DELIVERY DEVICES - The New Industry Paradigm for Prefilled Success

INTRODUCTION

The prefilled syringe turns 40 next year. Since the filing of the first patents for a glass ready-to-fill syringe in 1974, this device class has attained an unrivaled position as the preferred choice for the delivery of parenteral drugs and vaccines. After a period of relative industry stability defined by peripheral innovation, a converging series of external and internal forces are set to reshape the prefilled syringe industry so that it will better serve the emerging needs of pharmaceutical companies, patients, and other stakeholders across the continuum of care.

More than 2 billion prefilled syringes are used worldwide each year. At least 60 drugs and vaccines are available in a prefilled format for use across more than a dozen therapeutic classes. These branded, generic, and biosimilar injectable therapies, collectively made by a who’s who of pharmaceutical companies, generate combined annual revenues in excess of $50 billion. Due to the continued success of these and other pipeline drugs, more than 3.6 billion prefilled syringes are expected to be used in 2015, with compound annual growth rates in excess of 10% for the foreseeable future.

The simplicity of the prefilled syringe has been the primary foundation for its success to date. It is both a sterile primary drug container and a drug delivery system. Composed of a glass barrel with rigid needle seal, an elastomer stopper, and a plunger, the prefilled syringe has very well understood materials in the drug fluid path and fits seamlessly into high-volume fillfinish systems. When compared to multidose vials, it eliminates overfill and significantly improves the time, convenience, and accuracy of delivering a dose to a patient.

The difficulty of administrating large molecules non-invasively has led to the progressive launch of a series of biotechnology drugs and vaccines, such as monoclonal antibodies, that are ideal for the subcutaneous or intramuscular injection of doses 1 mL or less in volume.

A MATURE, PROVEN DEVICE CLASS

The pharmaceutical industry now considers the prefilled syringe to be a mature device class that has a proven track record. To help streamline costs and standardize filling and packaging systems, the standard prefilled syringe has become largely commoditized under a one-size-fitsall model. Regardless of the supplier, the components that compose a standard prefilled syringe and the filling and packaging systems used during the fillfinish process are largely identical. Indeed, if you were to compare a standard 1-mL long prefilled syringe made today with one from the 1970s, they would be largely identical in design, functionality, and handling.

The handful of incumbent device and material suppliers active in the prefilled syringe market have also invested heavily behind a business model reliant upon the high-volume production of commoditized components. There are few device manufacturers who take responsibility for the entire package of components that comprise a prefilled syringe. As a result, pharmaceutical companies may source glass barrels from one supplier and elastomers from another. While this traditional system has helped to reduce costs and standardize fill-finish systems, it can complicate the supply chain and create the potential for quality control challenges should problems arise downstream.

Pharmaceutical companies with a longterm view are now displaying even greater concern about how the rigidity of this traditional model imposes restrictions upon them when they seek to leverage a prefilled syringe to optimize the delivery and commercial success of their injectable therapies.

A CHANGING LANDSCAPE

Where there has been prefilled innovation, it has largely been around the periphery. Examples include the development of elastomer coatings to enhance the suitability of prefilled syringes for use with complex biologics, or the attachment of secondary devices, such as ancillary safety products or auto-injectors. The industry has also made positive inroads towards improving component quality issues, such as glass breakage, and the removal of materials, such as tungsten from the fluid path.

Such superficial improvements to the prefilled syringe have been something of a stop-gap measure to address immediate customer, patient, regulatory, or safety compliance needs.

With pharmaceutical and healthcare markets having evolved so rapidly throughout the past decade, many leaders within the industry now consider that it’s time the prefilled syringe caught up with the injectable therapies they are designed to contain and deliver. Indeed, the 40th anniversary of the prefilled syringe may become something of a midlife crisis for those who remain entrenched in the status quo.

EMERGING MARKET NEEDS

Pharmaceutical companies now face a number of obstacles to their future growth that industry players within the prefilled syringe market should be closely aware of, and highly responsive to.

At the macro level, the healthcare system is responding to rising costs associated with the treatment of an aging population and the growing prevalence of chronic diseases by imposing pricing and reimbursement cuts, driving the uptake of generics, and increasing regulatory scrutiny on new drug filings. These changes are pressuring pharmaceutical companies to showcase how their injectable therapies generate value to patients, payers, and prescribers across the entire healthcare system.

Patients in particular are evolving, and in many ways, becoming more like consumers. In a world full of smartphones and tablets, they expect their injectable therapies to be convenient, portable, safe, and highly intuitive in use. Today’s patient generation is also highly brand-aware, and empowered to request that their physician prescribes the injectable therapy they believe is right for them.

Pharmaceutical companies are also acutely aware that the therapeutic markets in which they are active are becoming more crowded. Competition between brandname, generic, and biosimilar drugs will continue to heighten. In response, pharmaceutical companies are seeking to streamline marketing budgets and diversify their clinical pipelines with a range of targeted therapies that can help offset the anticipated loss of revenues from the expiration of their aging blockbusters.

