SPECIAL FEATURE - Injection Devices: Designing Simplicity, Safety & Adherence Into One Delivery System

The global injectable drug delivery devices market is expected to show significant growth in the coming years as manufacturers introduce technological advancements and product innovation meant to improve convenience, compli­ance, and ease of administration of parenterals. Additionally, the increasing preference for at-home self-injection is driving the market as patients prefer to continue to avoid healthcare settings post-COVID. With all of this taken into ac­count, one market study predicts the global market to reach almost $26 billion by 2025, up from $15 billion in 2020.¹ However, another report values the global market at $42.76 billion in 2021 and expects it to reach $50.9 billion in 2025.²

How the numbers will play out is yet to be determined, but the studies do highlight the focus on single-use and reusable systems. Disposable-use prefilled syringes (PFS) are increasingly used due to the prevalence of chronic diseases and the growing number of biologics best delivered by syringes. Single-use autoinjectors are also poised to experience increased demand, particularly with the growing pervasiveness of anaphylaxis disorders. Autoinjectors also provide a convenient alternative to manual syringe injections for subcutaneous administration.

But their reusable brethren, such as pen injectors with prefilled car­tridge, are also proving viable syringe alternatives. These injectors can per­form hundreds of injections, with pa­tients controlling the speed of delivery to minimize pain or discomfort during use.

“Making injection devices partially reusable is a cost-saving strategy,” says William Fortina, Business Devel­opment Director, Duoject Medical Sys­tems. “Ideally, the device’s mechanism and/or electronics are the reusable parts of the system – as these are often the costliest – and the drug containers and needle are one-time use.”

Another cost-saving strategy that several large pharmaceutical compa­nies are deploying is to develop a de­vice platform for multiple drug products in their portfolio, says Mr. Fortina. “This allows them to spend re­sources on a single significant devel­opment program, for one optimal injection device, which then requires minimal customization for each sub­sequent product line.”

Despite efforts to make better, safer, simpler injection devices, patient adherence is still a challenge associ­ated with self-administration. This has resulted in the emergence of smart devices, such as wearable injectors, which share patient data with health­care providers to ensure compliance. And while it is expected this sector will continue to grow, some industry insid­ers warn against making these devices too intrusive.

“Smart devices, interconnectivity, and related technology provide real-time data to healthcare providers for analysis, but these device additions should not increase risks, including patient understanding of treatment delivery, or jeopardize compliance,” says Michael Denzer, Vice President of Technical Solutions at Kymanox. “Data collection needs to be “passive” to the patient. In other words, invisible to the patient’s use of the device so that the collected data provides a true benefit to the end user. If these design consid­erations can be implemented without impacting the patient or how they ad­minister and receive treatment, then smart devices can provide advantages to the patient and the industry.”

This annual Drug Development & Delivery report takes a deep dive into the myriad injectables that are either currently in development or recently introduced to the market.

Aptar Pharma: RFID-Enabled Rigid Needle Shields for Unit Serialization & Track and Trace

Today, traceability of parenteral drug products is performed at the batch level. Health and regulatory au­thorities are currently looking into im­plementing unit serialization (Policy paper on traceability of medical prod­ucts, WHO, 2021) to improve trace­ability from production through to patients. “Individual container trace­ability could dramatically improve pa­tient safety, preventing potential mix-ups, clarifying accountability, and simplifying investigations in case of deviation during fill-finish operations,” says Audrey Chardonnet, Business Di­rector, Aptar Pharma. “Current strate­gies are reaching their technical limitations and new approaches must be considered to address future re­quirements.”

Most identification strategies for injectable drugs rely on physical stick­ers applied onto the drug container during filling, a method that Ms. Chardonnet says is hardly applicable to unit serialization. Different tech­nologies were considered and eventu­ally narrowed down to two options: the engraving of a 2D-matrix on the glass container or digital chips. 2D-matrices are relatively easy to engrave on the glass, but require the installa­tion of engraving equipment – either on the filling or glass manufacturing lines – and advanced camera systems for reading the matrix. Because it is physically engraved on the glass, the matrix cannot be read through sec­ondary packaging and requires the container to be oriented on the filling line to allow reading. Adding a digital chip to the packaging allows individ­ual serialization and brings further benefits. Industrial implementation re­quires the addition of a contactless reader to identify the dose at any point during the process – even through a secondary packaging – and the tag can be edited to attach more informa­tion on-the-go.

