Imagine one morning you wake up, smell smoke, and see a fire starting in the kitchen. Next, you grab the fire extinguisher, but first must fill it, screw on the valve, and pressurize it before you can use it to put out the fire! Requiring so many manual steps before using an emergency device is absurd, but this was the standard experience for emergency medical treatment prior to the availability of autoinjectors for drug delivery.
The autoinjector began with a simple vision: to be a bridge between a medical emergency and more definitive care for our military. It needed to enable a person to self/buddy treat under dire circumstances. It had to be easily available, ready to use, fully assembled, simple to operate, and able to inject through multiple layers of clothing and protective garments. The simplicity and ease of administration was especially critical considering the use conditions. When your life or the life of someone you care for is on the line, the most uncomplicated of tasks can become difficult.
Autoinjector use quickly expanded beyond the original battlefield context to protecting astronauts in space and patients on playgrounds, in offices, and at home. Autoinjectors and the sterile injectable products they deliver have evolved well beyond emergency care to enhance the quality of patients’ lives and enable home-based therapies once thought impossible. Although autoinjectors are well known, many may be unfamiliar with their fascinating history. In this article, we explore how the autoinjector came to be and how it has changed the world since its creation.
The Predecessor to the Autoinjector
Prior to the development of the autoinjector in the late 1950s, military personnel used a product called a syrette. Its appearance was similar to a travel-sized toothpaste tube, but with a needle. In the event of chemical poisoning, a soldier would be expected to unscrew and remove a cap to expose the needle, then push down on a tiny stylus inserted into the needle cannula, which would pierce an aluminum seal and open a fluid path. The soldier would then push the needle through several layers of clothes into their leg and squeeze the thick medication into the muscle. Remembering so many steps and executing them correctly and rapidly during a medical crisis in a chaotic emergency situation presented serious challenges and impeded successful medical treatment. While the syrette was an improvement over a vial and syringe, a human factors study wasn’t necessary to conclude that a syrette still wasn’t the most effective method of administering emergency care medications.
Stanley Sarnoff, an NIH cardiologist, learned about this issue and decided there had to be a better way to deliver treatment in the field. He formed a company called Rodana Research, a combination of his daughter’s and son’s names, and developed the first autoinjector around 1956. Their mission was simple and focused: develop ready to use automatic syringes to save lives. In the first quarter century of production, the company produced 53 million autoinjector units.
From the Battlefield to Space, Then Homes
In the early days of the space program, NASA flight surgeons were challenged with supplying astronauts with injectable medications in emergency care contexts. Recognizing that vials, pre-filled syringes, and even syrettes were not suitable, in the early 1960s they turned to Rodana to supply a variety of emergency medications in autoinjectors for astronauts’ medical kits during the Project Mercury space flights. The kit initially included three autoinjectors containing an anti-motion sickness medication, a stimulant, and a vasoconstrictor for treating shock.
Next, Dr. Sarnoff and Rodana engineers noted that civilian patients with severe life-threatening allergies faced similar challenges; in emergency situations when they needed fast treatment, they were expected to remember and execute a complex series of steps to prepare a syringe for injection. Sarnoff saw this firsthand at a dinner with friends. A woman in the group was carrying a vial of epinephrine and a syringe. If she experienced a severe allergic reaction to food, she (or someone else) would need to draw up the medication in the correct dose and administer it. This was the standard of care at the time, but was quickly replaced by an autoinjector designed by Dr. Sarnoff’s team (the ComboPen®, circa 1970) that evolved into Viatris’ EpiPen® (developed, filled, and packaged by Kindeva Drug Delivery) — perhaps one of the best known autoinjectors globally. Imagine how many lives have been saved by using autoinjectors because of this chance encounter at a dinner party so many decades ago.
