Plastic and nonmetallic article shaping or treating: processes – Mechanical shaping or molding to form or reform shaped article – To produce composite – plural part or multilayered article
Reexamination Certificate
1999-08-11
2001-11-27
Ortiz, Angela (Department: 1732)
Plastic and nonmetallic article shaping or treating: processes
Mechanical shaping or molding to form or reform shaped article
To produce composite, plural part or multilayered article
C264S268000, C264S250000
Reexamination Certificate
active
06322739
ABSTRACT:
FIELD OF INVENTION
The invention relates to a process of preparing pharmaceutical closures for containers made of flexible polymeric materials which are suitable to be filled with parenterally administerable fluids prior to their sealing and sterilization. More particularly, closures are prepared which have an excellent resealing capacity after being penetrated by a piercing device for establishing fluid communication with the container, even after multiple entries into the container.
BACKGROUND OF THE INVENTION
The efforts of providing containers of polymeric materials for parenterally administerable products which are sterilizable after being finally filled and assembled, but also safe from migration of potentially hazardous agents and easy to recycle, have been previously disclosed in the International patent applications WO 95/08317, WO 97/37628 and WO 97/39952.
EP 0 097 054 (Hantakki Oy) discloses a flexible bag for medical fluids provided with an injection port which has a closure comprising a shielded resilient pierceable pad which reseals after penetration and which also may be protected from the stored fluids. This type of closure has the drawback in that it is quite complicated to assemble from different parts in the moment of sealing the ports and therefore is less suitable in an aseptic environment.
U.S. Pat. No. 4,303,067 (American Hospital Supply Corp.) describes an additive port for a medical bag through which medicals can be supplied by an injection device. The port has a puncturable, reasealable plug made of an elastomer. Nothing is disclosed about the resealing capacity or the sterilizability of the closure.
U.S. Pat. Nos. 4,975,308 and 5,247,015 describe molded stoppers for blood tubes made of a halobutyl rubber dispersed in a mixture of polyolefins and a thermoplastic elastomer. No disclosures are given herein about their resealing capacity after needle penetration or their capacity of being heat sterilized.
There are numerous other citations in the literature of closures for pharmaceutical containers of various types, both made of glass or of polymeric materials which are disclosed to be suitable to seal stored fluids for parenteral administration. Generally, it is a requirement from medical authorities that such closures must be capable of maintaining a barrier against the environment, both during sterilization by steam and during subsequent long term storage. It is also required that this type of closures shall be capable to reseal spontaneously and immediately after the withdrawal of a penetrating needle. They must also have a resealing capacity after multiple entries by penetrating needle, a cannula or a similar penetrating device suitable for collecting fluid from the container or for adding a component to be mixed with the contents of the container. An improper resealing of the closure after penetration potentially will waste the integrity of stored fluids by providing a channel for microbial growth into the container. It is also a requirement that the container must not leak when its closure is penetrated during fluid connection, for instance during infusion to a patient through a cannula. Furthermore, the closure must be compatible with stored fluids and no migration of potentially hazardous agents from any of its parts is allowed. The closure must also withstand conventional sterilization processes including autoclavation at 121° C. and sterilization by irradiation without losing any of its sealing capacity. It is also a requirement set by an increasing amount of medical authorities that each authorized container must be possible to recirculate and its therefore a demand that empty containers shall be possible to dispose without laborious disassembling and sorting of parts for individual recycling processes.
In the aforementioned International patent application WO 97/39952, ports for containers storing parenterally administerable fluids having closures generally fulfilling several of these requirements are disclosed which are designed to have all important parts correctly sterilized by pressurized steam in the autoclave. These closures typically comprise a frame or carrier part for a penetrable plug, wherein said carrier is adapted to seal an orifice by weak seal weldings or by being clamped in the orifice of the container. The penetrable plug of the closure is intended to be pierced by a device for establishing fluid communication with the container e.g. an injection syringe. As described in the previously mentioned Swedish patent application SE 9601540-9, such a closure can be produced in a two-color mold process wherein the generally sleeve formed carrier first is molded of thermoplastic material in a desired shape to sealingly fit with a container orifice, whereupon liquefied thermoplastic elastomer is injected into the sleeve to form the penetrable plug. These closures are highly advantageous over prior art sealing means by their simple production process and their comparatively simple assembly in a sealing position in a container orifice without extra time consuming steps, where their various parts must be assembled to form an adequate sealing device.
It is, however, a considerable technical problem to repeatedly manufacture this type of closures under conditions such that the elastomer plug obtains suitable characteristics of being resealable after multiple entries into the container by piercing devices, while it at also at the same time must form sealing adhesive bondings along the contact surface with the inner periphery of the carrier, so the two-part closure perfectly may seal against the environment. In particular, it has been connected with problems to find a reliable process which is reproducible in giving the penetrable plug specific resealing characteristics in a conventional two-part molding technique. This type of closure must also preferably be capable of forming a reliable seal with the container orifice, for example by forming weak seal weldings, as described in the above mentioned International patent application WO 95/08317.
DESCRIPTION OF INVENTION
It is an object of the present invention to provide a process for manufacturing pharmaceutical closures with a pierceable plug of an elastomeric material which safely reseals itself after being pierced with a syringe, a cannula or similar device capable of adding or withdrawing a fluid from a medical container.
It is also an object of the invention to provide a process which is highly reproducible in giving the pierceable plugs a resealing capacity after being pierced at least according to the DIN 58 363 part 15 standard.
It is a further object of invention to provide such a method of preparing pierceable plugs in a two-part injection molding technique to form adhesive bondings of an elastomer part and a carrier part in a highly reliable manner without employing any bonding agents and with low risk of contamination, while at the side time avoiding the formation of cavities between the two parts.
Another object of the present invention is the provision of pharmaceutical closures which consists polyolefins to such an extent that both the closure and the polyolefinic container body can be recirculated together without being disassembled and separately collected, while having a resealing capacity at least according to the DIN 58 363 part 15 standard.
A further object of the present invention is to provide pharmaceutical closures with the mentioned resealing capacity which are possible sterilize by high pressure steam (autoclavation) or by irradiation in a single process after being assembled with the container and maintain its integrity and other important characteristics, while being compatible with substantially all infusion fluids including lipophilic fluids like lipid emulsions without causing migration of potentially toxic agents.
A still further object of the present invention is to provide pharmaceutical closures of a two-part comprising a pierceable plug of an elastomer in a carrier part wherein said carrier part is provided with means for deleting cavities formed during th
Andersson Gunnar
Mulligan Des
Fresemus Kabi AB
Ortiz Angela
Pepper Hamilton LLP
Pouliquen Corinne M.
Villacorta Gilberto M.
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