“The idea of unit serialization is often associated with prefilled syringes (PFS),” she says. “In addition to well-documented advantages over multi-dose or single-dose vials, including ease-of-use, safety, and reduced drug wastage, unit serialization eliminates the need for a distinct injection device, thus ensuring the patient receives the dose directly from the device that car­ries the tag, reducing risk of mix-ups before the injection.”

Aptar Pharma’s RFID RNS is a digitally-enabled RNS that leverages RFID tech­nology, miniaturizing and embedding it in the RNS plastic shell. This chip acts as a tag that can be read and ed­ited at any time from the filling process to the time of injection. “The RFID RNS enables easy implementation of unit-dose “track and trace” processes on the filing lines thanks to contactless reading/editing of the RFID chip,” Ms. Chardonnet explains. The RFID RNS al­lows high-throughput unit identifica­tion without impacting the filling lines beyond the addition of a reader.

BD Medical Pharmaceutical Systems: Usability is Built Into All Devices

At BD, the “smartification” of delivery devices is guided by a user-centric approach. Extensive human factors studies help to ensure that added functionalities serve to enhance, not detract, from usability. In fact, BD has conducted more than 80 human factors studies on its portfolio of products since 2010. Network security and environmental sustainability (potential pollution from electronic waste) are also critical issues every smart solution must address, says Beth DiLauri-McBride, Chronic Portfolio Marketing Director, BD Medical-Pharmaceutical Systems.

Beyond usability, new functionalities such as the ability to verify a drug’s authenticity, can be achieved through smart traceability solutions. “BD is developing a traceability solution that aims to reduce manufacturing mix-ups and help to provide manufacturing to point-of-care traceability in the long term,” says Marie-Liesse Le Corfec, Head of Portfolio Marketing for BD Medical-Pharmaceutical Systems. “This BD whole-system approach is based on simple, robust, and market-proven technologies and encompasses tagged and nested prefilled syringes, readers, and software as part of a fully tested and ready-to-use system.”

BD also is focused on developing robust PFS solutions for the delivery of sensitive biologics while ensuring that each solution has supply availability to meet customers’ demands. To achieve this, BD has developed an array of solutions for the testing and delivery of drugs or vaccines. “Most recently, we expanded our service capabilities and acquired ZebraSci,” says Ms. Le Corfec. “Also, our PFS portfolio includes both coated and uncoated stoppers and bare or siliconized barrels, using, for example, baked or cross-linked silicone.”

An example of BD cross-linked silicone technology is the BD NeopakTM XSiTM Glass Prefillable Syringe that helps protect against lubricant-drug interaction, while supporting the full gliding performance essential to innovative drug formulations aiming to increase payload.

BD SCFTM PremiumCoat^® Plunger Stoppers for chronic drug delivery applications help protect drugs from component interaction, while aiming to improve delivery system performance.

Bespak by Recipharm: Developing Connectivity Across a Range of Autoinjectors

Digital health provides many ben­efits when transitioning treatments into the hands of patients. When the phys­ical interactions between doctors and patients are reduced, smart, digitally connected devices can improve pa­tient engagement, record compliance, and monitor clinical effectiveness. “Adding digital features to autoinjec­tors without adding any additional user steps is key to the adoption of such new technology,” says Hans Jensen, Global Business Development Director of Bespak by Recipharm.

He says factors to consider in­clude:

• Minimal impact on device design – ensures the device is unchanged in terms of size, shape, and how it is operated, so patients don’t have to re-learn how to administer their medicine.
• Flexible interface architecture – en­ables integration into a connectivity suite that both patients and HCPs can use, and can be tailored to the usability needs of the target pa­tients.
• Bluetooth^® connectivity – harness wireless communication technol­ogy, so that patients can simply connect their device to their smart­phones without having to spend time setting up new and unfamiliar technology.

Bespak by Recipharm is develop­ing connectivity features that can be used across its range of autoinjectors. Its VapourSoft^® autoinjector platform, including Viscala^®, was designed par­ticularly for biologics and long-acting formulations. “Viscala delivers formu­lations with very high viscosities – something traditional spring-powered devices are struggling to achieve,” he says.