With novel pipeline drugs costing at least $1 billion on average to commercialize according to most industry estimates, pharmaceutical companies recognize that they must fully leverage the critical position of the prefilled syringe as the primary interface between their drug and the patient. In a world increasingly defined by bioequivalence, it will be the drug that is most differentiated from its rivals and preferred for use by patients that will beat the competition.

In speaking with many pharmaceutical companies, it is apparent that five trends are now converging together to redefine not only the composition of a prefilled syringe, but the entire industry landscape. These five emerging or unmet market needs for the delivery of prefilled therapies are 1) Device Customization, 2) Lifecycle Management, 3) Needlestick Safety, 4) Brand Differentiation, and 5) Combination Therapies.

Device Customization

Injectable formulations are becoming more complex, quality assurance controls more stringent, and patient populations more targeted. The traditional model whereby manufacturers of glass barrels, elastomers, and associated materials have invested in the high-volume production of rigid commoditized prefilled syringes is rapidly becoming outdated.

Instead of pharmaceutical companies being asked to adjust their formulation or manufacturing processes to conform to a standard prefilled syringe, device manufacturers must look to provide in the future have greater flexibility in customizing their primary container materials and the overall user-functionality of the delivery system to address specific customer needs. This new industry paradigm will require long-term collaborations between drug, material, and device manufacturers that can begin earlier in the clinical development process and extend through the regulatory approval and lifecycle management of the combination product.

With only a handful of glass barrel and elastomer suppliers within the prefilled industry, pharmaceutical customers do not wish to be constrained to only the proprietary materials, lubricants, or coatings available from one company. Instead, many now desire an open architecture supply chain system in which they can select their preferred configuration of components, materials, and coatings that will comprise the perfect prefilled syringe. Device manufactures should have the breadth and flexibility in their supply chain network to support customers with a preference between one fluid path material or another.

Another key requirement for prefilled customization relates to the growing importance of human factors engineering. With prefilled therapies increasingly being targeted for self-administration by specific patient populations, the external design and functionality of the device must be tailored to specific user needs.

During the clinical development or lifecycle management of injectable therapies, drug and device companies must conduct user studies with the target patient group. Human factors that can be measured for patient acceptability include initiation force, glide force, and the activation force for a safety mechanism, the ergonomic design of finger flange, overall ease-of-use, and convenience of disposal. The data generated by these user studies can add significant value to the regulatory approval and commercial success of the combination product.

Lifecycle Management

The continuous enhancement of an injectable therapy throughout its commercial lifecycle is becoming a standard method of building market share and fighting off competition from current or prospective rivals. Traditionally, a pharmaceutical company would launch its therapy lyophilized in a vial, then transition a few years later into a liquid-stable format with a standard prefilled syringe, and then perhaps later add an auto-injector. The lifecycle management of Copaxone by Teva is an excellent example of lifecycle management in process. Today, however, the launch of an injectable therapy in a standard prefilled syringe is considered to be the absolute bare minimum required to compete.

With the standard prefilled syringe now widely acknowledged as a status-quo device, pharmaceutical companies are seeking access to best-in-class delivery systems that can improve therapy compliance and drive preference rates amongst patients and prescribers.

Potential may also exist for prefilled syringes to extend the commercial lifecycle of mature therapies. The conversion of a drug from a standard prefilled syringe into an enhanced, market-leading delivery system may allow the pharmaceutical company to retain some level of market share that would otherwise be lost to incoming generic or biosimilar rivals.

Furthermore, where there are proprietary primary container features within the prefilled syringe that can improve clinical outcomes, regulatory claims, or administration of a therapy, these advantages may potentially be utilized to obstruct the future entry of generic rivals that are unable to replicate these characteristics. Such device-related strategies may help a pharmaceutical company protect or regain significant revenue streams and operating margins during the mature years of a product’s commercial lifecycle.

Needlestick Safety

Europe and other international healthcare markets are now following the U.S. toward the mandatory use of devices with needlestick prevention features. These laws require the frontline staff of healthcare facilities to play a role in the evaluation, selection, and use of devices, including prefilled drugs that can eliminate or minimize the risk of occupational exposure to the lowest possible extent.

For pharmaceutical companies that must comply with these needlestick prevention laws, the selection of a prefilled syringe that can optimize levels of protection to healthcare workers can represent a significant competitive edge.

Traditionally, pharmaceutical companies have had two options for needlestick compliance. In the case of drugs and vaccines targeted for intramuscular injection, they can utilize a prefilled syringe in a needleless format. Such devices require healthcare workers to attach a safety mechanism, such as a needle guard onto the prefilled syringe, immediately before injection. However, data suggests that such manual safety products are frequently not activated by the healthcare worker, or associated with needlestick injuries either during use or after disposal.

