Filling Pre-sterilized Containers

Pre-sterilized, nested syringes are an alternative to bulk syringes that must be sterilized at the filling line. As the injectables market grows globally, there is growing use of pre-sterilized syringes because they are "off-the-shelf" systems, comments Kevin Wrigley, product and service manager at Vetter. Bulk syringes, which offer more flexibility, remain in high demand for products with specific primary packaging requirements. "Pre-sterilized syringes offer standardized systems and are often easier to handle because of the tubs they are nested in," says Wrigley. "Bulk syringes on the other hand, offer a wider range of choices for product-specific processes or primary packaging material like closure components. Ultimately, the decision regarding the drug-delivery system will depend on the specific filling requirements of the product, market volume, and the business strategy of the pharma/biotech company when launching a product." Choosing the most suitable packaging should begin in the earliest clinical stages, adds Wrigley. "Once a drug manufacturer has decided on a pre-sterilized system, process adjustments or format changes might be limited because of the pre-set packaging and tub characteristics."

Advantages of pre-sterilized syringes include lower investment costs and smaller-footprint equipment for filling and closing. Fewer processing steps and less handling help reduce damage. "Since syringes are even more prone to damage and much more difficult to transport than other glass containers, they were the first packaging type to be offered as pre-sterilized solution in nests," notes Klaus Ullherr, product manager at Bosch Packaging Technology.

Pre-sterilized vials and cartridges
Pre-sterilized vials or cartridges are now also available, and, to date, are typically used in smaller batches, such as in formulation and development laboratories, according to Markus Hörsch, sales and marketing director at Bausch+Ströbel. The company's SFM 5110 filling system is designed for these applications and processes all pre-sterilized containers (vials, cartridges, or syringes) in nests inside tubs.

Schott's adaptiQ system for ready-to-use pharmaceutical vials consists of a patented nest that securely holds up to 100 clean and sterile vials in an industry-standard tub. It is suitable for both small and large batches, and is advantageous for smaller batches because it minimizes setup time for packaging changes. Besides simplifying the process, the nested packaging protects the glass containers from scratches caused by vial-to-vial and vial-to-machine contact, which reduces the reject rate and also preserves the cosmetic quality of the vials, noted the company in a press release. Schott is advancing to full-scale production at its US facility, the company announced in a Jan. 12, 2015 press release.  

Bosch recently launched a filling and closing machine for pre-sterilized nested syringes, vials, and cartridges. "The FXS Combi is the first machine of its kind with an integrated capping station for vials and cartridges," says Ullherr. "The capping of vials and cartridges takes place directly after the stopper insertion. This ensures the highest pharmaceutical safety, as the container is immediately and safely closed after filling."

Challenges

A challenge in setting up a line for pre-sterilized syringes is how to transfer the sterile syringes to the point of filling without compromising sterility. Syringes, nested in tubs, are sealed with a plastic layer and also protected by a bag. Combining the filling and closing machine with an upstream tub and bag opener eliminates contamination risk, notes Ullher.

Although most syringes are glass, plastic syringes are also available pre-sterilized. Some small adjustments might need to be made to filling and closing machines to handle plastic syringes. "Depending on the plastic material, plastic can be more delicate and requires a gentler handling," notes Ullherr. "Plastic syringes might require a centering plate made of plastic instead of metal, and they can also have a slightly different diameter than glass syringes."

Product changeover
For changing from one product to another in filling equipment, manufacturers can choose from clean-in-place/sterilize-in-place (CIP/SIP) systems and single-use, disposable systems. "The use of CIP/SIP is recommended for the production of large batches and toxic products, while contract manufacturers and smaller batches will work with single-use systems, as they can eliminate the loss of capacity resulting from lengthy cleaning validation as well as the risk of contamination between batch runs," comments Ullherr. In 2014, Bosch expanded its PreVAS prevalidated, pre-assembled, and pre-sterilized single-use filling systems, which the company developed in cooperation with Sartorius Stedim Biotech. For example, a new mobile filling station can be combined with existing filling lines. In this version, the product bag is situated outside of the isolator, and the filling tubes are guided through the isolator wall using a newly developed multi-tubing port, before being connected to the filling station, Bosch said in a press release.