Viscala^® uses the proprietary VapourSoft technology, which uses liq­uefied gas as the power source, rather than a traditional spring. Mr. Jensen says the benefits of VapourSoft include the ability to generate high forces within the device without damaging the syringe, delivery through patient-friendly fine needles, constant force profile throughout the delivery phase, and easy adjustment of forces by se­lection of gas from range of available gasses.

Catalent Biologics: Helping Pharma Partners Post-COVID

Now that COVID-19 vaccines are in production and available, Catalent has seen some of its partners shift their focus back towards non-COVID related treatments, and this includes the growing interest in “off-the-shelf” (OTS) style autoinjectors. “Historically, route of administration decisions have been made later in development, with many innovators opting for providing drugs in vials in order to reduce drug/device development complexity,” says Brian Galliher, Principal Process Engineer, Catalent Biologics. “What is more apparent now is that pharma companies are working to address key end-user questions earlier, to enable a more patient-friendly experience as soon as commercial approval is achieved. This renewed focus on non-COVID indications earlier in develop­ment may lead to more self-injection options, such as OTS autoinjectors.”

Over the past year, devices as­sembled at Catalent for customers have included anti-needlestick devices and autoinjectors for biologics used to treat autoimmune disorders.

Credence MedSystems, Inc.: Enhancing & Facilitating Intravitreal Drug Delivery

While Credence MedSystems is scaling its Companion and Dual Chamber Reconstitution Syringe Sys­tems to meet demand from pharma customers, the company has also ad­vanced development of its ophthal­mology and gene therapy solutions. These therapeutic areas share some common requirements for drug deliv­ery, including the requirement to de­liver extremely low injection volumes with precise accuracy, the need for user-friendly solutions that do not en­cumber the procedure, and the need to maintain lower injection forces de­spite the possibility for high viscosity injectables.

Credence is developing the Micro-DoseTM Syringe System, de­signed to deliver a nominal dose ranging from 50μL down to below 20μL, with high accuracy. With Micro-Dose, the clinician simply presses on the plunger rod until it stops moving, explains John A. Merhige, Chief Com­mercial Officer, Credence MedSys­tems, Inc. The allowable travel length of the plunger rod determines the removing a source of user error. The device allows the user to control re­moval of the air bubble by turning the safety cover. “This helps prevent valu­able drug from being wasted during conventional air bubble purging, and can allow reduction of overfill require­ments, leading to economic benefits,” he says.

A sister product to Micro-Dose is Multi-Site™, which allows similar pre­cision but repeated administration of multiple doses from the same syringe in the same procedure. This product has application in certain ophthalmol­ogy applications, cosmetic applica­tions, and dental applications.

Additionally, as pharma manufac­turers develop biologics that require more viscous formulations, the ability to maintain lower injection forces be­comes critical, especially with intravit­real injections. Credence is developing an adjunct technology that can be used with its Micro-Dose and Multi-Site technologies called Force-AssistTM, which uses a levered advan­tage to reduce the force required to inject by roughly one-third of that which would be required in a tradi­tional delivery system. Mr. Merhige says: “With the delivery of viscous flu­ids through very narrow/high gauge needles, this technology can enable caregivers to maintain control of the injection and avoid discomfort to the patient, while still achieving precise low-dose accuracy.”

SHL Medical: Modular Platform Technology Addresses Today’s Self-Injection Trends

Subcutaneous self-injections are evolving as a preferred choice owing to the advances in biologic formula­tions. “As self-injection technology ma­tures, there is a compelling need for a flexible device platform that can be leveraged across a number of thera­pies without compromising injection experience or patient acceptance,” says Magnus Fastmarken, Director of Marketing at SHL Medical.

The evolution of SHL’s Molly^® de­vice technology corresponds to the growth of the autoinjector market. In­troduced in 2010 as a preconfigured solution, Molly has been applied in treatments for diseases such as Rheumatoid Arthritis, migraine, osteo­porosis, and atopic dermatitis, among others. Following the development of pharmacologic therapies targeting weight loss, Molly now also supports treatment for obesity.

“Molly’s modularization offers cost effectiveness in device manufac­turing and provides flexibility in the device designs and fill volumes, allow­ing for design modification according to specific combination product proj­ect needs,” says Mr. Fastmarken. He adds that the modular technology in both the 1.0mL and 2.25mL standard versions of Molly autoinjectors enables design customizations in the front and rear sub-assemblies of specific device projects while keeping the core components intact.

