By Aktiv Pharma Group.
Automatic self-injection devices used for administering first-line treatments for nerve agent poisoning and other life-threatening conditions are about to become a lot more reliable and user friendly thanks to a Colorado company, Aktiv Pharma Group. Aktiv has developed the next generation autoinjector platform to address shortcomings of marketed autoinjectors and will begin commercial manufacturing in 2024 with deliveries starting in 2025. The new autoinjector named ARAI was designed specifically to meet the stringent requirements of the US Department of Defense (DOD) for medical countermeasures (MCMs) used by soldiers on the battlefield. As a result, the ARAI autoinjector delivers unprecedented ruggedness and ease of use and supports a wide range of treatments while maintaining operational uniformity.
Setting a New Standard
Autoinjectors have come a long way since the first atropine autoinjector was developed in the 1960s as a nerve agent antidote, but innovation has been largely restricted to autoinjectors used in routine treatment of chronic conditions. Emergency-use autoinjectors delivering life-saving treatments for conditions like nerve agent poisoning, seizures, and allergic reactions have not received the same level of attention. As a result, MCMs today are administered with autoinjectors that do not meet modern reliability standards and with autoinjectors that were never designed for use in chemical and biological defense. The need for a purpose-built MCM autoinjector has remained unmet, but this situation is about to change.
In 2012, Aktiv was growing a portfolio of drug delivery systems built around a glass-free flexible drug container technology it had developed to address the limitations of rigid glass containers. At the same time, the DOD was searching for a solution to its autoinjector problem, seeking a more rugged, easier to operate, and reliable autoinjector that could be used with a variety of existing and future MCMs. Such a device did not exist however and had to be designed and built from the ground up. Recognizing the potential of Aktiv’s novel drug containers, the DOD selected the company to develop the next generation autoinjector. With the DOD requirements in hand, Aktiv set out to work and over a period of 5 years developed ARAI from a concept to the advanced prototype stage where the device was ready for integration with MCMs. Subsequently, the agency responsible for supplying MCMs to the Strategic National Stockpile (SNS) awarded Aktiv a contract to develop and establish manufacturing of an ARAI pralidoxime chloride (2-PAM) autoinjector. Aktiv’s role in supplying the SNS was cemented in 2022 with a contract to deliver up to 2 million units of ARAI-2PAM, which will be the first product of six in the ARAI pipeline to reach the market, with others soon to follow.
ARAI Autoinjector Features and Platform Approach
Aktiv has developed ARAI to be simple, lightweight, user-friendly, highly intuitive to operate, and adaptable to a range of MCMs without changing the form factor or operational procedures. It features single step arming and single step activation that triggers injection automatically synchronized with needle deployment and retraction. Pressurized gas powers the injection cycle, deploying the needle and compressing the flexible drug container to deliver the drug. After delivery is complete, the needle is fully retracted back into the autoinjector.
ARAI was developed not as a single device, but as a platform that can support many variations. Variations of ARAI developed to-date include configurations with dose volumes from <1mL to 5mL, a dual-drug configuration where drugs are stored separately and each is injected through its own needle, and a reconstitution configuration which enables automatic reconstitution of drugs formulated in dry form. The platform supports up to four drugs stored separately and delivered simultaneously. All configurations share the same basic components and manufacturing equipment. The platform approach reduces training and logistical burden for the customer, and can reduce the number of autoinjectors that users have to carry.
Key Innovation
The combination of flexible drug container and pressurized gas power source is the central feature of ARAI differentiating it from all other autoinjectors that provides for unparalleled reliability while also enhancing versatility of the platform. Rigid containers require a moveable plunger which is associated with an inherent risk of leaks, especially in transport. There is also a risk of plunger binding to container walls and the autoinjector power source not being able to generate a sufficiently high force to overcome it. The flexible container in ARAI has no moving parts and is permanently sealed. Drug is extracted by piercing the container with the double-ended needle and applying gas pressure to container walls to expel the drug.
Another advantage Aktiv’s flexible container technology provides is the simplicity of implementing automated reconstitution. The container can be configured with two adjacent compartments separated by a peelable seal, where one compartment stores a dry formulation and the other stores its diluent. Applying pressure to the diluent compartment peels the seal to merge the compartments, mixing their contents. This function happens automatically during arming step when cap is removed and does not require any additional operation from the user.
Critical Importance of Reliability
Reliability of an autoinjector intended for delivering lifesaving MCMs is unquestionably essential, yet remains a weak point of marketed autoinjectors. Frequent failures of autoinjectors prompted the US Food and Drug Administration (FDA) in 2020 to institute a requirement that manufacturers demonstrate lower than 1 in 100,000 failure rates, or 99,999% reliability, also referred to as “five nines”. For ARAI the bar was even higher, compounded by the DOD requirements that the autoinjector functions when subjected to extreme environmental conditions. Nevertheless, ARAI not only met the FDA’s reliability requirement, but reached 99.9999% (six nines) reliability in independent testing performed by the US Government. This result clearly demonstrates the inherent reliability of the ARAI design and Aktiv’s commitment to product quality.
Focusing on the User
While reliability is vital, autoinjector design must also account for the user and the use environments. Unlike consumer products, MCMs autoinjectors are used in challenging environmental conditions, potentially chaotic and with low visibility, by users under duress wearing heavy protective equipment. ARAI takes this into consideration, with the device size and shape optimized for handling through thick rubber gloves, a large and clear label, and tactile, visual, and auditory feedback provided to the user throughout the injection process. While all ARAI devices share the same form factor, their endcaps have distinct geometries, allowing the user to identify the drug they contain by touch alone. The needle cap removed from the autoinjector during arming has a lanyard with a carabiner clip that makes operation more intuitive. The lanyard specifies the drug and the dose and can be attached to the casualty to serve as a record of MCM administration.
What’s Next?
Aktiv’s current pipeline of MCMs autoinjectors includes 2-PAM, scopolamine, atropine, reconstitution atropine, and atropine and 2-PAM dual-injection. In addition to these nerve agent antidotes, Aktiv is developing a tranexamic acid autoinjector under a DOD contract. This product portfolio will continue to grow, and the company is open to developing other products on the ARAI platform for international customers, leveraging Aktiv’s vertically integrated in-house development and manufacturing capabilities, strong quality and regulatory teams specialized in combination products, cleanroom assembly facilities, and sterile fill-finish. To learn more, meet the Aktiv team in person at NCT Europe 2023 and visit aktivpharmagroup.com.
Aktiv has developed the next generation autoinjector platform, ARAI, as a simple, user-friendly, reliable, durable, and adaptable lifesaving device that meets stringent battlefield requirements of the DOD while also exceeding the FDA’s reliability standards. Aktiv is excited about its future and is well postured to provide the ARAI autoinjector for a host of new treatments to ensure that a wider array of lifesaving medicines is available to those facing their most critical time of need.