A more common approach has been to attach an ancillary safety product onto the prefilled syringe after it has been filled with the drug and prior to packaging. The process of attaching an ancillary safety product can require the purchase, installation, and operation of additional assembly systems within the pharmaceutical cleanroom. Any problems associated with the breakdown of these assembly systems or the subsequent breakage of the prefilled syringe can impact the financial efficiency of the entire fill-finish process. The bulky size of these ancillary safety products compared to a standard prefilled syringe also increases packaging, transport, and storage volumes by up to 60% to 70%.

OSHA, the FDA, and many healthcare associations cite a preference amongst healthcare workers for the selection and use of devices with automatic (passive) and integrated safety features that can minimize the risk of harm and best comply with routine injection procedures. Pharmaceutical companies that select such prefilled devices with automatic, integrated safety features will be in a strong position to leverage these protective and functionality benefits to build user preference rates and optimize market share.

Brand Differentiation

Devices that are differentiated and offer true benefits to the patient can be leveraged by pharmaceutical companies to optimize the commercial value of their injectable therapies. The insulin market is a perfect example of how the patient delivery system can be just as important as the drug itself when it comes to driving patient preference and building market share. However, when one standard prefilled syringe product looks much like any other, options to differentiate an injectable therapy from rivals can become extremely limited.

The challenge extends to ancillary products that are attached onto the standard prefilled syringe, such as ancillary safety products and disposable auto-injectors. In both these cases, the functionality and external shape of these bolt-on products are similar across available brands marketed by relevant manufacturers.

An elegant, sleek, and attractive device that is devoid of unsightly springs, compact in size, and has an external form factor that can be customized to specific drug brand or patient needs can generate powerful levels of differentiation. User opportunities for differentiation may include a more intuitive device that offers fewer steps of use, an unobstructed view of the drug, or the use of audible, tactile, and visual indicators to signal delivery of the full dose. Pharmaceutical companies that are able to access prefilled devices that can be customized to address the specific therapy needs and create the safest, simplest possible injection experience for the patient will have the best opportunities to generate powerful brand differentiation within competitive markets.

Combination Therapies

Prefilled syringes have traditionally been limited to the containment and delivery of liquid stable drugs and vaccines available in a single measured dose. Standard prefilled syringes are therefore unable to accommodate the needs of therapies that require reconstitution or mixing at the point of delivery.

Around a third of novel injectable drugs and vaccines launched in the U.S. during recent years have been in a lyophilized format, either because they cannot be made liquid stable or to fast-track time to market. Traditional reconstitution systems can require a dozen or more steps of use, and are largely unsuited for selfinjection by patients. A new generation of injectable therapies supplied in a liquidliquid combination for mixing at the point of use will also be launched onto a number of healthcare markets this decade.

Prefilled syringes with dual or multichamber configurations that can efficiently contain a combination of liquid or dry drug combinations in a system that is ready for efficient reconstitution or mixing at the point of delivery have significant potential to transform the treatment of countless chronic or acute conditions. Only a few such dual-chamber prefilled syringes are now available to pharmaceutical companies.

FUTURE OUTLOOK

A number of internal and external forces have led the prefilled syringe industry to a state where it is primed for change. In the future, the prefilled syringe is set to transition from being an off-theshelf commodity device, to one in which component materials, functionality, and branding are fully customizable.

To succeed in this new environment, device manufacturers must follow a new paradigm for market success. They must be committed to serving pharmaceutical companies under long-term partnerships throughout the clinical development and commercial lifecycle of the drug-device combination. They must have the right balance between operational capabilities and business agility to ensure they are responsive and adaptable to emerging customer needs. They must have quality standards that exceed the industry benchmark and instill confidence and reliability into the pharmaceutical supply chain.

Device manufacturers must also possess management depth with strong levels of technical expertise so that their knowledge base can rival, and in some cases exceed, those of pharmaceutical companies. They must have a broad portfolio of flexible, differentiated device technologies that are platform-based instead of being rigid products. And they must be fully committed to working with their customers to enhance or enable the commercial success of their injectable therapies. Unilife is one such company that is ready to serve these emerging, unmet needs of customers seeking to enable and enhance their injectable therapies.

Alan Shortall is the CEO and Founder of Unilife Corporation, a US-based company engaged in the design, development, production, and supply of injectable drug delivery systems. Unilife builds long-term collaborations with pharmaceutical and biotechnology companies seeking to utilize its innovative and highly differentiated devices to enable or enhance the clinical development, regulatory approval, and lifecycle management of their injectable therapies. Unilife has developed a broad range of highly innovative single and multichamber syringes that meet the needs of all drugs, vaccines, and biologics and are strongly accepted and preferred by users. In addition to prefilled syringes with USP compliant materials and integrated, automatic safety features, pharmaceutical companies can select from a broad portfolio of proprietary device technologies, including reusable and disposable auto-injectors, bolus injection devices, and targeted delivery systems. Each of these device platforms can be customized to address specific customer, drug, and patient requirements.