Bolus Injectors: Medication Adherence, Safety, and Convenience

By Michael D. Hooven

There are approximately 900 biologic drugs in development today. But despite their promise for advancing treatment of cancer, immunologic disorders, rare and chronic diseases, the full benefit of biologic and immunologic therapies will only be realized if patients adhere to their medication regimen (Goldberg et al., 2009). To promote patient compliance, improve safety, and reduce costs, a new method of administration is being developed: bolus injectors.

The medical literature leaves little doubt that taking medication as prescribed and for the recommended time period is problematic for many patients and can significantly impact healthcare outcomes and cost of care (Dunbar-Jacob & Mortimer-Stephens, 2001). A World Health Organization (WHO, 2003) report cites non-adherence as a leading cause of preventable morbidity, mortality, and cost. Yet compliance among chronic disease patients averages just 50%.

By 2016, biologics are expected to account for 50% of the top-100 selling drugs. But a large number of these large-dose and often viscous formulations cannot be injected with today’s syringes, pens, or other legacy systems. They must either be delivered intravenously or by a new drug delivery technology that is in development for safe, patient-friendly self-administration.

Automated Bolus Injectors

	Figure 1. Bolus Injector Prototype – Patient inserts the vial into the injector, adheres it to his or her body, and pushes one button.

The WHO report cites complexity as one of the six major causes of failure to comply with prescribed medication. Reducing complexity and its associated cost is one of the biggest challenges facing the pharmaceutical and biotech companies developing the biologic drugs, monoclonal antibodies, and immunoglobulins that may soon revolutionize treatment of cancer and chronic diseases.

Bolus injectors, an new class of drug delivery devices for subcutaneous self-administration of biologics, address these challenges of complexity and patient compliance.

To boost compliance, bolus injectors are being developed with human factors as one of the key parameters. It comes as no surprise that most patients dislike injections, particularly those that are self-administered (Cox & Stone, 2006). Patient safety, ease-of-use, and comfort are some of the most important aspects of self-administration.

As one company developing bolus injectors, we began with a focus on painless injection of vaccines. We then transferred our knowledge of human factors and painless injections to this new field to make self-administration of high-volume biologics possible and palatable for patients. Doses for some of these biologics can be as large 20 mL. Without a new delivery system, such big doses could not be delivered subcutaneously and would have to be administered intravenously by a healthcare professional.

To make self-injection safe, easy, comfortable, and convenient for patients, yet cost effective for the pharmaceutical industry and payers, the more sophisticated new drug delivery devices are differentiated from legacy injection systems by the following:

• Utilize standard vials or cartridges, so no change to the primary container is required. This eliminates long-term drug stability issues with non-standard containers.  This also eliminates the need to develop a new manufacturing process and line to fill and insert a custom container into a device.
• Incorporates a unique ‘pause’ feature, where the user can easily pause the injection at any time if they experience any discomfort.
• Automatically warms the drug as the injector is filled, thereby eliminating the typical 30-minute or longer wait time to use the device for a refrigerated drug.
• For lyophilized drugs, completely automates mixing, removing any patient variability from the mixing process.
• Uses only standard intravenous-set materials in the drug delivery path, minimizing short-term material-drug compatibility issues.
• Uses the smallest available cannula size, typically from 29g to 33g, optimizing patient comfort.
• Very small in size, with a low profile to eliminate problems associated with adhering larger, heavier devices to the body.
• Environmentally friendly—no electronics or batteries to remove or recycle, and total volume of materials and packing is less than a standard IV set.
• Can subcutaneously inject from 1 mL (syringe dose) to 20 mL (high volume).
• Customizable drug delivery rate, duration, volume, and needle size.

User Friendly Self-Administration

Biologic Drugs

According to the FDA, biological products, of which biologic drugs are one example, are composed of: …sugars, proteins, or nucleic acids, or a combination of these substances. They may also be living entities, such as cells and tissues. Biologics are made from a variety of natural resources—human, animal, and microorganism—and may be produced by biotechnology methods. Gene-based and cellular biologics, at the forefront of biomedical research today, may make it possible to treat a variety of medical conditions, including illnesses for which no other treatments are available. Research continues to develop more biologics that will help treat medical conditions or add to existing treatment option. (U.S. Food and Drug Administration, 2008)

Minimizing patient errors and confusion has been an engineering and design challenge for bolus injector developers.

Today’s most sophisticated bolus injectors coming to market require only four steps:

• Insert a standard drug vial/cartridge into the transfer package.
• Remove the filled injector from the package when prompted.
• Place the injector on the skin.
• Push one button.

Their easy-to-follow directions with illustrations printed on the transfer container further reduce any confusion.

As an advance in injectable drug delivery devices, bolus injectors may provide greater safety for patients and healthcare workers by eliminating the risk-fraught steps involved in using conventional syringes. These include removing the syringe cap, drug preparation, inserting a needle, and covering and disposing of needles. With the wearable bolus injector we are developing, for example, the needle is never seen or exposed to the patient. Rather, the needle is automatically inserted after the injector is adhered to the patient skin and the button is pushed to begin treatment. At the end of the injection, the needle is automatically retracted and locked out, allowing for safe and convenient disposal of the system, and the patient is discreetly alerted with tactile, audible, and visual cues.  

With the advent of bolus injectors for self-administration, patients may no longer need to travel for treatment facilitated by a healthcare provider. For example, intravenous administration of the drug Herceptin for the treatment of breast cancer takes 30 to 90 minutes in a healthcare facility. Subcutaneous administration of the same dose with a bolus injector would take just 2 to 5 minutes at home. Not only is treatment at a healthcare facility time-consuming, but costs can be astronomical. A recent New York Times article, “Even Small Medical Advances Can Mean Big Jumps in Bills” (Rosenthal, 2014), cited a $133,000 charge for a single infusion for psoriatic arthritis at a hospital outpatient clinic—of which the insurer paid $99,593.

