2009 saw a rise in biological drug product approvals, which demonstrates significant promise and growth potential for treatment of previously refractory diseases. This development is expected to stimulate further innovation in parenteral delivery systems, experts say, as new protein-based therapies are administered through injection or infusion.
“The growth of the biologics portfolio is helping drive the need for parenteral dosage forms,” observes Holly Bonsignore, director of Pfizer’s (Madison, NJ) new products group. “Also, there is a drive for increased innovation in delivery systems, or routes of administration to maximize the value of our products.”
New drug delivery technologies are also driving the shift from inpatient hospital care to outpatient services and home care, industry members say. As a result, recovery and chronic conditions are increasingly being managed at home, many requiring the delivery of complex drug regimens. “There is definitely a trend towards prefillable syringe systems and other, easy-to-use self-administration delivery systems that can be used in either the home or clinical setting,” said Graham Reynolds, VP, marketing at West (Lionville, PA).
Syringes and vials, still the workhorse delivery technology for injectables, are expected to continue to lead unit demand among parenterals, as a large percentage of existing and forthcoming injectable drugs are produced in lyophilized or dry powder formulations not easily adaptable to syringe packaging, according to the Freedonia Group, a Cleveland-based market researcher. While vials remain a cost effective packaging option to pharma companies, as drugs become generic, these delivery vehicles offer little opportunity for differentiation. “Therefore, vials are probably best suited to the early stage of the product lifecycle from the drug company’s perspective, before moving into pre-filled and then into more highly differentiated device packs,” says Phil Lever, head of drug delivery at Cambridge Consultants (Cambridge, MA), a design and development firm.
By comparison, prefillable syringes are projected to command the strongest growth in this product segment, Freedonia says. Offering infection prevention and response time advantages over alternative hypodermic systems, world demand for these devices (excluding the cost of medication) will expand nearly 9% annually to $1.6 billion in 2011, the market researcher projects, with prefilled cartridges adaptable to reusable injectors accounting for most unit consumption.
Cost disadvantages versus vial and ampul packaging are expected to moderate overall growth opportunities for prefillable syringes by keeping most applications confined to critical care, emergency and highly contaminant-vulnerable medication. “The trend over the last 15 years has been to produce single-use doses in prefilled syringes when the drug is often used in emergency room or field situations,” observes Crystal Rice, a spokesperson for FDA. “The convenience of prefilled syringes for self-administered products is one probable driver of this change.”
Drugs with a more convenient system for preparing and administering the doses often determine patient acceptance, experts say, with physicians prescribing dosage forms with proven patient satisfaction and compliance. “In parallel, pharmaceutical companies are using device technologies as a means for building product differentiation and brand/patient loyalty,” Lever contends. “This, in turn, is giving rise to a proliferation in ‘smarter’ parenteral devices, especially in the self-administration area, to service the growing market of ‘medical consumers.’”
The injectables market witnessed rapid growth the past five years, attributed largely to increased incidence of diabetes and autoimmune diseases, including MS and rheumatoid arthritis, plus an increasing number of new biotech-based vaccines. As biotechnology grows in importance, the science and engineering of primary packaging for injectable biopharmaceuticals is taking on new prominence, experts say. Biotech products have had a number of issues because these protein products tend are sensitive to leachates and preservatives that can lead to product-related variants and potential changes in the immunogenicity profile.
“Most biotech drugs are very sensitive and the step of lyophilization (in vials) has to be done to guarantee the stability and safety of the drug,” says Christa Fritschi, marketing director, Schott Pharmaceutical Packaging (Tarrytown, NY). “Single-dose syringes are utilized where a stable liquid formulation is feasible and a self-administration therapy is targeted.”
Prefilled, single-dose syringes also face a number of challenges, such as compatibility with syringe components due to prolonged contact with the drug, as well as sterility assurance from pressure differential during air shipping. Contamination and exposure are important considerations for drugs which require reconstitution, experts point out, and where the drug is either sensitive to contamination or presents a risk from exposure to patients or clinicians. Suppliers say they are making progress in addressing these areas, and offer a number of new solutions which improve the reconstitution process.
For example, West’s MixJect adapter is positioned as a convenient solution for reconstituting a drug with a diluent prefilled syringe; upon reconstitution, the drug is available for immediate injection with a dry pre-attached needle. In January, Schott launched a new kind of syringe that as well as being specifically designed for sensitive biotech drugs, makes injections less painful for patients. The new InJentle syringe, launched in January, employs a “pinch seal” closure, ensuring the drug is not in contact with the metal needle or the adhesive of the syringe during storage, preventing potential contamination.
The novel system was developed by Schott’s Pharmaceutical Packaging division in Switzerland with input from Cambridge Consultants. “The Schott InJentle is a new and innovative staked-needle syringe which is tungsten-free, has no leachables from adhesives, or contact between drug and needle,” Fritschi says. “It has a tamper-evident closure and offers gentle application, a thin needle and easy handling.”
The most cost-effective prefilled syringes are needled and blunt-point cartridges adaptable to reusable injector devices. According to Freedonia, these containers are deployed widely in the delivery of insulin as well as anticoagulants, antibiotics and pain control agents. ”The need for prefilled syringes is determined by the disease area, frequency of administration, by whom and where the product is administered, balanced by the value of a prefilled syringe to the patient and caregiver,” explains Rich Hollander, senior director of packaging services for Pfizer’s Global Manufacturing group.
