SOUTHARDS, Alan (3520 E. Nickell Terrace, St. Joseph, MO, 64506, US)
| I claim:
1 . A lyophilization chamber temperature monitoring device comprising a body formed of thermally conductive material and presenting at least one bore therein sized to receive a temperature monitoring unit, said body having a substantially flat bottom surface
5 adapted for close contact with a shelf surface of said lyophilization chamber.
2. The device of claim 1, said body formed of metal.
3. The device of claim 2, said body formed of brass. K)
4. The device of claim 1, including a pair of spaced apart bores each sized to receive a temperature monitoring unit therein.
5. The device of claim 4, said body presenting opposed upper and lower 15 faces, one of said bores being a through bore extending between said upper and lower faces, the other of said bores extending generally parallel and closely adjacent to said lower face.
6. The device of claim 1, said bore sized to receive a thermocouple.
20 7. A temperature monitoring assembly comprising a body formed of thermally conductive material and presenting at least one bore therein, said body having a substantially flat bottom surface adapted for close contact with a shelf surface of said lyophilization chamber, and a temperature monitoring unit operative Iy received within said bore.
25 8. The assembly of claim 7, said body formed of metal.
9. The assembly of claim 8, said body formed of brass.
10. The assembly of claim 7,said body including a pair of spaced apart bores, 30 said unit being alternatively receivable within each bore respectively.
11. The assembly of claim 10, said body presenting opposed upper and lower faces, one of said bores being a through bore extending between said upper and lower faces, the other of said bores extending generally parallel and closely adjacent to said lower face.
12. The assembly of claim 7, said unit being a thermocouple.
13. A method of monitoring temperature conditions within a lyophilization chamber, comprising the steps of: providing a plurality of bodies each formed of thermally conductive material and presenting at least one bore therein sized to receive a temperature monitoring unit, said bodies having a substantially flat bottom surface adapted for close contact with shelf surfaces of said lyophilization chamber; installing a temperature monitoring unit in each of said body bores; locating said plurality of bodies at discrete, spaced apart locations on shelves within said lyophilization chamber; operating said lyophilization chamber; and collecting temperature data from at least certain of said plurality of temperature monitoring units during the course of said chamber operation.
14. The method of claim 13 , including the steps of placing respective bodies adjacent the inlet and outlet of certain of said shelves.
15. The method of claim 13, each of said bodies formed of metal.
16. The method of claim 15, each of said bodies formed of brass.
17. The method of claim 13, each of said bodies including a pair of spaced apart bores each sized to receive a temperature monitoring unit therein.
18. The method of claim 17, each of said bodies presenting opposed upper and lower faces, one of said bores of each body being a through bore extending between said upper and lower faces, the other of said bores of each body extending generally parallel and closely adjacent to said lower face.
19. The method of claim 13, including the step of installing a thermocouple in each of said bodies. |
METHOD AND APPARATUS FOR ACCURATE TEMPERATURE MONTTORTNG TN
LYOPHILIZATION CHAMBERS
BACKGROUND OF THE INVENTION Field of the Invention
The present invention is broadly concerned with improved devices for monitoring conditions within lyophilization chambers, in order to ensure that uniform temperature conditions are maintained throughout the course of lyophilization. More particularly, the invention is concerned with such devices, complete thermal measuring assemblies and methods of use thereof, wherein the devices are in the form of compact, thermally conductive bodies provided with strategically located bores for receipt of temperature measuring units such as thermocouples or the like.
Description of the Prior Art
Lyophilization equipment requires initial and periodic operation qualification (OQ) testing to determine how well the equipment performs critical functions during lyophilization cycles. The lyophilization process requires that temperatures be closely controlled from the time that product is loaded onto the lyophilizer shelves until it is removed in a processed condition. The OQ tests include monitoring the heat transfer required to freeze and then sublimate ice in the product. A comprehensive OQ study must therefore verify cooling and heating rates, control at the set point, and temperature uniformity throughout the lyophilization chamber.
For example, shelf temperature uniformity should be verified across all shelves of the lyophilization chamber, and any variations must be within an acceptable range to assure product batch uniformity. Temperature uniformity testing normally involves monitoring various locations across each shelf, such as at the center and four corners, or at the inlet and outlet areas of the shelves, with a comparison between the temperature at those locations and between all of the shelves. This is conventionally accomplished by a thermal mapping of the chamber using thermocouples placed in physical contact with the shelves. However, no convenient method is available for securing the thermocouples to the shelves. In some cases, thermocouples are
positioned using adhesives or adhesive tape, but this inevitably leaves an adhesive residue on the shelves which can be difficult to remove. It has also been known to use mechanical spring devices to hold the thermocouples in place. Such hold-downs are time consuming to set up and clean following testing. Whether tape or mechanical hold-downs are employed, generally only the front of the shelves can be verified, because the rear portions of the shelves are difficult to physically reach for placement of thermocouples.
There is accordingly a need in the art for improved devices which can be mated with thermocouples or other temperature monitoring units to create complete temperature monitoring assemblies, and wherein the assemblies can be conveniently placed at selected shelf locations within a lyophilization chamber. Tt is especially important that the assemblies be usable without the need for adhesives, tape or mechanical hold-down devices.
