent is residual cleaning
material.
18 . The method of claim 17 , wherein the material measured in the gaseous
effluent comprises a material selected from the group consisting of hydrogen peroxide
(H20 2) and chlorine dioxide (C102) .
19. The method of claim 11, wherein the step of measuring a
concentration of at least one trace material in the gaseous effluent on a high-pressure side
of the vacuum pump further comprises using acousto-optic spectrometry to measure the
concentration of the material.
20. The method of claim 11, wherein the step of measuring a
concentration of at least one trace material in the gaseous effluent on the high-pressure
side of the vacuum pump further comprises using a measurement technique selected from
the group consisting of multipass cavity-enhanced absorption spectroscopy (CEAS) and
cavity ring-down spectroscopy (CRDS).
2 1. A freeze dryer system, comprising:
a freeze drying chamber for containing product during the freeze drying
process;
a condensation chamber in communication with the freeze drying chamber
and comprising surfaces for condensing a solvent vapor from exhaust gas received from
the freezer drying chamber;
a vacuum pump having a low pressure inlet and a high pressure outlet, the
low pressure end of the vacuum pump being in communication with the condensation
chamber; and
a testing apparatus connected for receiving exhaust gas from the high
pressure outlet of the vacuum pump, the testing apparatus being for measuring a presence
of a material contained in the exhaust gas.
22. The system of claim 21, wherein the freeze drying chamber comprises
hollow freeze drying shelves containing a heat transfer fluid.
23. The system of claim 22, wherein the testing apparatus measures trace
amounts of heat transfer fluid from the shelves.
24. The system of claim 23, wherein the heat transfer fluid contains a
perfluorinated fluid, and the testing apparatus is a halogen leak detector.
25. The system of claim 21, wherein the surfaces for condensing solvent
vapor in the condensation chamber comprise cooled condensing surfaces.
26. The system of claim 25, wherein the testing apparatus measures trace
amounts of a medium for cooling the condensing surfaces that is leaking into the
condensation chamber.
27. The system of claim 21, wherein the testing apparatus measures trace
amounts of a residual cleaning material used to clean the process chamber.
28. The system of claim 27, wherein the cleaning material comprises a
material selected from the group consisting of hydrogen peroxide (H20 2) and chlorine
dioxide (C102) .
29. The system of claim 21, wherein the testing apparatus is an acoustooptic
spectrometer.
30. The system of claim 21, wherein the testing apparatus is an apparatus
selected from the group consisting of a multipass cavity-enhanced absorption
spectrometer (CEAS) and cavity ring-down spectrometer (CRDS).
31. A method for freeze drying a product, the method comprising the steps
of:
removing heat from the product in a freeze drying chamber to freeze a
solvent contained in the product;
causing sublimation of the frozen solvent in the product to form a solvent
vapor contained in a low-pressure gaseous effluent flowing away from the product;
compressing the gaseous effluent using a vacuum pump;
monitoring the freeze drying by measuring a concentration of the solvent
vapor in the gaseous effluent on the high-pressure side of the vacuum pump.