The Ongoing Success Of Prefilled Syringes

This article is part of a special feature on injectables that was published in the February issue of PTE Digital, available at http://www.pharmtech.com/ptedigital0211.

Prefillable syringe systems are still one of the strongest growing segments in the pharmaceutical primary packaging market. They are an ongoing success story in the industry and have been available for almost 20 years. Also in the coming years, many new drug products will be protein-based (biopharmaceuticals). Injection will be the main route of application for these products, providing further commercial opportunities for prefilled syringes. Another main driver for the continued uptake of prefilled syringes are the numerous benefits they offer compared with vials, such as ease of use and ease of administration.

Claudia Petersen. Director Business Development at Gerresheimer Tubular Glass.

Manufacturing challenges

Manufacturing steps such as washing, siliconisation and sterilisation of syringes prior to filling, used to be performed by the pharmaceutical company itself. Now, however, these steps are often performed by the supplier. This is advantageous for the pharma company because it does not need to invest in new equipment and validation.

Quality requirements regarding prefillable syringes are continuously on the rise because of the increase in more sensitive drug products. Additionally, there is ongoing interest from pharma companies in increasing their process yields. These demands impact all steps of the syringe manufacturing process, including glass forming, needle assembly (if applicable) and ready‑to‑fill processing. In the case of glass prefillable syringes, needle assembly and ready‑to-fill processing must take place under cleanroom conditions. The glass forming process is performed in an uncontrolled area, but manufacturers are working continuously to implement process improvements that increase product cleanliness, such as adding in-line washing steps. The manufacture of prefilled plastic syringes (mostly made from cyclic olefins) is completely performed under cleanroom conditions.

Glass syringes are sterilised using ethylene oxide (ETO) in accordance with ISO 11135. Gamma irradiation would be an alternative solution, but this would lead to glass discolouration. Currently available prefilled syringes are sterilised using gamma or e‑beams, with material properties determining the sterilisation method. ETO sterilisation is possible, but requires a highly intense evaluation of the long‑term impact of the process on the material properties with regards to potential interactions between ETO and the polymer. This could create leachables and impact the quality of the final drug product.

Manufacturers of prefilled syringes will have to validate their chosen sterilisation process, as well as the packaging. Depending on the supplier, the sterility of the unused product is certified for about 3–5 years.

With regard to overall product quality, important considerations include leachables, glass breakage and cosmetic defects. Continuous process improvements can be used to address different solutions for one topic. In the case of leachables, for example, leachables can be generated by the glass itself, the elastomer compounds, (e.g., tip cap/needle shield and plunger stopper), the syringe bore forming process (tungsten) and the needle assembly process (needle glue leachables). Solutions could be to use a tungsten-free syringe bore forming process or to optimise the needle mounting process to minimise leachables from glue residuals. To fulfill quality demands regarding cosmetic defects, the capabilities of vision inspection systems can be improved. In addition, process equipment must be developed and adjusted for the optimal transport and handling of the syringe barrels during the forming process to prevent scratches and other cosmetic defects.

Where is innovation required?

A large number of competitors are moving into the area of prefilled syringes, so it is important for companies to differentiate their products. As well as addressing the issue of leachables and cosmetic defects, and offering superior quality, product differentiation can be achieved by offering in‑depth technical support to address customer specific needs.

One area of improvement for glass prefillable syringe systems is the inclusion of syringe accessories to further increase product safety, such as rigid needle shields, safety devices to prevent needle sticks after administration and specific luerlock closure systems.

Improvements can also be made in the area of lubricants. Currently, glass prefilled syringes tend to use medical-grade silicone oils as lubricants to provide the required functionality regarding break loose and gliding forces. These oil coatings release small droplets, which contribute to the overall particle load of the final drug product. In the case of protein-based drug products, these lubricants may also cause aggregation. Because of this, determining alternative coatings to replace silicone oil will be an important area for future improvement.

www.gerresheimer.com