PharmTech: What key factors are influencing the injectable-drug market?
Reynolds : There are many factors affecting the growth of injectable-drug packaging and delivery today, most notably the continuing growth of biologic therapies, which are mostly injected, and the continuing growth of self-administered therapies for chronic conditions such as autoimmune diseases and diabetes. Challenges for these products can be split into two main areas: how to package and contain the drug to maintain safety, efficacy, and stability for an extended period of time and how to deliver these products in a way that ensures compliance, ease of administration (often away from a clinical environment), safety, and effectiveness.With regard to packaging, recent trends include the drive toward cleaner and more secure primary containment systems that avoid interaction with the drug product and maintain the drug product's purity and effectiveness over time. Component manufacturers continue to develop sophisticated packaging components and delivery systems to support the requirements of complex drug products. Today's components are meeting increasingly stringent standards for quality and cleanliness. Although the components have changed little in appearance, the material science and manufacturing technologies that go into their creation have undergone significant advance. Increasing use of fluoropolymer-coated elastomer products and advances in plastic materials has produced a variety of vials and syringes that will be of great importance for primary container closure systems and medical devices. Also, many new biologics will be packaged in a prefilled device (a syringe or cartridge), and many will require reconstitution prior to administration.
PharmTech: What are key developments in injectable-drug product forms?
Reynolds: Liquid-drug presentations packaged in prefilled syringes continue to be a preferred route of administration for many new biologics. Historically, most of these syringes have been made from glass. Glass syringes may have inherent weaknesses that can have a negative impact on sensitive biologic molecules, notably the presence of silicone oil, which is used as a lubricant, and tungsten and glue, which are introduced as part of the manufacturing process. Breakage issues can arise with glass syringes during handling or delivery to the patient, particularly when a syringe is combined with a device such as an autoinjector that can exert excessively high force on the glass syringe. Glass manufacturers are overcoming some of these limitations, and increased focus is being placed on plastic syringes.
Because of increased interest in self-administration, development in syringes, cartridges, autoinjectors, and pens continues. Areas of interest have been the growth of disposable systems, enhancements in electronic systems, and a focus on improving the patient experience.
Needle-free systems continue to be evaluated for specific applications; however, the predominant route of delivery remains a needle. Advances in needle technology, as well as the design of devices that minimize needle exposure before and after injection, help to reduce injection pain and phobia.
Another growth market for injectable- drug delivery is for devices that can help prevent accidental needlestick injuries. The Occupational Safety and Health Administration (OSHA) published guidelines to define desirable attributes for a safety device. OSHA recommends systems with safety features that are integral to the device, which includes safety features that are passive and require no intervention by the user, and a device that is safe and effective for patient care.
PharmTech : What are important technical considerations for prefilled syringes?
Reynolds: Development of improved packaging and delivery systems must take into account the needs of the pharmaceutical or biotechnology company as they relate to filling and manufacturing of the product. Novel systems should be compatible with established filling equipment wherever possible. Cleanliness and sterility validation are key. Contamination within the packaging can lead to costly rejects at the end of the filling process. Excessive silicone within the system can lead to aggregation with certain proteins or the formation of particles.
Breakage during manufacturing can also be a concern, particularly with hazardous or expensive materials. Breakage can occur during handling or upon assembly into a device. Broken glass causes manufacturing delays, safety concerns, costly overruns, and product returns. Users and healthcare professionals are vulnerable to the risk of shards and exposure to drug that can leak from the packaging.
The addition of needlestick prevention devices to a prefilled syringe may also be required. In the case of a staked or inserted needle, this feature can be in the form of a device that is assembled to the syringe after filling. For a luer-lock syringe, a safety needle can be added as part of a convenience kit.
In terms of materials, cyclic olefin polymers (COP) are an alternative to glass. These materials are as clear as glass but are lighter and less prone to breakage. They are resistant to water transmission, which is an advantage for maintaining a drug's shelf life. Used with a plunger coated with a fluoropolymer film, a COP syringe barrel is silicone free, which is an advantage compared with a glass syringe.