Sleeker, Safer, and Sturdier Technology
Over time, autoinjectors continued to evolve based on the expansion of emergency injectable medications and use conditions. As an example, in the 1970s, the U.S. military adopted an autoinjector kit known as a Nerve Agent Antidote Kit (NAAK). This was a set of two autoinjectors, each carrying a different medication. Personnel would receive three sets of the NAAK. Each set contained the two autoinjectors on a plastic clip. To administer the autoinjectors, the soldier would pull each one from the clip to remove the safety release. While this was certainly more efficient than the syrettes of the past, it still took time to remove and administer both autoinjectors. The kits were also bulky and required soldiers to carry six autoinjectors in total. This led the military to explore the possibility of a single autoinjector for treating chemical poisoning.
Initial attempts to co-formulate the medications in a single autoinjector were not successful. Mixing the medications resulted in inferior bioavailability and decreased shelf life versus the NAAK. To meet the needs of the military, drug separation during storage and administration was critical, but this also had to be achieved with a single autoinjector no larger than one of the two autoinjectors in the NAAK.
The solution was BinaJect®: an autoinjector with two liquid drug chambers. This design maintains separation of the two drugs over the entire shelf life. BinaJect® delivers the drugs in a proprietary manner which results in very little mixing of the drugs in vivo and no mixing within the device. This provides an equivalent clinical outcome to two injections, while saving time, requiring fewer steps, and reducing the weight military personnel need to carry.
Today, acute and chronic use of autoinjectors represent the vast majority of growth and product diversity. The simplicity and ease of use of this technology make this possible, keeping treatment easy, reliable, discreet, and safe. Enabling injections where patients live, work, and play not only improves patient experience and compliance, but also helps lower medical expenses and reduces the burden on the healthcare system. As autoinjectors’ range of capabilities expands (e.g., total volume, range of viscosities, combination of dry and liquid formulations, mixing in device, etc.), the number and types of therapies they can serve expands as well. The expansion of options for autoinjector use is driving unprecedented demand for autoinjectors and similar drug delivery technologies. For example, the recent surge in the use of autoinjectors for GLP-1 products is the quintessential example which demonstrates the benefits and potential of autoinjector drug delivery.
Today, there are 118 autoinjector combination products marketed globally, with 70 more in the pipeline (PharmaCircle, 2021). Over 11,000 patents have been granted for various autoinjector platforms, components, and features. Within the U.S., 53.3 million autoinjector combination product units were sold in 2022, with a total value of $86.7 billion; in the EU, 38.7 million units were sold, with a value of $11.3 billion (IQVIA, 2023). A significant number of these were produced by Kindeva Drug Delivery. The impact of the autoinjector’s invention has been global and transformative, saving and improving millions of lives. The market for autoinjectors continues to expand, bringing convenient and easy-to-use treatment options to more patients worldwide.
Be Part of the Future of Injectables
Today, Kindeva is supporting pharmaceutical product innovators and patients by offering industry-leading CDMO services from development, GMP manufacturing, and technology solutions across pulmonary, nasal, transdermal, intradermal, and injectable routes of administration.
Kindeva’s decades of experience supplying commercial sterile injectable medicine and autoinjectors enable us to uniquely offer product innovators a co-located supply chain solution for bulk formulation, fill-finish, device assembly, and final packaging and labeling. Kindeva is device agnostic, affording flexibility for accessing our own proprietary platforms or utilizing third-party devices.
Lastly, Kindeva’s new 155,000-square-foot sterile injectables facility in St. Louis, MO, will be operational in mid-2024. With ~$200M invested capital, our new Bridgeton center of excellence for aseptic fill-finish is a fully Annex I compliant injectable contract manufacturing facility. Fully automated filling lines embracing isolator technology as its cGMP standard, it will be initially capable of producing more than 100 million vials, cartridges, and pre-filled syringes annually. Visit Kindeva to learn what is possible when you combine forces with us for drug-device development and manufacturing.
References
(2021) Injection Devices. PharmaCircle
“AI Market US and EU.” IQVIA. Retrieved December 18, 2023