Graham Reynolds, West Pharmaceutical Services, Inc.

	For a newly diagnosed patient suffering from chronic conditions, such as diabetes or autoimmune diseases, the thought of a daily injection can be frightening. Failure to use a delivery device or system, such as an insulin pen or auto-injector, correctly could result in a life or death emergency, or impact their ability to manage their condition effectively. For the pharmaceutical manufacturer, such a failure could result in a massive backlash that may cause loss of market share, costly product recalls or worse.

Fig. 1. An integrated system combines the

				requirements of the drug itself with patient human

				factors, the delivery device and the primary

	The primary goal of any drug delivery system is to ensure that a patient receives a proper dose of a prescribed drug. In years past, if a device failed or was used incorrectly, patient error was most often the culprit. While providing detailed instructions is important for any pharmaceutical manufacturer, failure to follow directions is no longer a viable excuse when a patient or caregiver is unable to operate a device or delivery system successfully.

	Effective drug therapy and treatment requires more than simply having an effective molecule. Rather, it is the combination of a safe drug within a suitable container and/or delivery system, as well as an understanding of patient needs as it relates to adherence. By working closely with a packaging and delivery system manufacturer that has generated partnerships with companies like assembly equipment manufacturers, filling companies, human factors experts and design companies, pharmaceutical manufacturers can develop an appropriate integrated containment and delivery system that maximizes the chances of moving a product to market quickly and effectively.

	Historically, pharmaceutical manufacturers have focused—and rightly so&mdash;on the efficacy and safety of the drug product. However, if the drug is to achieve its therapeutic objective, then its primary container and delivery system must be both compatible with the drug and stable over time, as well as foster adherence from the patient. A drug can only truly have the desired patient benefit if it is taken as prescribed, delivered effectively (often by a patient or caregiver), and maintains performance over time.

	Many years ago, a pharmaceutical manufacturer needed only to make a drug available for use with a vial and syringe. As needs evolved, so too did delivery techniques. Patients who required daily dosing or those with special considerations, such as hemophiliacs, needed new ways to mix and inject drugs that lowered the risk of needle stick injuries, and increased adherence to therapeutic regimens. Mixing and transfer devices helped create a needle-free preparation environment for hemophiliacs. For chronic users of fixed-dose medications, including diabetics, injection systems such as pen injectors, pumps and multidose cartridges helped to ease the burden of regular dosing.

	Today’s injectable therapies can take many forms. Liquid drugs may use a traditional syringe and vial; a prefilled syringe; or a delivery system such as an auto-injector, pen device or patch injector. Lyophilized drug products (requiring reconstitution with water for injection) may require a kit containing a transfer device, syringe or needle, and containers of the drug and water. As the trend toward self-care continues, and patients take an even greater role in decisions regarding their treatment, easy-to-use delivery systems will be essential. Increasingly, the market is evolving toward the use of sophisticated, patient-friendly delivery systems suitable for the home environment. Since there is a strong correlation between the ease of drug product administration and patient adherence, manufacturers must shift from a product-centric to a patient-centric focus when designing a drug delivery system. Such a move can help to differentiate the product in the market, while fostering patient adherence and encouraging brand loyalty.

	So how does a pharmaceutical manufacturer deliver a system that meets compliance requirements and the needs of both the drug and the patient, while offering differentiation to their product in a crowded market? First, consider the interface between the drug and the container itself. Selection of a material that can be used during the drug discovery phase and travel through to a self-injection platform is an ideal solution for containment. Effective containment should maintain stability, efficacy and quality over time, while meeting appropriate regulatory and quality standards. Novel materials, such as moldable cyclic olefin polymers, can help pharmaceutical companies manage a drug throughout its life cycle because the material can be used for bulk storage during development, and primary containment when ready to move to market.

Fig. 2. West’s SmartDose delivery system

				employs a patch for repeatable injection of

	The container format itself also should be considered. Vials may be necessary for initial use, but a syringe or cartridge system may provide the best solution for the patient when the system reaches the market. Custom systems may also help to differentiate the product, and should be considered early in the development process.

	Once the primary container has been selected, efforts must be made to ensure that it works with the delivery system. Dimensional tolerances and functionality should be tested to ensure proper activation and gliding forces.

	Recognizing how the patient interacts with the delivery system is essential to ensuring success in the market. Even the most innovative drug can provide the appropriate therapeutic benefit to the patient only if it can be delivered effectively and the patient adheres to the necessary treatment regimen. Patients may choose one product over another based on dose frequency, pain associated with dosing, or ease of use or mobility of the delivery system. Simply put, packaging can differentiate a product’s market acceptance. An excellent example of a drug product offering that is designed to suit patient preference is Merck Serono’s Rebif. Rebif (interferon beta-1a) is used to treat relapsing forms of multiple sclerosis, and is available in a range of patient options, all designed to improve the patient experience, including prefilled syringes and self-injection systems.

					Just as the technical options for containing a self-injected parenteral are evolving, so are the choices for the label that surrounds that container. Schreiner MediPharm (Blauvelt, NY), for one, is

					carving out a niche for what could be called “functional” labels that go beyond simply identifying the product. The widening range of options include:

					• Temperature indicator, using an ink that reversibly shifts color when a defined temperature (for storage

					• Reminder features, making use of label parts that can be personalized for the patient’s individual data.

					Detachable layers can provide a notation that can be kept in patient records.