In response to the need to intro­duce different dosing volumes for dif­ferent target markets, SHL helped a pharma company lifecycle an existing product into the Molly and Molly 2.25 devices for hypercholesterolemia. “This not only demonstrates how Molly can support pharma companies in meeting their branding requirements, but also in accommodating patient-centric device designs to support pharma’s commercial strategies,” Mr. Fastmarken says. “With Molly, SHL seeks to reduce the development time and resources while ensuring compat­ibility between a drug product and the device. By sharing commonality of a modular platform, SHL is also able to share manufacturing assets across multiple Molly device projects, con­tributing to the optimization of costs, development timelines, as well as the overall environmental impact from producing and operating individual machinery.”

SHL has been working with Molly’s platform technology to de­velop digital initiatives supporting con­nected therapeutics to address the shift from administering injections in clinical settings to homecare settings. Mr. Fastmarken says digital interven­tions in self-injection devices need to provide flexible and sustainable offer­ings to facilitate different patient be­haviors and treatments. “We are in the development phase of solutions that can achieve the functionality and us­ability of a traditional autoinjector with additional features that allow for con­nected health capabilities, while miti­gating the environmental impacts.”

Mitsubishi Gas Chemical Co., Inc.: Staked-Needle Syringe Targeted to Biologics

Mitsubishi Gas Chemical Co., Inc. has been focusing on developing staked-needle syringes and plans to start providing samples in 2022. The targeted therapeutic is biologics and the targeted users are biopharma and conventional drug companies.

The staked needle syringe can de­crease the possibilities of needle-stick injury and eliminate the loss of time to attach a needle to syringe, according to Tomohiro Suzuki, Associate General Manager, New Business Development, Mitsubishi Gas Chemical Co., Inc. “Many customers have asked for staked needles, and we can change the needle length and gage based on requests and demands, so the sy­ringes will handle every viscosity.”

The new syringes are made of a multilayer plastic with a high oxygen and UV barrier. He says: “As there is an issue of breakage with glass con­tainers, and COP monolayer syringes don’t have sufficient oxygen or UV barrier protection, the new staked needle product avoids the risk of breakage and offers stability to oxy­gen- and UV-sensitive drugs.”

He adds that the multilayer plastic vial and syringe, OXYCAPTTM, will con­tribute to stabilizing every kind of drug.

Nemera: Finding a Balance Between Safety & Simplicity

For Nemera, the ultimate goal is to find this right balance between sim­plicity and robustness of drug delivery devices. Safety and ease-of-use are two of the crucial characteristics in ad­vanced parenteral devices. To that end, Nemera has been focusing on developing and manufacturing safe injection devices that foster patient ad­herence and improve the self-admin­istration experience as well as ease-of-use.

“Patients with chronic conditions who require lifelong medication need enhanced comfort to manage their treatment, particularly when self-ad­ministering complex, large-volume, high-value biologic drugs, such as monoclonal antibodies,” says Sever­ine Duband, Category Director, De­vices, Nemera. “They need a robust, advanced drug delivery device that also offers simplicity and ease-of-use. On the other hand, patients who have specific and complex conditions – such as oncology, neurology, hematol­ogy – also need safe devices to inject their complex drugs and to avoid hos­pital/healthcare professional interven­tion. This need is increasing with the trend of switching from intravenous to subcutaneous delivery.”

To address the increased trend to­ward self-administration of large-vol­ume biologics, Nemera’s key focus this year has been on the development of an on-body injector platform for complex, large-volume drugs (20mL) delivery, such as monoclonal antibod­ies with an adjustable flow rate to fit both patients’ and drugs’ administra­tion profiles. And, it is sustainable thanks to its reusable electronic part and drug-containing disposable ele­ment.

As an example, the PENDURA AD is a platform dedicated to manu­facturing a reusable pen injector that integrates an automatic, spring-dri­ven feature coupled with a side acti­vation button. Its technological solution allows the ergonomic loca­tion of the dose-release button on the side of the pen, ensuring stabiliz­ing the hand holding the pen by rest­ing it against the body during dosing, says Audrey Chandra, Cate­gory Project Manager, Nemera.

