Metal working – Method of mechanical manufacture – Assembling or joining
Reexamination Certificate
1995-08-22
2001-02-20
Rosenbaum, I Cuda (Department: 3726)
Metal working
Method of mechanical manufacture
Assembling or joining
C029S422000, C053S428000
Reexamination Certificate
active
06189195
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
This invention relates in general to manufacturing processes for syringes, and more particularly to manufacturing processes for syringes prefilled with a fluid, such as a diagnostic contrast media or drug, where at least one of the syringe components is manufactured in at least a class 100 environment.
BACKGROUND OF THE INVENTION
Prefilled syringes provide convenience of use by eliminating the need to load the syringe with a fluid, such as contrast media, and by minimizing the need to purge air. Manufacturing processes for prefilled syringes are known in the art. For example, processes are known for producing prefilled, sterile glass syringes whereby the manufactured syringe components are washed and sterilized prior to partial assembly. The partially assembled glass syringe is filled with a fluid, sealed with a plunger, and sterilized once again by heating. U.S. Pat. Nos. 4,718,463 and 4,628,969, both issued to Jurgens, Jr. et al., teach a process for manufacturing plastic, prefilled syringes using repeated water jet washing of the syringe components prior to assembly and filling. Water washing is expensive because it requires ultra-purified water. Water washing is also troublesome because it is difficult to inspect and insure satisfactory cleaning. Therefore, it is desirable to reduce the number of washing steps required in the manufacture of prefilled syringes. Further, prior art syringe manufacturing processes do not provide precautionary steps to maintain syringe components substantially free from contaminants, such as viable and nonviable particles, during molding, assembly and filling. Therefore, it is desirable to develop a method for manufacturing prefilled syringes which substantially reduces viable and nonviable particles that may contaminate the syringe components during molding, assembly and filling.
SUMMARY OF THE INVENTION
This invention relates to a process for manufacturing prefilled syringes which reduces the number of component washing steps and permits the molding, assembly and filling of components substantially free of contaminants. A typical syringe which can be manufactured by the process of the invention includes a barrel, plunger substrate, plunger cover and tip seal.
In general the process begins by molding the barrel and plunger substrate from non-elastomeric material, such as polypropylene, polycarbonate or other medical grade plastic, within at least a class 100 environment. A class 100 environment, as used herein, is defined as an environment having no more than 100 viable or nonviable particles per cubic foot of air, 0.5 microns and larger. Further, this manufacturing environment should be at least a MCB-3 environment. A MCB-3 environment, as used herein, is defined as an environment wherein the microbial level of gram positive microorganisms is less than 3 cfu (colony forming unit) per cubic foot of air, and the microbial level of gram negative microorganisms is less than 1 cfu per cubic foot of air.
The molding temperature for the barrel and plunger substrate may be selected such that it renders these components substantially sterile and substantially free from contaminants. Any contaminants, such as particulate matter, that may exist in the air within the class 100 environment proximate to the components after molding may be removed from the class 100 environment by air flow. Thus, the barrel and plunger substrate manufactured under these conditions need not be washed.
The plunger cover and tip seal are molded from an elastomeric material, such as rubber, by any suitable molding method such as compression molding. As it is typically more difficult to compression mold these components within a class 100 environment due to the procedures and materials used, these components are manufactured in an environment less clean than a class 100 environment. Specifically, compression molded components are typically formed from a large sheet of rubber material. After the rubber has vulcanized in the mold, the entire sheet of molded components is removed from the mold and trimmed. The trimming process generates particulate matter from the cutoffs and lubrication that is used. Any contaminants that may exist on the plunger cover or tip seal after molding are removed by any suitable method, such as the use of ultrasonic or jet washing with freon or ultra-purified water, otherwise referred to as water-for-injection. The plunger cover and tip seal are then transferred to a class 100 environment.
After molding and contaminant removal, the plunger cover and tip seal are lubricated with silicone oil, hereinafter referred to as “silicone”, to facilitate the assembly of the plunger cover onto the plunger substrate to form the plunger, and the assembly of the tip seal to the distal end of the barrel to form the barrel/tip seal combination. The plunger cover and tip seal may also require sterilization by any suitable method, such as use of ethylene oxide or autoclaving. After assembly of the plunger and the barrel/tip seal combination within at least a class 100 and MCB-3 environment, the barrel/tip seal combination is filled with a fluid, such as a contrast medium or drug, and the plunger is inserted therein to complete the assembly of the prefilled syringe.
Oftentimes different manufacturing steps take place at different locations. In this instance, it is desirable to package the components or partially assembled components in packaging that will maintain the components or partially assembled components substantially free from contaminants while being transported from one manufacturing location to another. In a preferred embodiment of the invention, the components or partially assembled components within at least a class 100 environment are “triple-bagged” to prevent contamination. Specifically, the components or partially assembled components are inserted into separate first and second containers, such as plastic bags, which are sealed to prevent entry of contamination. The packaged components or partially assembled components are then transferred to an environment less clean than a class 100 environment, such as a class 10,000 environment, where they are placed in a third container, such as a plastic bag, which is sealed to prevent entry of contaminants. A class 10,000 environment, as used herein, is defined as an environment having no more than 10,000 viable or nonviable particles per cubic foot of air, 0.5 microns and larger. The third bag is then placed in a shipping box for delivery to the next manufacturing location.
Upon arrival at the next manufacturing location, the shipping box is placed in an environment less clean than a class 100 environment, such as a class 10,000 environment. The packaged components or partially assembled components are then removed from the box and third bag, and placed in a feedthrough box connected to at least a class 100 environment, where they are removed from the second bag. The second bag remains in the feedthrough box, and the first bag containing the packaged components or partially assembled components is transported to into the class 100 environment. The packaged components or partially assembled components are removed from the first bag and set up for further manufacturing steps. It is understood that the components and partially assembled components can be transferred to any number of manufacturing locations by using the packaging and unpackaging procedures of the present invention.
In the manufacturing process of the invention, a salient technical advantage is that the number of washing steps required by the prior art is substantially reduced and the syringe components are molded, assembled and filled substantially free from contaminants.
REFERENCES:
patent: 3105335 (1963-10-01), Hickey
patent: 3202084 (1965-08-01), Hale et al.
patent: 3634997 (1972-01-01), Tait
patent: 4267769 (1981-05-01), Davis et al.
patent: 4391080 (1983-07-01), Brody et al.
patent: 4628969 (1986-12-01), Jurgens, Jr.
patent: 4660464 (1987-04-01), Tanaka
patent: 4677980 (1987-07-01), Reilly
patent: 4718463 (1988-
Gelblum Eugene A.
Hitchins Mark W.
Reilly David M.
Rhinehart Edward J.
Robinson Michelle
Bradley Gregory L.
Cuda Rosenbaum I
Medrad Inc.
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