The use of isolator technology to fill and lyophilize pharmaceuticals presents many logistical challenges. Aventis Pasteur has developed procedures to fill, partially stopper, freeze-dry and cap its products in the Pilot Plant using three isolators (Transfer, Filling, and Lyophilizer). The equipment was designed to fit into an existing space, which also presented some significant challenges. The equipment has been installed and validated for the aseptic filling and freeze-drying processes for clinical supplies.
The traditional method of preparing the investigational supplies was filling on the licensed filling line in Manufacturing, or hand filling in the pilot plant. Recent FDA initiatives, requiring a notification and associated validation requirements for filling of non-licensed products on a licensed filling line has made this quite cumbersome and at times not possible, as with live vaccines. Also the scheduling of these non-licensed products to be filled on the manufacturing line prevented the flexibility needed to meet the clinical requirements.
Another consideration was the scale of the commercial filling line. Quite often the volume of the clinical vaccine approached the hold-up volume of the commercial filling line, thus product losses would be unacceptable.
While hand-filling operations were easy to perform and schedule with virtually no losses due to scale, the reduced sterility assurance made this option less attractive. Contract filling manufacturers was another option we explored, however the number of contract fillers was limited and very few would fill live material.