In the pharmaceutical industry, the usage of Prefilled Syringes is increasing and is further expected to accelerate. Prefilled syringes minimize drug waste, increase the product life span and are convenient to use. The completely assembled syringe needs to be sterilized and then packaged for later use to ensure sterility at the point of use.

Terminal sterilization of prefilled syringes requires meticulous engineering owing to the sensitivity of the drugs and the packaging material used. There should be no change in the drug, packaging material or any interaction between the two when sterilizing the liquid pharmaceuticals.

Challenges in Terminal Sterilization

Ventilator Sterilization employs the steam-air mixture for sterilization operation and requires special combination of sterile-filtered compressed air and pure steam in a homogenized form throughout the sterilization cycle. As the operation is likely to occur in an isochoric change of state, it becomes imperative to establish a supporting pressure. This pressure can be adjusted such that it prevents deformation, container breakage, and stopper movement thus, ensuring integrity and dimensional stability.

In prefilled syringes, the inserted stoppers are not mechanically fixed with an aluminium cap. Due to this, inaccurate supporting pressure settings lead to breakage of the stopper and compromise sterility. Also, monitoring the plunger movement is of prime importance. This necessitates precise pressure regulation and monitoring to support the pressure on product.

Apart from the above, the syringe’s stability, material, dimensions of the stopper, and fill volume affect the stopper movement.

Another important consideration for terminal sterilization is the loading pattern of the syringes. The alignment pattern, position, packaging dictates the process efficacy. Special mounts are constructed for loading the prefilled syringes. Automated handling of the syringe loading is also being utilized. The constant flow of the steam/air mixture plays a key role for determining the loading pattern.

Terminal Sterilization: The Process

In the Ventilator Sterilizer, generation of counter pressure in the chamber balances the pressure inside the syringe.  This balance is achieved using sterile filtered air in the chamber.

The air present in the chamber is not removed in the initial phase. Control of the quantity of steam-air mixture is done by increasing or decreasing to maintain the pressure to avoid damage to the PFS.

Optimizing the required parameters, Pharmalab recently executed two successful projects for Terminal Sterilization.
In the Double-door Horizontal Sliding Ventilator Sterilizer, trials were performed using full loads with approximately 21,000 qty of 2 ml PFS. For another Mumbai-based pharmaceutical manufacturer, trials were performed in the Ventilator Sterilizer using the Rigid Needle Shield (RNS) and Luer Tip Luer Lock (LTLL) PFS.

For the above-mentioned trials, heat distribution study was performed wherein the temperature sensor was inserted in the PFS. On unloading, results indicated complete sterilization with all PFS being intact.
On analysis, the heat distribution was found to be within ± 1°C and the maximum plunger movement was observed to be less than 1 mm.