The parenteral drug market has long used 1 mL long glass prefilled syringes. While these syringes have experienced success, they have been prone to, for example, breakage or production inconsistencies. Increased regulatory scrutiny of glass syringes, vials and cartridges, and the way in which they are filled and processed, has led drug manufacturers to search for alternatives.
A few years ago, syringes of Crystal Zenith, a proprietary cyclic olefin polymer from Daikyo Seiko, were introduced. The polymer syringes are not only more resistant to breakage, but is known to have improved manufacturing consistency as well as resistance to extreme temperatures. In addition, they are silicone-free.
Recently, West Pharmaceutical Services and Vetter partnered to offer 1 mL Crystal Zenith syringes to their clients. Drug manufacturers have the option to conduct the syringe filling within their facility, or to outsource to Vetter. To find out more, we presented questions to West and Vetter. Responses were provided by Graham Reynolds, West’s VP for Marketing & Innovation; Mike Schaefers, West’s VP for Marketing in Europe; and Vetter Managing Director Thomas Otto.
PhM: West and Vetter have collaborated to provide customers with the new Daikyo Crystal Zenith syringes. What was the business rationale?
Graham Reynolds: Many of our customers are challenged to find total packaging solutions that are not only high-performance syringe systems, but also suitable for sensitive biopharmaceutical products. Many of today’s sensitive drug products present a host of new challenges: higher viscosity, sensitivity to tungsten and silicone oil, etc. Also, manufacturers are facing increased scrutiny from regulatory agencies while searching for a way to move drug products to the market quickly, maintaining safety and efficacy.
PhM: What do drug manufacturers need to know about the CZ syringes and the polymer of which they’re made? Are there new manufacturing issues or validation challenges to consider?
Mike Schaefers: The Crystal Zenith polymer offers many advantages, including glass-like transparency, which permits visual inspection of the manufactured components and of the parenteral products that are delivered to the end user. In addition, the material is highly break-resistant and forms an excellent moisture barrier. Packaging systems based on Daikyo Crystal Zenith have been used for many years on marketed drug products. The 1mL long insert needle syringe system features new enhancements such as automated cleanroom manufacturing, 100% vision inspection (including the needle), and an insert molding process for the needle that eliminates the need for adhesive or tungsten.
Graham Reynolds: We feel the syringe is ideally suited for biopharmaceutical drug delivery. It is sterile, silicone-oil-free and the plunger is laminated with Flurotec film, which helps to lower protein adsorption and serves as a barrier to leachable substances while enabling effective functionality without the need for silicone oil lubrication. The material’s tight dimensional tolerance and consistency of syringe functionality can help to make a delivery system’s operation predictable, which makes it an easy-to-use, safe option for the patient, as well as enabling consistent performance within a delivery device (such as an auto-injector).
In general terms, the Crystal Zenith syringes are provided in the same basic format as similar glass syringes, enabling filling on existing equipment. West works actively with customers to understand specific equipment needs, and has extensive links with the equipment manufacturers.
PhM: Were the regulatory issues with prefillable glass syringes the key driver for this project, or was performance and patient preference the driver?
Graham Reynolds: These syringes have been developed specifically to meet the needs of sensitive biologic products, and may help to overcome many of the limitations of glass syringes, including breakage and particulates, as well as eliminating materials such as silicone oil, tungsten and adhesive, which could be sources of potential interaction with certain drugs. The FDA is becoming increasingly aware of glass-related quality issues, including breakage, cracks, contamination and particulates (often formed over time due to interaction between the glass and the drug) and there has been an increase in the number of recalls related to glass issues. It was our goal to develop a system that meets the needs of the patient, the drug product and the drug manufacturer, and to be able to fill and deliver that product to the market as efficiently and effectively as possible.
Recent developments around the use of polymeric materials for drug containment have allowed delivery system companies to work closely with drug manufacturers to develop novel systems designed specifically to meet patient needs. The design and manufacturing flexibility of a polymeric drug container, combined with the ability to create patient-friendly devices designed with human factors engineering, enables the design of more innovative overall delivery systems that may aid in patient compliance through ease of use and enhanced technology.
PhM: When will commercial-scale filling be available? Do you expect manufacturers of commercialized products to look to switch syringes, or will the CZ syringes be used primarily for drugs in clinical trials?
Graham Reynolds: Syringe manufacturing capacity is in place today to support customer stability trials and initial activities, which will be required prior to full-scale commercial launch of a drug. West has sufficient capacity to meet these requirements, as well as initial scale-up, and has plans to introduce more capacity within our Scottsdale, Arizona, facility in the near future. Infrastructure is in place, and additional manufacturing cells will be added to ensure customer needs are met.