SUMMARY OF THE INVENTION
The present invention overcomes problems outlines above and provides significantly improved devices and assemblies for lyophilization chamber temperature monitoring. Broadly speaking, temperature monitoring devices of the invention comprise a body formed of thermally conductive material and presenting at least one bore therein sized to receive a temperature monitoring unit. The body has a substantially flat bottom surface adapted for close contact with a shelf surface of a lyophilization chamber, thereby assuring accurate temperature monitoring. Additionally, the body is of sufficient mass to resist inadvertent movement during temperature extremes of lyophilization cycles.
In preferred forms, the thermal conducting bodies are formed of a metal such as aluminum or brass, with the latter being preferred. Additionally, the bodies preferably include a pair of spaced apart bores each sized to receive a temperature monitoring device such as a thermocouple.
In use, a plurality of temperature monitoring assemblies made up of individual puck devices and associated temperature monitoring units are placed in spaced relationship on shelves within a lyophilization chamber, and the units are operatively coupled with data acquisition equipment. The chamber is then operated and temperature data is collected from at least certain of the monitoring units during the course of lyophilization.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a plan view of a thermal puck device in accordance with the invention; Fig. 2 is a vertical sectional view of the thermal puck device taken along line 2-2 of Fig. i; Fig.3 is a vertical sectional view of a monitoring assembly comprising a the thermal puck device with a thermocouple positioned in the device, during use on a shelf of a lyophilization chamber;
Fig. 4 is a perspective view of the assembly illustrated in Fig. 3;
Fig. 5 is a perspective view of a monitoring assembly made up of a thermal puck device with an installed thermocouple, using an alternate mounting bore for the thermocouple; and
Fig. 6 is a temperature vs. time chart illustrating the use of the monitoring assemblies of the invention during actual temperature measurements during lyophilization.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Turning now to the drawings, a thermal puck device 10 is illustrated which is designed to facilitate accurate temperature monitoring at various locations within a large commercial lyophilization chamber. The device 10 is in the form of a metallic body 12 having at least one thermocouple-receiving bore 14 therein. As best illustrated in Fig. 3, the device 10 is adapted to sit upon a shelf 16 of a lyophilization chamber to provide accurate temperature monitoring through a thermocouple 18 carried by the device.
In more detail, the body 12 is generally cylindrical in configuration, presenting upper face 20, an opposed 22, and a continuous sidewall 24. Preferably, the body has a diameter of from about 3/4-3 inches, and more preferably about 1 Vz inches. The body should have a height of from about 1/4-1 1 A inches, more preferably about 1 A inch. While the body 12 can be fabricated from any material possessing good thermal conductivity, in preferred practice, it is fabricated from brass, so that it will possess sufficient mass to resist movement which could potentially invalidate temperature monitoring results.
In the form shown, the body 12 is provided with a pair of bores 14a and 14b. The bore 14a is located closely adjacent and generally parallel with bottom surface 22, for example, from about 0.075-0.150 inches, more preferably about 0.125 inches, from the surface 22. On the other hand, upright bore 14b extends as a through bore between the top and bottom surfaces 20, 22. Body 12 is also provided with a pair of threaded bores 26a and 26b respectively located in
communication with a corresponding bore 14a or 14b. The bores 26a and 26b are threaded and are adapted to receive set screws 28a and 28b.
In the use of device 10, a standard thermocouple 18 may be located within either bore 14a or 14b, and the corresponding set screw 28a or 28b is used to lock the thermocouple in place. As depicted in Fig. 4, thermocouple 18 having tip 18a is located within upright bore 14b and extends throughout the entirety thereof so that tip 18a will make direct contact the upper surface of shelf 16. This configuration is used where there is adequate clearance between adjacent shelves of a lyophilization chamber. Where this spacing is not adequate, the thermocouple 18 is positioned within the bore 14a (see Fig. 5), thereby giving the overall monitoring assembly a low profile.
The device 10 with a thermocouple 18 mounted therein can be used to give very accurate temperature measurements at various locations within a lyophilization chamber. It is only necessary to install a thermocouple into each device 10 to be used, followed by placing of the resulted assemblies at selected shelf locations within a lyophilization chamber. The temperature recorded by the thermocouples can then be easily monitored and analyzed using conventional data acquisition hardware.
Fig. 6 illustrates the result of one study wherein 32 separate monitoring assemblies were employed during use of a standard pharmaceutical lyophilization chamber. Each puck was equipped with a conventional thermocouple located in the upright position depicted in Figs. 3 and 4, and the thermocouples were coupled with standard data logger equipment. An assembly was placed at the inlet and outlet of 16 shelves, in direct contact with the shelf surfaces. This was done in order to determine if the chamber was maintaining an essentially uniform temperature profile throughout. As illustrated in Fig. 6, the results demonstrate that most of the assemblies gave substantially similar temperature profile results, but that one shelf had substantially different temperature conditions during a portion of the lyophilization cycle. Thus, it was determined that the chamber needed adjustment in order to ensure proper temperature conditions throughout the entirety of the lyophilization process.
Other testing with the puck devices of the invention confirms that essentially equivalent results are obtained when thermocouples arc located in the horizontal position as illustrated in Fig. 5. In preferred practice however, the upright or vertical position is preferred inasmuch as the tips 18a of the thermocouples 18 are placed in direct contact with shelf surfaces in this orientation.