Owen Mumford Pharmaceutical Services: Expanding Platform to Address High-Volume Biologics

Owen Mumford Pharmaceutical Services has been focusing on its pas­sive safety syringes this past year. These are typically used for subcuta­neous administration of therapies for a variety of treatments, such as multi­ple sclerosis, Rheumatoid Arthritis, and Crohn’s disease. The addition of a needle protection safety feature en­sures patient safety and compliance with needlestick prevention regula­tions.

“We have expanded our UniSafe^® platform with the addition of a 2.25mL device,” says Michael Earl, Director of Owen Mumford Pharma­ceutical Services. “Like the existing UniSafe 1mL, the product features a spring-free design that prevents pre-activation during transit and provides a simple final assembly,” he explains. “From a patient perspective, the ab­sence of a spring helps with drug vi­sualization and checking in the syringe barrel before and during administra­tion, and also provides the same sim­ple administration technique as a prefilled syringe. Additionally, the ab­sence of a spring as well as preventing pre-activation in transit also helps with drug inspection prior to patient ad­ministration in addition to providing a longer shelf life of 3 years.”

He adds that the increasing num­ber of higher volume (>1mL) biolog­ics coming to market has resulted in the growth of 2.25mL prefilled sy­ringes and the need for associated safety devices. “The launch of UniSafe 2.25 makes it particularly suitable for delivery of these types of formula­tions.”

Stevanato Group: Platform Designed for Compliance & Speed to Market

During the past year, Stevanato Group has focused on pen injectors and emergency autoinjectors. The SG Alina® is a customizable pen injector designed to target diabetes, focusing on insulin and GLP-1 therapies.

“SG Alina promotes better com­pliance and more effective treatment, aiding efforts to reduce costs and im­prove quality of care,” says Adam Stops, PhD, Product Management Drug Delivery Systems, Stevanato Group.

Other advantages include: deliv­ery forces that suit all demographics; ergonomic design of the dose dialing; labeling space for enhanced readabil­ity; cap designed for ease of use and durability; and optimized dose num­bering.

The pen injector also has been designed as a platform to speed time to market for pharmaceutical compa­nies, while also bringing the benefits of Stevanato’s end-to-end solutions, such as glass products, automated as­sembly, and visual inspection equip­ment, as well as analytical services, says Dr. Stops.

Vetter: Leveraging Devices for a Range of Therapies

Vetter specializes in filling, assembling, and packaging of injection systems, and is keeping a close eye on several areas where the injectable product landscape is evolving rapidly. The company has already pursued several projects to evaluate a range of different pens, autoinjectors, and wearable systems.

“We’re particularly interested in how we can leverage these devices for therapeutic areas such as autoimmune diseases, growth disorders, migraine, oncology, and Type 2 diabetes,” says Markus Hoerburger, Product & Service Manager at Vetter. “Patients with these conditions may derive particularly valuable benefits from treatments that are easier to self-administer at home.”

This, he says, is particularly true as a result of the pandemic. “Self-injection products will play an increasingly valuable role in driving compliance, protecting high-risk patients, and reducing the need for clinic-based treatment.”

ApiJect: Responding to Demand for Equity & Supply Chain Shortages

Global demand is rising for equi­table access to medicine, including in­jectables. Self-injection is already standard for insulin, many migraine drugs, and biologics. ApiJect is devel­oping products responsive to this de­mand, such as a scalable, low-cost, simple-to-use injection system that can potentially enable many patients to self-inject prescription medicines with minimal training, explains Dawn Carl­son, Senior Director of Program Man­agement at ApiJect.

“ApiJect’s focus includes develop­ing a new generation of simple, easily manufactured, prefilled syringes,” says Marc Koska, ApiJect’s Founder and Head of R&D. “We’re seeking both to enable high-speed, high-vol­ume drug or vaccine delivery in the ur­gency of the pandemic, and to help solve the problem of how to inject populations in low- and middle-in­come countries.”

The ApiJect Prefilled Injector, which, as this article went to press, has not been approved by the FDA, is a single-unit dose, soft plastic device. It is pressure-activated rather than in­corporating traditional barrel-and-plunger features. “We’re developing a broad platform enabling rapid scale-up for many types of injectable appli­cations,” says Ms. Carlson. “Our targeted user naturally depends on the specific drug that is packaged in the device.”

