SYSTEMS AND METHODS FOR PRODUCING STERILE INJECTION DEVICES
The present disclosure provides novel processes for providing sterile, pre-filled syringes or injection devices for pharmaceutical compositions, including protein and biopharmaceutical formulations. In some examples, secondary packaging is performed in an aseptic environment, which removes the need for any terminal sterilization method. In some examples, the aseptic packaging method results in a sterile injection device suitable for use in ophthalmic injections.
1 . A method for providing an aseptically-packaged sterile, pre-filled injection device, comprising:
introducing an injection device comprising injection device components into an aseptic environment;
introducing a sterile ophthalmic pharmaceutical composition into the aseptic environment or sterilizing an ophthalmic pharmaceutical composition in the aseptic environment;
filling a body of the injection device with the sterile ophthalmic pharmaceutical composition in the aseptic environment to produce a sterile filled injection device body;
stoppering the sterile filled injection device body in the aseptic environment to form a sterile stoppered pre-filled injection device; and
packaging and sealing the sterile stoppered pre-filled injection device into packaging in the aseptic environment to produce the aseptically packaged sterile pre-filled injection device.
2 . The method of claim 1 , wherein the packaging is thermoformed in the aseptic environment.
3 . The method of claim 1 , comprising sterilizing the packaging and then introducing the sterilized packaging into the aseptic environment prior to the packaging step.
4 . The method of claim 1 , wherein sterilizing the ophthalmic pharmaceutical composition in the aseptic environment comprises passing the ophthalmic pharmaceutical composition through an in-line sterile filter having a pore size of 0.22 micron or less.
5 . The method of claim 1 , wherein the packaging and sealing step is performed directly after the stoppering step.
6 . The method of claim 1 , wherein the aseptically packaged sterile pre-filled injection device is not subjected to a terminal sterilization step.
7 . The method of claim 1 , wherein the aseptic environment comprises a sterile processing facility with a positive pressure air filtration system.
8 . The method of claim 1 , wherein the introducing step, the sterilizing step, the filling step, the stoppering step, and the packaging and sealing step are performed by a worker wearing a sterile garment.
9 . The method of claim 8 , wherein the sterile garment is disposable or wherein the sterile garment is sterilized between uses.
10 . The method of claim 8 , wherein the sterile garment comprises a synthetic fabric constructed from non-woven filaments, and is at least one of: non-linting, anti-static, chemical resistant, non-flammable, and/or liquid-proof, optionally wherein the synthetic fabric comprises at least one of polyester, Teflon laminated fabric, and/or Tyvek.
11 . The method of claim 1 , wherein the ophthalmic pharmaceutical composition comprises a VEGF antagonist and an excipient.
12 . The method of claim 1 , wherein the ophthalmic pharmaceutical composition comprises ranibizumab and an excipient.
13 . The method of claim 1 , wherein the ophthalmic pharmaceutical composition comprises aflibercept and an excipient.
14 . The method of claim 1 , wherein the injection device components further comprise a sterile plunger, a sterile plunger rod, or both.
15 . The method of claim 14 , wherein at least one of the body of the injection device, the sterile plunger, and the sterile plunger rod is sterilized by treatment with ethylene oxide prior to the introducing step.
16 . The method of claim 14 , wherein at least one of the body of the injection device, the sterile plunger, and the sterile plunger rod is sterilized by treatment with steam prior to the introducing step, or wherein at least one of the body of the injection device, the sterile plunger, and the sterile plunger rod is sterilized by treatment with radiation prior to the introducing step.
17 . The method of claim 1 , wherein the pre-filled injection device is a pre-filled syringe.
18 . The method of claim 1 , wherein the packaging comprises blister packaging or is a pouch.
19 . The method of claim 7 , wherein the sterile processing facility is a Restricted Access Barrier System with an ISO rating of Class 5 or higher, a Restricted Access Barrier System with an ISO rating of Class 7 or higher, or an isolator with an ISO rating of Class 8.
20 . The method of claim 1 , wherein at least one step selected from the group consisting of the introducing step, the sterilizing step, the filling step, the stoppering step, and the packaging and sealing step is performed robotically.
21 . The method of claim 1 , wherein introducing the sterile ophthalmic pharmaceutical composition into the aseptic environment comprises filter sterilizing the ophthalmic pharmaceutical composition into a sterile bag outside of the aseptic environment and then introducing the sterile bag containing the sterile ophthalmic pharmaceutical composition into the aseptic environment.