					• Anti-slip varnish/tactile elements, which allow for an improved grip of the pen, and to differentiate one pen from another containing a different medication.

					• Medication check/UV protection, for pens with a transparent window to check the contents.

					• Integrated tamper and counterfeit protection—usable both overtly (visually) and covertly (requiring an electronic reader).

					“Patients who regularly perform selfinjections will welcome the assistance provided by our new customizable label,” says Gene Dul, president of Schreiner MediPharm US.

	To make a truly effective product, the patient must be at the forefront of the delivery system design. Any potential failures of use must be predicted and designed out. Human factors testing allows manufacturers to support delivery system development from a range of critical perspectives. From a regulatory standpoint, such testing accounts for important human factors inputs that regulatory agencies expect to see as part of the development process for any delivery system. These same inputs also ensure that risks from user-based errors are identified early in the development process, and provide critical user information to the development team for risk mitigation measures. The full development process should consider the effectiveness of the integrated delivery system constantly, and risks should be mitigated.

	The process by which a testing team engages users should also yield valuable information regarding a user’s physical and emotional needs, desires, and the lifestyle challenges faced in managing the disease.  This information is a foundation for guiding the design process to develop delivery systems that are not only intuitive and easy to use, but also encourage experiences that enable positive emotional connections between the user and delivery system.

	Patch injection systems that are tailored to the needs of the end user provide an excellent example of the balance between an effective drug containment system and a user-friendly delivery system. In spite of internal system complexity, patch injector systems can be designed for simplicity and patient comfort, while facilitating the delivery of innovative drug products.

	Other options include designs that center on more traditional containers, such as vials or prefillable syringes. Auto-injectors have long been recognized as a convenient method for delivering drug products, especially for patients who may have dexterity or needle-phobia issues. Auto-injector designs can be combined with prefillable syringe systems made from cyclic olefin polymers to help prevent breakage.

	New designs are evolving around the needs of today’s growing pharmaceutical and biopharmaceutical markets. Many of these technologies may increase the price of the drug product, and pharmaceutical companies are challenged to justify those additional costs, particularly in reference to the delivery system or device. Integrated systems that encourage ease of use may aid in increased sales, higher revenues, customer loyalty and retention of market share. However, to truly justify the cost, it may help to go further back in the manufacturing process.

	As previously mentioned, material selection can make a difference in the quality of the product. Moldable cyclic olefin polymers can be used throughout a drug product’s life cycle, which can diminish the many rounds of testing required to ensure that the drug product is stable in different containment systems. Other quality issues, such as rejection rates and breakage, can be mitigated through the use of high-quality polymers. Often, the extra cost associated with these materials can be justified through quality improvement and increased sales, as well as a faster move to market.

	Whether seeking to create a custom integrated delivery solution or to package a drug product in an existing delivery option, such as an auto-injector, manufacturers should seek out a partner with expertise and experience in providing packaging solutions. Packaging manufacturers who are focused on providing quality solutions will have the knowledge and partnerships in place to ensure that all elements of an integrated design are met. New and innovative drug delivery systems can optimize the quality of life for patients by effectively managing the interrelationship of the four primary components: the drug, the end user, the primary container and the delivery system. Together, packaging and pharmaceutical manufacturers can work seamlessly as partners to provide innovative solutions that help mitigate risk, encourage patient adherence, and enhance value through integrated delivery combinations.

Graham Reynolds is Vice President, Marketing & Innovation, West Pharmaceutical Services, Inc. (

), where he leads initiatives to market novel delivery systems and develop strategies for future growth, including the acquisition and development of new technologies to enhance West’s portfolio. Graham holds a degree in Polymer Technology from Trowbridge College, UK.

, including West’s SmartDose electronic patch injector system technology platform,* are being developed to aid patients with self-administration. The SmartDose system, which features a Daikyo Crystal Zenith cartridge designed specifically to hold high-volume doses of sensitive biologics, offers a subcutaneous, programmable electronic injection system that adheres to the skin, and can deliver the drug over time. User interfaces optimized through human factors studies, including electronic indicators, can aid in patient adherence and caregiver monitoring. The SmartDose technology can be tailored to a specific patient’s needs, and is an excellent example of the balance between an effective drug containment system and a user-friendly delivery system. In spite of the internal system complexity, SmartDose has been designed for simplicity and patient comfort, while facilitating the delivery of innovative drug products.

					Auto-injector systems, such as West’s ConfiDose auto-injector technology platform* can be combined with the Daikyo Crystal Zenith 1mL insert needle syringe to help prevent breakage and other issues associated with glass prefillable syringes. The ConfiDose auto-injector system is designed to minimize the force an auto-injector places on a syringe system’s weakest areas, so the system can overcome many of the issues that may occur when glass systems are combined with viscous products. In addition, the insert needle syringe has the potential to contain a higher volume of drug than a conventional 1mL long glass syringe.

*For investigational use only by our pharmaceutical and biotechnology development partners.

					West markets the SmartDose and ConfiDose as integrated systems with drug filling and final assembly completed by the pharmaceutical customer. Daikyo Crystal Zenith® is a registered trademark of Daikyo Seiko, Ltd. Daikyo Crystal Zenith technology is licensed from Daikyo Seiko, Ltd. ConfiDose® is a registered trademark of West Pharmaceutical Services, Inc., in the United States and other jurisdictions. SmartDose® is a registered trademark of Medimop Medical Projects, Ltd., a West company.

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Design choices can make a difference in a crowded market