By designing a prefilled syringe that employs Blow-Fill-Seal (BFS) tech­nology, Mr. Koska says ApiJect expects to offer advantages of safety, speed, and reliable aseptic filling at prices that are highly economical and com­petitive with disposable syringes and multi-dose glass vials.

“BFS frees drug packaging from dependency on the supply chain used for glass vials, rubber stoppers, metal crimps, and other traditional syringe and vial components,” says Ms. Carl­son. “Our injector only requires plastic resin and an intramuscular needle. We plan to be our own needle sup­plier. BFS is well-established technol­ogy, widely recognized as inherently safe and effective.”

“Ever since the COVID-19 crisis began, pharmaceutical companies have been struggling with global “just-in-time” supply chains for glass vials and syringes,” explains Mr. Koska. “These supply chains are highly vul­nerable to disruptions that range from raw materials shortages to fill-finish capacity limits and even government export bans.”

Ms. Carlson adds: “The ApiJect platform uses BFS to offer pharmaceu­tical companies an alternative to tra­ditional supply chains. Our platform enables massive production scale-up on short notice; reliable aseptic filling; and much-reduced raw materials re­quirements. In addition, ApiJect Pre­filled Injectors combine the advantages of prefilled formats with the economy of multi-dose vials and disposable syringes.”

DALI Medical Devices: Self- Injection Features in One Device

One of the most important take­aways from the COVID-19 pandemic has been the search for ways to re­duce the burden and pressure on hos­pitals. To make this happen, self-injection treatments should be available for the home environment, says Ziv Cahani, Vice President Busi­ness Development and Marketing for DALI Medical Devices.

He says demand for DALI’s SAN® product family of self-injection devices was booming this past year. The SANs offer features that directly address the patients’ needs:

• Automatic needle insertion to the correct depth (SC/IM), so the pa­tient doesn’t need to worry if the needle wasn’t inserted into the right depth or require assistance from a nurse or other health care profes­sional.
• Automatic passive needle sharps protection against needlestick in­juries.
• Hidden needle before and after in­jection for patients who suffer from needle phobia.
• Manual control of injection speed to help the patient control the pain level.

“With this one-of-a-kind combi­nation of features, SAN-L not only meets the needs of a range of patient needs, but guarantees that the entire injection treatment is more comfort­able and that the medications are de­livered safely and securely,” he says.

Mr. Cahani adds that more drugs (mainly biologics and biosimilars) are being developed for subcutaneous in­jection. Many of these have different physical and chemical parameters (e.g., viscosity), so there is a need to customize the SAN product design ac­cordingly (e.g., adapt to different-sized needles). The SAN self-injection device’s needles range is between 18 and 29 gauge.

As an example of how SAN can be adopted and adapted, one pharma company’s commercial team sought a unique device to include one of its drug’s self-injection kit. The drug was in a prefilled syringe. “The team approached DALI because it was look­ing for a highly differentiated product, one that required special features to meet the specific design and injection requirements of the needle,” says Mr. Cahani. “And, of course, too, they wanted to offer a solution that patients would like.”

He adds that SAN-L is the culmi­nation of all necessary self-injection features in one product design.

Datwyler: Cartridge Plungers Feature Rubber Coatings for Improved Drug Compatibility

The development of an injectable drug-device combination is a complex process that requires substantial in­vestment of resources and money to achieve desired and successful out­comes. A variety of self-injection de­vice platforms are available that offer benefits like shorter time-to-clinic, lower up-front investments, and lower project risks.

For example, on-body injector de­vices, also known as large-volume in­jectors or wearable devices, are on the rise. These devices can be a good choice for the delivery of larger vol­umes of highly viscous biological drugs given the even and controlled pressure profile they can offer, ex­plains Carina van Eester, Global Prod­uct Leader, Prefilled Syringes and Cartridges at Datwyler. Various device companies develop platform devices that can handle volumes up to 20mL, most of which make use of prefilled cartridges. Cartridges utilize estab­lished materials, components, and fill­ing processes. Datwyler’s portfolio includes larger-sized plungers for car­tridge barrels up to an internal diam­eter of 23.85mm.

