Nitrogen Dioxide Biodecontamination: A New, Effective and Cost-saving Option for Biodecontaminating Syringe Tubs Prior to the Filling Line

by David Opie, PhD; Maura O.Kahn (Noxilizer)

The prefilled syringe market continues to grow. In the past, products that are not andidates for oral administration (like large molecule compounds) would be delivered in a multi-dose vial container. Today, many of these products are administered in prefilled syringes to  reduce the risk of injury to health care workers administering the drug, to reduce the container overfilling, and to improve dosing accuracy (Daedal Research, 2013).
To meet the growing demand, companies install small, medium and high-speed filling lines, depending on production needs. The majority of filling lines installed each year are small to medium speed lines, filling 100 to 200 syringes per minute, or about 1 to 2 syringe tubs per minute (Lysfjord, et al., 2010). These filling lines are used for commercial product, clinical trial or pre-clinical products. High-speed filling lines are typically reserved for large volume products, where the filling lines can fill syringes at a rate of six tubs per minute.
These filling lines rely on sterile, clean and ready-to-fill syringes that are packaged in tubs. Glass or polymer syringes are manufactured and placed in these (polystyrene) tubs for shipping. Typically, there are 100 syringes in a tub. These tubs are sealed with a Tyvek lid, forming a sterile barrier. Once the lid is applied, the tub is placed in an outer bag for additional protection, then placed in a carton. The syringes packaged in cartons are sterilized via ethylene oxide or gamma radiation and shipped to the site for filling.
Automated methods of introducing the syringes into the isolated filling line include a biodecontamination process after the tubs are removed from the outer bags. For smaller filling lines, the usual process for introducing the syringes into the filling line includes the following steps: biodecontaminating the outside of the sterile barrier bag (or tub depending on the process), debagging the syringe tub, and de-lidding (removing the Tyvek lid from the tub). The de-lidding and aseptic filling will occur in a Grade A (ISO 5, Class 100) isolator. However, prior to the biodecontamination, the tubs of sterile syringes (either within bags or removed from bags) occurs in a less-controlled area, such as a Grade B or Grade C (ISO 7 or 8, respectively) area. Therefore, the risk of microbial contamination of the outer surface exists, which necessitates a biodecontamination step prior to lid removal and aseptic filling (Mouldenhauer, 2013). In this document, the methods of syringe tub biodecontamination are reviewed before describing nitrogen dioxide (NO2) as a beneficial option for the biodecontamination of syringe tubs prior to introducing the tubs into the filling line.

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