System for filling and assembling pharmaceutical delivery devices

Abstract

The present invention provides for an assembly for filling and capping a barrel of a pre-filled syringe. The assembly includes a syringe body having a neck end, a rimmed end, and a side wall extending between the neck end and rimmed end. The body has an outer surface and an inner surface. The assembly includes a piston having an upper surface, a lower surface, and a side surface extending between the upper and lower surfaces. The inner surface of the body and the side surface of the piston is in contact to form a liquid impermeable seal. The assembly further includes a stabilization member that at least partially surrounds and contacts the outer surface of the body. The stabilization member is positioned proximate the rimmed end of the body to provide additional mass thereto in an amount sufficient to permit the assembly to be conveyed freestanding in a longitudinally upright position on the stabilization member through an apparatus for filling and capping pharmaceutical vials. Methods for producing a pre-filled syringe barrel are also provided.

1 . An assembly for filling and capping a barrel of a pre-filled syringe, the assembly comprising: 
 a) a syringe body having a neck end, a rimmed end, and a side wall extending between the neck end and rimmed end, the body having an outer surface and an inner surface;    b) a piston having an upper surface, a lower surface, and a side surface extending between the upper and lower surfaces, the inner surface of the body and the side surface of the piston in contact to form a liquid impermeable seal; and    c) a stabilization member that at least partially surrounds and contacts the outer surface of the body, the stabilization member is positioned proximate the rimmed end of the body to provide additional mass thereto in an amount sufficient to permit the assembly to be conveyed freestanding in a longitudinally upright position on the stabilization member through an apparatus for filling and capping pharmaceutical vials.    
   
   
       2 . An assembly according to  claim 1 , wherein the stabilization member comprises a sleeve, the sleeve has a top end and a base end, and the rimmed end of the body is positioned within the sleeve proximate the base end of the sleeve.  
   
   
       3 . An assembly according to  claim 2 , wherein the base end of the sleeve has a radially projecting flange.  
   
   
       4 . An assembly according to  claim 3 , wherein the flange has a substantially flat outwardly facing wall that is substantially vertical when the assembly is standing longitudinally upright.  
   
   
       5 . An assembly according to  claim 2 , wherein the stabilization member further comprises a stabilization cap having a hollow portion with an upper end and a lower end, the lower end having a finger flange that extends radially outwardly therefrom, the hollow portion is sized to closely fit within the body, and the finger flange is sized to fit within the base end of the sleeve.  
   
   
       6 . An assembly according to  claim 1 , wherein the piston comprises a material that is impermeable to liquid and sufficiently permeable to a sterilizing gas to permit sterilization of the seal between the inner surface of the body and the side surface of the piston upon exposure to a sterilizing gas.  
   
   
       7 . An assembly according to  claim 1 , wherein the piston comprises neoprene.  
   
   
       8 . An assembly according to  claim 1 , wherein the piston comprises a material that is substantially resistant to the effects of at least one standard cycle of gamma radiation.  
   
   
       9 . An assembly according to  claim 1 , wherein the piston comprises bromo-butyl rubber.  
   
   
       10 . An assembly according to  claim 9 , wherein the syringe body comprises cerium oxide in an amount sufficient to prevent discoloration of the body upon exposure to at least one standard cycle of gamma radiation.  
   
   
       11 . An assembly according to  claim 9 , wherein the syringe body comprises about 1 wt % cerium oxide based on the total weight of the syringe body.  
   
   
       12 . A method for producing a barrel for a pre-filled syringe, comprising: 
 a) providing a syringe body having a neck end, a rimmed end, and a side wall extending between the neck end and rimmed end, the body having an outer surface and an inner surface;    b) providing a piston having an upper surface, a lower surface, and a side surface extending between the upper and lower surfaces;    c) providing a stabilization member; and    d) forming an assembly comprising the syringe body, the piston, and the stabilization member such that: (i) the inner surface of the body contacts at least a portion of the side surface of the piston to form a liquid impermeable seal; (ii) the stabilization member at least partially surrounds and contacts the outer surface of the body; and (iii) the stabilization member is positioned proximate the rimmed end of the body to provide additional mass thereto in an amount sufficient to permit the assembly to be conveyed freestanding in a longitudinally upright position on the stabilization member through an apparatus for filling and capping pharmaceutical vials.    
   
   
       13 . A method according to  claim 12 , wherein the syringe body provided in step (a) is pre-sterilized, the piston provided in step (b) is pre-sterilized, and the stabilization member provided in step (c) is pre-sterilized and steps (a)-(d) are performed in an aseptic environment.  
   
   
       14 . A method according to  claim 13 , further comprising, subsequent to step (d), the step of (e) overwrapping the assembly with an overwrap material in an aseptic environment to maintain sterility.  
   
   
       15 . A method according to  claim 14 , further comprising, subsequent to step (e), the steps of: 
 f) removing the overwrap;    g) filling the body with at least one pharmaceutical component through the neck end using the apparatus for filling and capping pharmaceutical vials; and    h) capping the neck end of the body using the apparatus for filling and capping pharmaceutical vials.    
   