Fewer Needlestick Injuries for Healthcare Workers

Aside from increasing patient convenience and reducing costs, there is also the safety of healthcare providers to consider. Removing them from the drug administration process could result in far fewer needlestick injuries, which every day endanger those who render treatment with parenteral or intravenous injectables.

This is no small problem. According to the World Health Report (2002), of the 35 million healthcare workers, 2 million experience percutaneous exposure to infectious diseases each year. The report further notes that 37.6% of Hepatitis B, 39.0% of Hepatitis C, and 4.4% of HIV/AIDS cases in healthcare workers around the world are due to needlestick injuries. Though nurses are at the greatest risk, needlesticks can impact all other healthcare workers and individuals equally. In 2008, a study by the American Nurses Association (ANA) found that an astounding 64% of nurses surveyed reported an accidental needlestick injury. In 74% of these, the needle was contaminated.

Treating needlestick injuries is expensive. The U.S. Centers for Disease Control and Prevention (CDC) estimates direct costs for testing and treatment can range from $500 to $3,000 or more per injury. In case of an infection, these costs are multiplied. The CDC further estimates that 385,000 needlestick injuries are reported annually in U.S. hospitals, and the European Agency of Occupational Safety and Health (2003) puts the number of needlestick injuries that occur annually worldwide at roughly two million.

Top Clinical Indications for Bolus Injectors

According to analysts, cancer and related conditions are expected to be the areas of greatest opportunity for bolus injector use. Other prominent target diseases are likely to be autoimmune diseases, blood disorders, and genetic disorders. The list includes, but is not limited to:

• Rheumatoid arthritis
• Multiple sclerosis
• Hemophilia
• Myasthenia gravis
• Lupus
• Vasculitis
• Sickle cell anemia
• Numerous cancers
• Crohn’s disease, ulcerative colitis, and other digestive disorders
• Duchenne muscular distrophy, Pompe disease, and other genetic diseases
• Infectious diseases such as HIV, ebola, and CMV diseases
• Transplantation
• Inflammatory diseases
• Cardiovascular diseases
• Respiratory diseases
• Musculoskeletal disorders
• Eye diseases
• Skin diseases
• Neurologic disorders

Status of Bolus Injectors

Currently, bolus injectors are available for investigational use only pending U.S. FDA clearance and approval by worldwide regulatory bodies. The first bolus injector commercial launch is expected in 2015, according to analysts.

The market for bolus injectors is expected to grow rapidly, to $8.8 billion in the next 10 years. One of the greatest promises of bolus injectors, and the reason they will likely be adopted by all the stakeholders in the industry, is that they have the potential to lower healthcare costs substantially since patients will no longer need to visit a healthcare facility for drug administration. Increased patient compliance is also expected to generate cost savings while increasing patient satisfaction. By enabling convenient, safe, and easy at-home self-administration of large molecule or viscous drugs and many medications that today
are delivered intravenously, bolus injectors may revolutionize treatment of chronic conditions.

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Michael Hooven is CEO of Enable Injections and may be contacted at info@enableinjections.com.

Hooven, M. (2014). Bolus injectors: Medication adherence, safety and convenience. [Innovation]. Patient Safety & Quality Healthcare, 11(6), 16–19.

References

American Nurses Association. (2008). 2008 Study of Nurses’ Views on Workplace Safety and Needlestick Injuries. Retrieved from http://www.nursingworld.org/Content/occupationalhealth/OccupationalResources/2008SafetyandNeedlestickStudy.pdf

Cox, D., & Stone, J. (2006). Managing self-injection difficulties in patients with relapsing-remitting multiple sclerosis. The Journal of Neuroscience Nursing, 167-171.

Dunbar-Jacob, J., & Mortimer-Stephens, M. K. (2001). Treatment adherence in chronic disease. Journal of Clinical Epidemiology, 54(Suppl 1), S57–60.

Goldberg, E. L. , Dekoven, M., & Coyle, A. (2009). Patient medication adherence: The forgotten aspect of biologics. Biotechnology Healthcare, 6(2), 39-42, 44.

Lahue, B. J. (2012). National burden of preventable adverse drug events associated with inpatient injectable medications: healthcare and medical professional liability costs. American Health & Drug Benefits, 5, 413-422.

Murrow, T., & Felcone, L. H. (2004). Defining the difference: What makes biologics unique. Biotechnology Healthcare, 1(4), 24–26, 28–29. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564302/

Ostenberg, J., & Blaschke, T. (2005). Adherence to medication. New England Journal of Medicine, 353, 487-497.

Piette, J. D., Wagner, T. H., Potter, M. B., et al. (2004). Health insurance status, cost-related medication underuse, and outcomes among diabetes patients in three systems of care. Medical Care, 42, 102–9.

Robiner, W. N. (2005). Enhancing adherence in clinical research. Contemporary Clinical Trials, 26, 59–77.

Rosenthal, E. (2014, April 5). Even small medical advances can mean big jumps in bills. The New York Times. Retrieved from http://www.nytimes.com/2014/04/06/health/even-small-medical-advances-can-mean-big-jumps-in-bills.html?ref=health&_r=1

U.S. Food and Drug Administration. (2008, July 25). FDA 101: Biological Products. FDA Consumer Health Information. Retrived from http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/ucm048367.pdf

World Health Organization. (2003). The world health report 2003. Retrieved from http://www.who.int/whr/2003/en/