Patient-Administered Therapies Drive New Delivery System Designs

Historically, one of the barriers for patient acceptance of injectable drugs is a simple but practically unavoidable one: fear of needles. Today, however, the increasing shift from inpatient hospital care to outpatient services and home care is driving innovation in self-administered drug-delivery systems.

Even after overcoming patient fears, additional obstacles are ensuring safe, accurate drug administration, and meeting the needs of such patients as those suffering from rheumatoid arthritis, which can make manipulating a syringe difficult. All these concerns collectively are driving increased innovation in syringe designs, added safety and dosage features, and protection against contamination from syringe components. The fact that many of the newest, high-value biotech products are injectables only adds further incentives for manufacturers to design syringes and injectors more carefully.

“Injection devices are rapidly becoming an important strategy in the life-cycle management of diseases to treat chronic conditions, whether it is migraine or rheumatoid arthritis (RA),” notes Sheila Dell, PhD, a VP at Catalent Pharma Solutions (Somerset, NJ). “The increase in the aging population will affect the rising demand for these treatments going forward as well.”

Proper injectable practices are a challenge for healthcare providers themselves, let alone patients self-administering drugs. This is evidenced by the launch of the Safe Injection Practices Coalition (oneandonlyca mpaign.org) to raise awareness that syringes and other administration devices should be used only once to prevent cross-contamination. The Coalition brings together several provider professional groups, CDC and FDA, and manufacturers including Becton Dickinson, Hospira and Covidien. The One & Only Campaign is aimed at promoting safe injection practices across healthcare settings to protect all patients. A study by Premier Inc., the Charlotte, NC, GPO, showed that 6% of providers sometimes use the same vial to administer injectables to multiple patients; and that 1% sometimes reuse syringes (thinking that merely replacing the needle is sufficient to prevent infection). Premier, also a Coalition member, published the study in the December issue of the Am. J. of Infection Control.

 

 

SCHREINER MEDIPHARM'S NEEDLE COVER PREVENTS ACCIDENTAL STICKS

According to published reports, a lack of understanding exists about current
regulations and guidelines governing basic safe injection practices and infection control protocols. This is despite the fact that FDA mandates Rx drug labels containing information for administration. “There are usually fairly explicit details with pictures about how to inject,” notes Karen Mahoney, an FDA spokesperson. “FDA evaluates labels and labeling prior to marketing for their potential for medication errors.”

The frequency of patient-administered therapies is being driven, in part, by increased incidence of diabetes and chronic diseases like multiple sclerosis (MS) and RA, plus an increasing number of new biotech-based therapies and vaccines. Many injectable therapies require regular injections, often performed by the patient or caregiver in the home, which can be difficult.

Ease of use is therefore of increasing importance, which means that the preferred application form are PFS (prefillable syringes),” says Claudia Petersen, director of business development at Gerresheimer Bünde (Düsseldorf, Germany). “This is one of the reasons why the PFS market still shows a sound growth rate.” Gerresheimer is a manufacturer of high-quality specialty products made of glass and plastic for the global pharma and healthcare industry.

Safety and convenience
Prefillable syringes are projected to post the fastest market growth among all primary parenteral packaging based on infection prevention and response time advantages in the delivery of emergency and critical care medication, according to the Freedonia Group (Cleveland), a market researcher. Many of the latest delivery systems and accessories are touted as being safer to use because they help prevent needle-stick injuries.

For example, the Gerresheimer TELC from features a Luer Lock closure which combines the standard function of a conventional Luer Lock syringe plus tip cap with an additional tamper-evident function. Unilife Medical Solutions offers a ready-to-fill syringe featuring a retraction mechanism integrated into its barrel component. After drug delivery, the mechanism activates automatically and retracts the needle into the barrel.

SYRINGE CONFIGURATIONS FROM CATALENT

Catalent has forged strategic partnerships with companies such as Innovate, a move which led to the development of the Protector Safety Shield System. This provides a platform of technologies designed for needle stick protection, Dell says. “Catalent can combine these safety devices with its complete line of prefilled syringes, providing patients with improved safety and enhanced product performance.”

Another example comes from Schreiner MediPharm (Blauvelt, NY), which has been marketing the Needle-Trap system for the past two years. Needle-Trap combines a multi-function label (label conversion being Schreiner’s main business) with a plastic cap-type component that allows needles, once used, to be enclosed, thus preventing needle sticks. More recently, the company introduced a multi-function label for auto-injectors that combines patient information with tamper evidence.

In addition to safety, advances are being made in providing more user-friendly delivery systems, industry watchers say. In developing Cimzia, the only approved PEGylated anti-TNF, UCB (Brussels) reports it set out to design a prefilled syringe that would be easy for people with RA to hold and comfortable for them to use. Designed by the biopharma company in partnership with OXO Good Grips and created with input from people living with RA, Cimzia enables someone with RA to use and control the syringe with either one or two hands, depending on grip strength and control.

