Why This Dual Chamber Auto-Injector Won Three Design Awards

August 22, 2023 - On June 19, 2023, Philips–Medisize was recognized for its SKYTROFA auto-injector at the Red Dot Design Awards in Essen, Germany — its third award for its unique design. The device offers a unique approach to injection that minimizes waste and prevents patient errors. 

SKYTROFA, manufactured by Ascendis Pharma Inc, is a weekly subcutaneous injection of human growth hormone to pediatric patients with growth hormone deficiency (GHD). The United States Food and Drug Administration (FDA) approved the drug on August 25, 2021, for children over 1 who weigh at least 11.5 kg. Shortly after, on January 11, 2022, it was also granted regulatory approval in Europe. 

The once-weekly injection significantly reduces the number of injections required to treat patients effectively, but a lyophilized formulation required a unique preparation and delivery approach, prompting Ascendis to reach out to Philips–Medisize to develop an injection device. 

A collaborative effort between the two organizations contributed to developing the SKYTROFA auto-injector and drug delivery system. 

THE AUTO-INJECTOR 

“SKYTROFA is an injectable drug product developed by our customer, Ascendis. It’s a sustained-release growth hormone product,” Paul Erik Fabricius, director of Front-End Innovation at Philips–Medisize, located at the Global Innovation and Development Center (GID) in Europe, told LifeSciencesIntelligence. 

Unlike standard treatments for this condition, this formulation allows patients to forego daily injections, replacing them with weekly injections. However, the new formulation includes a lyophilized product which poses additional concerns. 

The medical device, developed by Philips–Medisize, is unique in its ability to reconstitute and deliver medication while ensuring stability of a lyophilized product during storage in a dual-chamber cartridge to be inserted into the drug delivery device. 

One chamber has the lyophilized product, while the other has the liquid to reconstitute the medication. Having a lyophilized product has a significant benefit. It can be stored at room temperature and doesn’t require special refrigeration, which supports a robust supply chain as medications are less likely to be wasted. 

On the other hand, having a product that must be reconstituted increases the complexity for patients and their families. Although self-administration eases some burdens on patients and healthcare professionals, parenteral drug delivery is more complex than oral. 

“One decision from our customer side was to aim for a dual-chamber cartridge solution for ease of use, compared with using a standard vial for the lyophilized product,” explained Fabricius. 

Another goal was to make the needle as small as possible, as the drug is intended for a pediatric population. The needle is 31 gauge, which is minuscule compared to standard needle sizes. According to Fabricius, the needle of this size can barely be felt by patients. 

With those two requirements, reconstitution can be a complicated process requiring guidance. Additionally, the injection process requires significant force to ensure the viscous fluid can be ejected through a thin needle. 

“When the patient has loaded a dual chamber cartridge into the auto-injector, the device automatically mixes the lyophilized drug and water, making it ready to inject.,” added John Norskov Christensen, senior project manager in contract development at Philips–Medisize. 

Using a device instead of doing it by hand, the patient can replicate the process the same way each time. 

How Does It Work? 

To start, there is a protective cover on the auto-injector that the patient removes from the device before beginning the process. Before even beginning injection, the device runs a self-test, ensuring enough power for one injection. There are lights on the device and sounds that indicate to the patient that the device is charged enough for the injection. 

After that, the patient can insert the cartridge, a single-dose dual-chamber syringe with a color code. The device can detect the color code on the prefilled syringe and follow a dedicated drug program. 

The reusable auto-injector will automatically mix the liquid with the lyophilized drug. 

“There are different programs for the individual dose sizes because it takes different times for the water to mix with the lyophilized drug,” noted Christensen. “Patients can follow the reconstitution with the progress bar based on how far along it is in the process. It guides the user on when to do something.” 

Alongside the automatic mixing, the drug product requires manual mixing as well. A certain number of inversions are needed to ensure the drug is sufficiently mixed and dissolved into the fluid. Without the inversions, there is a chance that the drug won’t fully dissolve in the viscous liquid and be delivered through the needle. These inversions are guided and controlled by the device. 

The device makes an audible sound for every inversion and lights up, indicating a complete inversion. Once the total number of inversions is completed, the device beeps to indicate that the injection is ready. 

At that point, the patient can remove the needle cover and bring the green skin contact against the skin. 

“It automatically starts when the green skin contact is pushed back, then it automatically empties the cartridge,” said Christensen. 

The injector applies force to inject the high-viscosity fluid over 10–12 seconds. Once the medication has been delivered, the device beeps and lights up to indicate to the user that the injection has succeeded. After removing the device from the injection site it will reset the mechanics, allowing the user to remove the cartridge and replace it the following week. 

Safety 

In addition to functionality, safety guards are in place when delivering the biological drug with this device. 

“Part of the safety in a reconstitution process is that patients don’t waste product. The device has an orientation sensor, which means that, during the reconstitution, if you tilt the device so the needle doesn’t point upwards, it simply stops and gives a warning sound,” noted Christensen. 

Once the device is back at the appropriate orientation, the device continues. It prevents simple and common errors, which helps minimize drug wastage and improves the patient experience. 

Fabricius emphasized that the device is intended for self-injection at home. The device doesn’t provide needle safety in a healthcare setting. Instead, it has a hidden needle even after the needle cover is removed. Although the needle shield provides the patient some protection, for healthcare providers, it does not safeguard against potentially dangerous needle sticks. 

“In principle, the needle is covered inside the green part, but it’s not a safety needle,” added Christensen. 

“When discussing a professional setting, it comes with that mutation. We have ideas to handle that needle safety, but this product doesn’t do that yet,” said Fabricius. “So, if we are talking about an application that needs to go into a hospital or something like that, it would be a different variant than what you’ve seen here.” 

Sustainability 

One of the most favorable aspects of this product is its sustainability. As climate change continues to alter human health, pharmaceutical companies and healthcare providers are searching for ways to minimize medical waste. 

“The auto-injector is a reusable personal device. It lasts for four years of use, typically. The only thing patients dispose of each time is the fully emptied cartridge that contained the lyophilized drug. So, the empty cartridge and the needle are thrown away as soon as it’s used,” explained Christensen. 

The device is rechargeable; one full charge can last up to three months, depending on the drug concentration and volume in the cartridge. 

“The reason for the four years is that it’s the normal period that the patient is treated with growth hormone. There can be some that need a longer time, but it’s based on that design or input from our customer in the beginning,” said Christensen. 

While the device is designed to last four years before being disposed of, it can effectively handle 200 injections, which can be delivered in those years. Additionally, the device improves sustainability, requiring only the small drug chamber and needle to be thrown out. 

“Because it is an electronic device, all the parameters involved in this process — for example, the reconstitution time, the need for manual mixing injection parameters, injection time, and dwell time— are controlled by just software,” said Fabricius. “So, it is straightforward for us to reconfigure the technical platform to another application. It’s something we expect to see in the future.” 

As the healthcare industry continues to shift toward low-waste alternatives, reusable auto-injectors may replace pen injectors for other treatments, including autoimmune diseases such as multiple sclerosis and diabetes. But before these products can be modified for other conditions, clinical trials must be conducted to evaluate their efficacy and usability. 

Editor's Note: Quotes and associated text have been updated to improve clarity and accuracy.