Key Points - Pre-filled syringes reduce accidents and dose errors. - Plastic is competing with glass, especially for niche biotech products. - Cycloolefin-copolymers offer distinct advantages: low water vapour permeability, high transparency, scratch resistance and the ability to withstand final steam sterilisation.
Paljit Mudhar, a research analyst in Frost & Sullivan’s pharmaceuticals and biotechnology, healthcare (EMEA) division examines the the latest developments in disposable medical products with a closer look at the future of pre-filled syringes.
Recent years have seen a movement towards plastic and disposable syringes so that the needle is protected and cannot be re-used. This has stimulated the demand for convenient and safe pre-filled syringes over conventional glass vials for packing parenteral drugs. Parenteral packaging innovations and applications have made devices easier to use for both the healthcare professional and the patient. Due to technological advances, pre-filled syringes are one of the fastest expanding growth opportunity areas and stand to make strong gains, along with other specialised drug delivery systems such as drug-eluting stents, especially with the developments of advanced polymers and plastics.
Pre-filled syringes have actually been around for more than two decades. The European market, worth $300m and growing at between 8 and 10 per cent annually, is relatively mature compared to that of the US. The pre-filled syringe market worldwide is dominated by three or four key players. Becton, Dickinson & Co (BD) is the market leader in Europe, with a significant gap between it and the number two player, Buender Glas (a subsidiary of Gerresheimer). MGlas and Schott forma vitrum are third and fourth, respectively, but with an extremely large gap between them and Buender Glas.
The global market for pre-filled syringes has seen healthy growth in recent years as the pharmaceutical industry has grown and become more sophisticated. Pre-filled syringe manufacturers have therefore had to respond to increasing demand, new requirements and more sophisticated forms of drug delivery.
New products are being put in syringes now. Pre-filled syringes are used to package injectable drugs and diluents. Some of the categories of drugs packaged in pre-filled syringes include vaccines, blood stimulants, therapeutic proteins, erythroproteins, interferons, and rheumatoid arthritis medication. Many new injectable products are being pre-filled, with security being the main reason why.
Health and Safety
It is estimated that healthcare workers in Europe suffer one million needle injuries each year, of which 40 per cent relate to nurses. Conventional syringes can increase the amount of accidents that occur because the needle tip is exposed for longer while the user prepares it. Many pre-filled syringe manufacturers now incorporate safety elements into the design of the device. These can reduce the risk of needle injuries. As more medications are self-administered at home, safety becomes an important driver, more so than convenience and ease of use.
Pre-filled syringes essentially eliminate the processes that are required before you use a drug in a vial. Additionally, they help eliminate dosing errors, because pre-filled syringes contain the exact dose. Many pharmaceuticals manufacturers overfill vials by up to 25 per cent to make sure the end-user is guaranteed to withdraw the dose required. However, this overfill can cause errors that are virtually removed with pre-filled syringes. With the advent of more biotech drugs, this is advantageous, as it means less waste, especially if some vaccines are in short supply or are really expensive.
Glass vs Plastic
The interest in the use of plastic in the pre-filled syringe area has increased, especially in 2004–05, although its application has been limited to large volumes (20–50ml typically). Plastic has unique properties, which allow for its use in niche areas and specific applications. It will still be some time before plastic syringes can truly compete, but plastic represents a growing market, especially for larger syringes, for which it is difficult to use glass.
Essentially, the unit prices of plastic and glass are similar, so price advantages are not driving this area. The major advantage of plastic is that it does not break, has fine tolerance and can provide more accurate doses. Some additional product properties include a moisture barrier and impact resistance. The rigidity of glass means that there is a limited set of things that can be done with it. By developing a polymer to do the same as glass, it is possible to engineer a lot of design features that could not be done with a glass syringe.
Interaction of Drug and Packaging
One major challenge for manufacturers is the interaction of pre-filled syringes with the drug. This causes great concern because it creates stability issues. Manufacturers need to eliminate any interaction between drugs and packaging materials. Regulatory bodies, companies and customers will scrutinise every aspect of needles and syringes, so processing and quality control issues are crucial.
Glass syringes have typically been used in the pre-filled syringes sector because of their high chemical resistance and low moisture permeability. The barrier properties of glass make it the ideal package for parenteral products and it has always been considered less reactive than plastic with parenteral products, having lower levels of leachables and extractables.
For some products, however, such as new biotechnology drugs, this is not the case. Though usually considered highly non-reactive, glass contains trace amounts of alkali ions, which can leach out. This is supposed to have a significant impact on some sensitive new drugs. Glass suffers from protein adsorption, which can lead to protein denaturation, where the molecule loses its three-dimensional structure and forms partially unfolded intermediates. The protein denaturation is followed by chemical degradation and protein aggregation. Copolymers have changed the equation drastically by reducing the chemical interaction between the drugs and containers.
Another drawback of glass is that when used in storage containers for water (WFI), which is a common dilutent for reconstituting lyophilised formulations, it releases hydroxide ions, making it difficult to maintain the pH within the limits set out in the US and other pharmacopoeias. Additionally, glass does not offer the design flexibility plastics offer and are not breakage-resistant.
Cycloolefin-copolymers (COCs) are glassclear amorphous copolymers based on cyclic and linear olefins. These materials form a family of engineering resins that exhibit a unique combination of properties, including high transparency,low density, excellent moisture barrier capabilities and resistance to aqueous and polar organic media. Topas® COC is being used for pre-filled syringes, needleless injectors and other drug delivery systems.
COC is now challenging glass within the pre-filled syringe market, because of its technical qualities. This is because as biotechnology drugs are being used more often, glass becomes more of an obstacle as it can interact with the drugs. COC’s properties have addressed this balance. This has enabled pre-filled syringe manufacturers to provide pharmaceutical companies and other end-users with more flexible drug delivery solutions. Schott forma vitrum, for example, has a Top Pac pre-filled syringe designed to meet process requirements, which include low water vapour permeability, high transparency, scratch resistance and the ability to withstand final steam sterilisation.
However, despite initial high expectations for COC, it has struggled to gain a foothold in the marketplace because of high cost, and an extremely challenging economic climate. Application development is also taking much longer than anticipated because of the tight regulations in pharmaceutical packaging. Plastic materials are more complex than glass. Also regulatory guidelines mean manufacturers and end-users are not as keen to shift from glass to plastics. However, if some of the application developments currently in the pipeline come to fruition, then polymers can expect a brighter future.