Last month, the US Food and Drug Administration approved Novartis’s (Basel) meningitis vaccine Menveo, and Health Canada approved Merck’s (Whitehouse Station, NJ) Gardasil vaccine for human papillomavirus. These developments demonstrate recent advances in biologicals and indicate the drugs’ importance for the industry’s future. Most biopharmaceuticals are liquid products delivered through injections. To find out about the process of manufacturing prefilled syringes, and to learn about innovations in filling lines, Equipment and Processing Report talked to Thomas Otto, managing director of Vetter (Ravensburg, Germany), a company that specializes in aseptically prefilled syringe systems, cartridges, and vials.
EPR: What are the advantages of prefilled syringes?
Otto: The advantage is that prefilled syringes are ready for injection. The product is inside the container in the right volume and the right dosage. The user only has to open the syringe and initiate the injection. He or she doesn’t have to prepare a vial or take the product out into a syringe system—everything is prepared in place. Prefilled syringes support active-ingredient yield and correct dosage.
Prefilled systems have a big advantage for freeze-dried products. If you have a freeze-dried vial, you have the solvent, for example, in a separate syringe. If you have a dual-chamber syringe, this enables less overfilling. So costs clearly can be reduced, especially when it comes to the high-value substances.
EPR: Are prefilled syringes limited to certain types of products?
Otto: In principle, there is no limitation to prefilled syringes. We at Vetter fill various types of product. It doesn’t matter whether it’s a biotechnology product, a vaccine, or anything else. Only a few products such as high-viscosity products can’t be filled into a prefilled syringe. Some products are not stable in liquid form over a long time. You can freeze dry them and keep the active drug and the solvent separately in dual-chamber syringes.
Thomas Otto, managing director of Vetter
EPR: What processing options do drugmakers have if they want to present their products in prefilled syringes?
Otto: They have two main concepts. The first concept is bulk processing—the firm that’s doing the filling gets all the packaging components and prepares them itself for filling. This includes washing, siliconization, and sterilization. This technology requires a lot of knowhow and capital investment on one hand, but it gives the pharmaceutical manufacturer control of the process. Bulk processing is fully scalable and available for high-speed and high-volume filling, as well as small-scale clinical production. It gives the manufacturer flexibility, but it’s a complex process.
The other process uses presterilized systems such as the Sterile Clean Fill system from BD (Franklin Lakes, NJ). In this system, syringes and stoppers arrive at the filling site already prepared and sterilized. The advantage is that the filler does not have to prepare the packaging components, but only to fill the product. On the other hand, if you control the preparation process, you’re much more flexible because you can use the right amount of silicone and the right stopper treatment for your product. The presterilized parts are treated by chemical sterilization processes such as ethylene oxide. Rubber stoppers are gamma irradiated, which might cause a particle problem. If you have the preparation process in house, you can perform heat sterilization or other methods.
EPR: Does Vetter use bulk processing or presterilized systems?
Otto: We have both processes here in house. We understand the advantages of both systems.
EPR: Has Vetter incorporated robots into its operations?
Otto: Vetter has been using robots for transferring components for many years. Vetter’s experience with robots is excellent because they remove all need for manual processes. We have highly automated bulk lines; all manual transfers have been removed all the way from the detraying of the untreated syringes to the filled syringes and delivery trays.
EPR: Does Vetter use disposable components in its processes?
Otto: Vetter has designed a new filling line for preclinical, Phase I, and Phase II in our new plant in Skokie, Illinois, where we use a lot of disposable technology such as vessels, preparation tanks, and filling needles. Stainless-steel vessels cost a tremendous amount of money and takes a lot of time, therefore, disposable technology is interesting.
EPR: Is disposable technology more popular in clinical phases than it is in manufacturing?
Otto: Today, yes. If you’re thinking about high-volume production and you’re doing the production every day, it makes a lot of sense to use stainless-steel containers and filling needles. But if you need a component one time or only a few times, then it makes a lot of sense to use disposable technology. I’m sure that both technologies will have their place in the biopharmaceutical industry, but disposable technology is growing in popularity.