A significant portion of injectable sterile liquid medications presently distributed by pharmaceutical manufacturers is in the form of pre-filled injection syringes containing a sterile medicament which had been placed in a pre-sterizilized syringe-needle assembly unit.
The syringe barrel, which serves as the container for the medicament, is usually fabricated from glass in order to comply with compendial and regulatory requirements for purity and stability of the medicament preparation contained therein. Since the active medicament preparation can rarely withstand the sterilization techniques usually employed to sterilize the syringe-needle assembly because of possible degradation and/or inactivation of the active medicament, the syringe-needle assembly unit is separately sterilized prior to the introduction under aseptic conditions of a sterile medicament preparation into the barrel of the sterile syringe, and a plunger (closure) is inserted into the filled syringe barrel by the displacing the air by means of an air outlet tube.
In order to prevent the medicament preparation in the syringe barrel from leaking out through the attached needle, the needle, prior to the sterilization of the syringe-needle assembly unit is imbedded or inserted into a sleeve-closure unit, preferably made of rubber or rubber-like material. This sleeve-closure unit serves to prevent leakage and to cover the entire needle thereby maintaining the sterility of the entire needle. An example of such sleeve-closure unit is shown in U.S. Pat. No. 3,865,236.
In this system the sleeve-closure unit, which covers the entire needle up to the hub, also creates a dead space wherein the sterilizing means cannot readily penetrate. This is particularly true in respect of the tip portion of the needle which is imbedded or inserted into the sleeve-closure unit; since the portion of the needle which directly enters the tissue of the recipient may not be effectively sterilized.
This problem applies to both steam and ethylene oxide sterilization since the sterilizing agent cannot come into direct contact with the portion of the needle covered or otherwise shielded by the sleeve-closure unit. While this problem can possibly be obviated by employing ionizing radiation as the sterilizing means for the syringe-needle assembly unit wherein the needle is covered by the sleeve-closure unit, such sterilizing means are not generally applicable to commonly used disposable glass injection syringes since these means cause the glass to darken.
The concern about the possible lack of sterility in pre-filled syringe-needle units can be seen from the special attention this problem has received in the United States Pharmacopeia (USP) XX and XXI. In the Sterility Test chapter of the USP appears the following statement:
"Pre-Filled Disposable Syringes--Special attention should be directed towards demonstrating that the outside of the needle (that portion that enters the patient) is sterile."
A number of patents cover certain methods or structural features for sterilizing syringe-needle assembly units but these methods and/or structural features do not relate to the syringe-needle assembly units wherein the needle is imbedded in sleeve-closure units. These patents include U.S. Pat. Nos. Re. 25,113; 2,375,929; 2,646,043; 3,122,747; 3,370,588; 3,381,813; 4,148,316 and 4,240,425. These patents provide means for contacting the needle with sterilizing gases; e.g. steam or ethylene oxide, but these means are not suitable for pre-filled syringe-needle assembly units.