Some of the latest prefilled syringes offer a leap forward in convenience for the user, industry watchers say. For instance, growth of disposable injections is being driven, in part, by complexity of design and use in the delivery of more sophisticated meds. Devices such as insulin pens—where pre-filled syringes/cartridges are used—enable users to dispense a dose on demand.
The increased demand for drug delivery devices intended for self administration in a non-clinical setting has resulted in the development of a new class of self-injection products for drugs that require reconstitution.
Last fall, West teamed up with a design firm, Insight Product Development (Chicago), to offer Confidose, a disposable auto-injector system for self-injection therapy. Confidose incorporates an affixed needle prefilled syringe format that can be used with either a glass or crystalline plastic syringe.
Observers say the self-administration market is also seeing increased use of electronics in devices to boost patient compliance, comfort and acceptability. A case in point is Easypod, the newest addition to Merck Serono’s family of growth hormone (GH) delivery vehicles. According to the company, Easypod combines all the benefits of autoinjection with intelligent electronics that enable patients to carry out their daily GH treatment in three steps.
With unique features such as preset dosing, assisted needle attachment and dose confirmation, Easypod is said to make daily injections easy while assuring meds are injected correctly. “The opportunity for a smart device that can communicate with clinicians and healthcare providers remotely via the Internet (connected health) is also an area of significant future interest,” Cambridge Consultants’ Lever says. “We also see a trend to more feature-rich devices with a greater focus on human factors, and ergonomic designs targeted at specific therapeutic areas and patient groups such as geriatrics, pediatrics, and the vision- or dexterity-impaired.”
All materials for parenteral packaging—including glass, the dominant material—are being scrutinized more closely as new types of proteins and peptides, with unique chemical, physical and mechanical properties, enter the market, industry members say. Historically, the high cost and complexity of meeting regulatory requirements discouraged producers of parenteral drugs from switching to plastic containers in most existing applications. But some newer and more sensitive drugs have problems with glass, industry members say, as they may leave a portion of the drug behind in vials, which factors into filling costs.
“This renders glass as a fairly limited material when device engineers are seeking to introduce new geometries and device formats that are feature rich and compact in design,” Lever says. “For example, the scope for fundamental change in the design of auto injector technologies is significantly impacted by the geometry and characteristics of the prefilled syringe they are often constructed around.”
Plastic is making its presence felt in prefilled syringe injectors, an area where packaging costs are typically 25% more than packaging the same medication in vials or ampuls, Freedonia says. The availability of cost-effective prefillable plastic syringes, such as Baxter’s Clearshot, Becton Dickinson’s Sterifill SCF, and Schott’s Toppac, is reportedly changing this trend. All are based on high-barrier COC resins that provide the strong chemical resistance and high clarity needed for the packaging of parenteral drugs.
In the primary packaging area, cyclic olefin copolymer (COC) and cyclic olefin polymers (COP) are some notable examples of glass alternatives being used in certain applications, such as emergency medicine. Topas Advanced Polymers (Florence, KY), a producer and marketer of engineering polymers, is making a push to establish COC as a material of choice for prefilled syringes and vials. The firm claims Topas COC is ideal for medical packaging because it offers a combination of clarity, moisture barrier, high purity and inertness.
“Topas COC preserves drug quality because it has very low leachables and extractables that do not interact with drugs to alter drug purity or potency levels,” declares Barbara Canale, market development, medical applications. “Topas resin is a biologically inert polymer for drug packaging compared to medical glass.” Topas COC works well with biomass delivery products as well for bone replacement surgery.
West offers a COP under the brand name Daikyo Crystal Zenith (CZ). The polymer, a product of West affiliate Daikyo Seiko (Tokyo), is said to be the first silicone-oil-free material on the market and offered for both prefillable syringe systems and vial construction. The main advantage of this product is it does neither need fluoropolymer lamination nor silicone lubricants for plunger movement.
“One of the reasons customers choose the CZ resin syringe system is because it offers much less variability in functionality than traditional glass systems,” says Fran DeGrazio, VP, marketing and strategic business development. “Coupled with a plunger with West FluroTec barrier film, the CZ resin syringe system does not require siliconization, which leads to variability and can affect the gliding performance of the plunger.”
Novel materials such as the CZ resin give customers the benefits of low extractables, break resistance and high quality in a vial or syringe system. The CZ resin can be molded into complex shapes, an advantage over glass. “Pharmaceutical companies can select a CZ containment solution for the life-cycle of their drug,” Reynolds said. “This means that as they move their drug product from development to clinical trials to commercialization, they can use a containment system manufactured from the same material, an important consideration because the material’s performance characteristics are consistent.”
As highly cost-competitive materials such as COP and COC gain traction, experts say the challenge is to get widespread adoption through clinical and regulatory acceptance. “Once this occurs,” Cambridge Consulting’s Lever says, “it is likely that prefilled parenteral-delivery devices will change significantly in form and function as more complex and compact geometries will be achievable through low-cost molding techniques.” PC