   
       16 . A method according to  claim 15 , wherein the at least one pharmaceutical component is in the form of a solid when filled into the body.  
   
   
       17 . A method according to  claim 15 , wherein the at least one pharmaceutical component is in the form of a liquid when filled into the body.  
   
   
       18 . A method according to  claim 17 , further comprising, subsequent to step (g) and prior to step (h), the step of lyophilizing the at least one pharmaceutical.  
   
   
       19 . A method according to  claim 12 , further comprising, prior to step (b), the step of selecting a material for the piston that is impermeable to liquid but sufficiently permeable to a sterilizing gas to permit sterilization of the seal between the inner surface and the body and the side surface of the piston upon exposure to a sterilizing gas.  
   
   
       20 . A method according to  claim 19 , further comprising, subsequent to step (d), the step of (e) overwrapping the assembly with an overwrap material.  
   
   
       21 . A method according to  claim 20 , further comprising, subsequent to step (e), the step of (f) sterilizing the barrel with a sterilizing gas.  
   
   
       22 . A method according to  claim 21 , further comprising, subsequent to step (f), the steps of: 
 g) removing the overwrap;    h) filling the body with at least one pharmaceutical component through the neck end using the apparatus for filling and capping pharmaceutical vials; and    i) capping the neck end of the body using the apparatus for filling and capping pharmaceutical vials.    
   
   
       23 . A method according to  claim 22 , wherein the at least one pharmaceutical component is in the form of a solid when filled into the body.  
   
   
       24 . A method according to  claim 22 , wherein the at least one pharmaceutical component is in the form of a liquid when filled into the body.  
   
   
       25 . A method according to  claim 24 , further comprising, subsequent to step (h) and prior to step (i), the step of lyophilizing the at least one pharmaceutical.  
   
   
       26 . A method according to  claim 12 , further comprising, prior to step (b), the step of selecting a material for the piston that is sufficiently resistant to at least one cycle of gamma radiation.  
   
   
       27 . A method according to  claim 26 , further comprising, prior to step (a), the step of selecting a material for the syringe body material that comprises cerium oxide in an amount sufficient to prevent discoloration of the body upon exposure to at least one cycle of gamma radiation.  
   
   
       28 . A method according to  claim 27 , further comprising, subsequent to step (d), the step of (e) overwrapping the assembly with an overwrap material.  
   
   
       29 . A method according to  claim 28 , further comprising, subsequent to step (e), the step of (f) sterilizing the barrel with at least one cycle of gamma radiation.  
   
   
       30 . A method according to  claim 29 , further comprising, subsequent to both steps (f) the steps of: 
 g) removing the overwrap;    h) filling the body with at least one pharmaceutical component through the neck end using the apparatus for filling and capping pharmaceutical vials; and    i) capping the neck end of the body using the apparatus for filling and capping pharmaceutical vials.    
   
   
       31 . A method according to  claim 30 , wherein the at least one pharmaceutical component is in the form of a solid when filled into the body.  
   
   
       32 . A method according to  claim 30 , wherein the at least one pharmaceutical component is in the form of a liquid when filled into the body.  
   
   
       33 . A method according to  claim 32 , further comprising, subsequent to step (h) and prior to step (i), the step of lyophilizing the at least one pharmaceutical.  
   
   
       34 . A method for producing a pre-filled syringe barrel, comprising: 
 a) providing a sterile assembly comprising a syringe body having a neck end, a rimmed end, a side wall extending between the neck end and the rimmed end, an outer surface and an inner surface, a piston having an upper surface, a lower surface, and a side surface extending between the upper and lower surfaces and a stabilization member, the sterile assembly formed such that: (i) the inner surface of the body contacts at least a portion of the side surface of the piston to form a liquid impermeable seal; (ii) the stabilization member is at least partially surrounds and contacts the outer surface of the body; and (iii) the stabilization member is positioned proximate the rimmed end of the body to provide additional mass thereto in an amount sufficient to permit the assembly to be conveyed freestanding in a longitudinally upright position on the stabilization member through an apparatus for filling and capping pharmaceutical vials;    b) filling the body with at least one pharmaceutical component through the neck end using the apparatus for filling and capping pharmaceutical vials; and    c) capping the neck end of the body using the apparatus for filling and capping pharmaceutical vials.    
   
   
       35 . A method according to  claim 34 , further comprising, prior to step (b), the step of maintaining the assembly in an aseptic environment until it is ready to be filled through the neck end of the body with the at least one pharmaceutical component.  
   
   
       36 . A method according to  claim 35 , wherein steps (b) and (c) are performed in an aseptic environment.  
   
   
       37 . A method according to  claim 36 , wherein the at least one pharmaceutical component is in the form of a solid when filled into the body.  
   
   
       38 . A method according to  claim 36 , wherein the at least one pharmaceutical component is in the form of a liquid when filled into the body.  
   
   
       39 . A method according to  claim 38 , further comprising, subsequent to step (b) and prior to step (c), the step of lyophilizing the at least one pharmaceutical.