Freedonia Group reports one of the most popular devices for self-administering insulin and other injectable medication with frequent dosing requirements is pen injectors. Innovations in prefilled insulin pen injectors have led to the commercialization of new automated dosing devices that provide for greater drug administration accuracy. One such device on the market is Novo Nordisk’s (Denmark) Innolet, a hand-held configuration featuring an oversized dial attached to a cylinder-shaped barrel that contains a prefilled cartridge of insulin. The needle tip is placed on the skin and a large activator button on the top of the device is pressured to administer the insulin.

Eli Lilly (Indianapolis) offers four different insulin formulations in its prefilled pen injectors: Humalog, Humalog Mix 75/25, Humulin, and Humulin 70/30. The dosage dial moves backward and forward, allowing for the easy correction of entry errors. A magnifying window built into the pen’s body enables the user to confirm the number of insulin units prior to injection.

While pen injectors and multi-dose cartridges can be used for those who have frequent needs, these systems are limited to specific therapies such as diabetes and growth hormones, which often require weighed dosages or dose titration. “They are not ideal for chronic users of fixed-dose medications,” notes Graham Reynolds, a VP at West Pharmaceutical Services (Cincinnati). “Easy-to-use auto-injector systems, which are based on prefillable syringes, are a more convenient method for delivering drug products, especially for patients who may have dexterity or needle phobia issues.”

West, a manufacturer of components and systems for injectable drug delivery, offers the ConfiDose auto-injector system which allows the patient to have full visibility of the drug content while a single push-button activation enables automatic insertion, delivery and retraction of the needle. “The three-step operation has audible, tactile and visual indicators that function to assure the patient that the full dose has been given,” Reynolds explains. “A hidden needle is fully protected before and after injection, which make the system safe to use and easy to handle.”

Biotech Drugs Influence Use of Packaging Materials
The conversion of vials to prefilled syringes in various therapeutic categories, most notably vaccines and biotech drugs, is considered one of the most prominent changes in parenteral drug packaging in the past decade. But changing the primary packaging for a parenteral is typically a challenging project, industry members say, with extensive commitments both in terms of people and capital. Pre-filled, single-dose syringes 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.

What’s more, new, sensitive biopharmaceuticals are forcing the industry to deal with packaging and delivery systems much earlier in the process. “Protein therapeutics are partly much more sensitive regarding potential interactions with leachables from the syringe system compared to chemical entities,” Gerresheimer’s Petersen says. “Syringe suppliers are addressing this problem by continuously improving their processes to minimize/eliminate the leachable source and increase product quality also with regard to cosmetic and dimensional aspects.”

Suppliers say they are making progress in addressing these areas. For instance, Schott offers a syringe specifically designed for sensitive biotech drugs that makes injections less painful for patients. The InJentle syringe employs a “pinch seal” closure which ensures the drug is not in contact with the metal needle or adhesive of the syringe during storage, preventing contamination. The novel system was developed by Schott’s Pharmaceutical Packaging division in Switzerland with input from Cambridge Consultants (Cambridge, MA).

SAFETY SYRINGE'S ULTRASAFE DESIGN INCORPORATES SCHOTT'S 'INJENTLE' TECHNOLOGY

“The InJentle syringe has a built-in ‘valve’ system between the barrel and needle to avoid leachables such as tungsten,” explains Alexander Jaksch, director of business development and marketing, Safety Syringes (Carlsbad, CA). The company markets UltraSafe Needle Guards for prefilled pharmaceutical glass syringes used for vaccines, low molecular weight heparins, and other medicines.

Most prefillable syringes are based on glass, which may cause safety issues such as breakage and delamination. Newer drugs, including those with high viscosity or the need to be administered in high volume, have the potential to interact in a negative fashion with glass containers. “For instance, in a vial format, glass delamination is a potential issue,” West’s Reynolds says. “In staked-needle syringe systems, there are considerations such as adhesives, tungsten and silicone oil that can cause interactions.”

The consideration of alternative packaging materials, although typically priced higher than glass, mitigates many of these issues and allows for more rapid development. The availability of cost-effective pre-fillable plastic syringes based on high-barrier COC resins provide the strong chemical resistance and high clarity needed for packaging parenteral drugs. It also enables companies to create easy-to-use, safe devices and systems without having to conform to the traditional container closure systems, such as vials or prefillable syringes, experts say.

Biopharmaceutical and pharmaceutical companies, with the help of delivery systems companies such as West, are introducing break-resistant COCs for pre-fillable syringes, such as Daikyo Crystal Zenith, and unique designs that allow for easier and safer injection. “These systems are not only manufactured from a novel plastic material that reduces the risks of breakage,” Reynolds explains, “but the dimensional tolerances, quality standards, and freedom from materials such as silicone oil, tungsten or adhesives ensure that the systems provide the combined benefits of a plastic with the features necessary to contain a sensitive biopharmaceutical.”

As the industry moves toward being more patient-centric, experts say product development will enable pharma companies to produce unique, safe and easy-to-use devices or delivery systems. Working closely with a knowledgeable manufacturer can help any company create a delivery system that provides excellent containment, safe administration and full-dosage delivery while mitigating risk.