Surgery – Means for introducing or removing material from body for... – Treating material introduced into or removed from body...
Reexamination Certificate
2000-05-31
2002-08-27
Walberg, Teresa (Department: 3742)
Surgery
Means for introducing or removing material from body for...
Treating material introduced into or removed from body...
C604S082000, C604S087000, C604S122000
Reexamination Certificate
active
06440101
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to syringe systems that are suitable for packaging, mixing and delivering a medical solution formed by mixing a dry, lyophilized drug component with a liquid diluent. More specifically, the invention relates to syringe systems that permit lyophilization of a drug solution contained therein. The invention also relates to methods of making such syringe systems.
BACKGROUND OF THE INVENTION AND TECHNICAL PROBLEMS POSED BY THE PRIOR ART
Generally, lyophilization is a process by which the volatile components, such as solvents including water, are removed from a substance. Certain substances, especially pharmaceutical substances, are more stable over time if the volatile components are removed. Since lyophilized drugs are typically more stable, have longer shelf life, have more reliable purity and are easier to store and transport than other formulations, lyophilization has become commonplace in the pharmaceutical industry.
It is known to provide “wet/dry” drug mixing and delivery products that utilize a primary syringe system, containing a lyophilized drug, and a secondary syringe system that contains a diluent used to reconstitute the lyophilized drug. When the drug is to be administered to a patient, the secondary syringe system is inserted into the primary syringe system and the diluent is dispensed into the primary syringe barrel to reconstitute the lyophilized drug. These “wet/dry” syringe systems are useful in pharmaceutical applications where pre-mixed solutions or suspensions of a drug are not stable enough to withstand prolonged periods of storage. Such systems are disclosed in U.S. Pat. No. 5,779,668, the subject matter and entire writing of which is incorporated herein by reference.
Typically, the manufacture of the primary syringe system containing the lyophilized drug involves mass processing of a number of syringe systems in a lyophilization chamber. Prior art lyophilization chambers are exemplified by FIG.
1
and U.S. Pat. No. 4,506,455, the subject matter and entire writing of which is incorporated herein by reference. The lyophilization chamber
10
generally comprises a chamber wall
12
which is manufactured to provide insulation during the lyophilization process. Enclosed within the wall
12
are a series of shelves
14
which are adapted to move relative to one another and which include implements, such as refrigeration and heating coils, for raising and lowering the temperature of the shelves. A hydraulic actuator
18
moves the top shelf upward, creating a space between the top shelf and the adjacent second shelf, and a number of syringe systems
22
, supported on trays or “pucks”
20
are loaded onto the second shelf. The containers or trays
20
are typically transported on a transport carriage
26
and slid across a loading table
24
such that the trays can be loaded onto the respective shelves
14
. The top shelf and second shelf are then raised and syringe systems
22
are loaded onto the third shelf. This loading sequence is repeated until the upright syringe systems
22
occupy the spaces between the shelves
14
. Once fully loaded, the chamber door
19
is closed and the interior subjected to a lyophilization process which may typically take a number of days to complete. After the lyophilization process is complete, the top shelf is lowered and the shelves are collapsed towards one another such that movement of the shelves causes a collapse and therefore sealing of the syringe systems
22
in a manner that will be described below.
Typical lyophilization processes involve two stages. In the first stage, the drug solution is subjected to low temperatures, typically −50 (C) and completely frozen to separate the water or other solvent from the solute ingredients. In the second stage, the water or other solvent is separated from the frozen product by heating the contents slowly, under carefully controlled conditions, and under high vacuum so that the solvent leaves the products through sublimation. Drying is accomplished as the frozen solvent is transformed into vapor. This vapor migrates through the crystallized drug and escapes from the syringe system through a venting system.
FIGS. 2 and 3
illustrate a prior art syringe system for permitting venting of the drug during lyophilization. During the lyophilization process, the syringe system
30
is maintained in an upright position in a metal holder or puck (not shown).
FIG. 2
illustrates the syringe system
30
configured in a venting position. The syringe system
30
comprises a generally cylindrical syringe barrel
32
which includes an open end
33
and a closed end
34
. The closed end
34
includes a delivery passage
36
which is later used for delivery of the mixed drug from the syringe system
30
. During lyophilization, the delivery passage
36
is sealed by a closure
37
and the syringe barrel
32
contains a drug solution
35
.
In accordance with prior art syringe systems, venting is provided by a series of venting channels
39
which are formed in the syringe barrel
32
near the open end
33
. These channels are formed between a series of ribs
37
that are integrally molded with the syringe barrel
32
. The syringe system
30
also includes a sterility maintenance sleeve
42
and plug cap
56
which are intended to seal the interior of the syringe barrel
32
against contamination once the syringe is moved into its sealed position as shown in FIG.
3
. The sterility maintenance sleeve
42
includes a large diameter portion
52
from which extends a stopper retaining head
50
that is shaped to resiliently retain a rubber stopper
44
thereon. Stopper
44
is adapted to sealingly engage the interior surface of the syringe
32
and, in the venting position as shown in
FIG. 2
, abuts the ribs
37
thereby permitting egress of vapor through the channels
39
from the drug chamber
45
of the syringe
32
.
FIG. 3
illustrates the syringe system
30
configured in a sealing position after the lyophilization process has been performed. The sterility maintenance sleeve
42
and plug cap
56
are moved to the sealing position in which the stopper
44
is located further into the syringe
32
and a sealing head
57
of the plug cap
56
engages the syringe
32
. As will be recognized by those of ordinary skill in the art, the plug cap and sterility maintenance sleeve
42
are moved to the sealing position from the venting position by movement of the shelves in the lyophilization chamber.
Prior art syringe systems require a rather extensive vertical travel of the sealing components when moving from a venting position to a sealing position. This travel dimension places limits on the capacity of the lyophilization chamber since the shelves must be spaced to accommodate the syringe system when it is configured in the venting position. Since lyophilization processes may take several days for some pharmaceutical substances, space within the lyophilization chamber—typically a very expensive piece of equipment—is at a premium. It would therefore be desirable to provide a syringe system which requires less vertical movement for sealing compared to prior art syringe systems. Such a system would permit more efficient use of the space within the lyophilization chamber.
The venting techniques of prior art syringe systems are also disadvantageous in that they do not provide an efficient flow path for drug solution vapor during the drying steps of lyophilization. More specifically, the fluid path that vapor must travel to escape from the drug chamber to the ambient surroundings during lyophilization is somewhat restricted, since the venting passages are formed by the engagement of a resilient stopper with channels formed in the syringe barrel. It would therefore be desirable to provide a syringe system which provides an efficient flow path for drug solution vapors during lyophilization, thereby decreasing the time required for drying during lyophilization.
SUMMARY OF THE INVENTION
The benefits and advantages described above are realized by the present inve
Farmer Randall M.
Grabenkort Richard W.
Abbott Laboratories
Dahbour Fadi H.
Vrioni Beth A.
Walberg Teresa
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