In many cases, the drugs that go into these self-injection devices are bi­ological drugs that require a coated rubber closure. Datwyler offers Omni­Flex^TM coated serum stoppers and NeoFlex^TM plungers that have the same composition and are made out of the FM457 compound with a fluo­ropolymer coating on top. The com­ponents are fully coated so the drug runs no risk of touching uncoated rub­ber, says Ms. Eester. “The benefit of using the same rubber formulation and coating at both ends of the drug product is reduced complexity during extractable and leachable studies,” she says. “Datwyler’s coated solutions provide drug compatibility, functional­ity, and machineability. The fluo­ropolymer spray coating provides a barrier to extractables and leachables while ensuring smooth delivery in the field.”

The NeoFlex plungers and Omni­Flex stoppers are 100-percent camera inspected and meet demand for qual­ity and performance for highly sensi­tive, large-molecule drugs. To complete the closure, Datwyler offers a range of aluminum seals that are produced, controlled, and tested under stringent conditions.

Duoject Medical Systems: Responding to Changing Healthcare Needs

In recent months, Duoject Medical Systems has been working on self-contained injection devices – devices that don’t require additional packag­ing. The Maverick emergency auto- injector is a good example of this. It does not require any additional pro­tective casing to contain the device as the patient carries it on them con­stantly, explains William Fortina, Busi­ness Development Director, Duoject Medical Systems.

“This is a crucial advantage for someone facing a life-threating event such as an anaphylactic shock; it al­lows for completing the injection faster.” He adds that developing de­vices without extra packaging or cas­ing can also be an eco-friendly argument.

Duoject has also focused efforts on user-step reduction, which in the context of self-administration and at-home care, makes the device more patient friendly. “This in turn increases the likelihood of patient adherence and reduces chances of user errors,” says Mr. Fortina.

Some of Duoject’s pharma clients are increasingly interested in platform devices that allow pharmaceutical labs to reuse a device platform for multiple applications with minimal customization required. “If a novel technology is necessary, Duoject ap­plies its robust design process,” he continues. “When designing new drug reconstitution and injection devices, we put an emphasis on early iterative prototyping and human factors testing to find out friction points and flaws early on, and eliminate them from the design before moving on to the actual device development phase.”

Finally, Duoject continues devel­oping reconstitution systems for lyophilized drugs. He says that differ­ent systems allow clients to combine different primary containers: vial-to-vial reconstitution (Helium device), sy­ringe-to-vial (Xenon and EZ-Link adaptors), and vial-to-cartridge (Pen­Prep EVO). These reconstitution sys­tems are helpful as pharma companies develop more complex molecules and biologics, which are sometimes only stable in lyo form.

Enable Injections: Flexible & Convenient Care

The healthcare system, post-COVID, will demand flexible drug de­livery options. Enable Injections has spent time with key opinion leaders to better understand the shifting patient and provider needs throughout the COVID-19 pandemic. The need to re­duce patient exposure to viruses and free up healthcare resources has driven unprecedented innovation in drug delivery. As a result, patients, providers, and healthcare systems are embracing more flexible care.

The enFuse^® is suited for flexible care, says Matt Huddleston, Chief Technology Officer and Executive Vice President of Business Development at Enable. “And our flexible delivery model, EnywhereCare^TM with enFuse, allows a range of delivery options for patients and providers, from in-clinic to at-home self-administration of ther­apeutics.”

As patients transition to the home in a flexible care model, maintaining the same quality of care will require delivery technology to provide solu­tions to connect with their physicians, other patients, training, reminders, and confirmation of delivery success. One of the many ways in which En­able is working to maintain this quality of care is through the development of the Smart enFuse, which supports next-generation patient/healthcare provider connections and enables flexibility in the site of care, explains Jennifer Estep, Senior Director, Mar­keting & Strategy at Enable.

In the past year, Enable has fo­cused on the validation and clinical success of the enFuse delivery solu­tion. Two clinical trials were recently completed, and another trial is in progress. “These clinical trials demon­strate our ability to subcutaneously (SC) deliver large volumes – 25mL and more – without the use of chemi­cal additives or enhancers,” says Mr. Huddleston. “For patients currently re­ceiving care with a large-volume sub­cutaneous delivery device at home on their own, 100% of these patients re­ported they prefer the enFuse over the current alternative SC method of de­livery. Our goal is to enable conven­ience for the patient, with the goal of making a positive difference in patient compliance.”

Flex: Human Factors Engineering Simplifies the Complex

In this highly competitive industry, the most successful companies have established rapid product develop­ment cycles that incorporate robust us­ability studies. By putting people at the center of medical device design strat­egy, human factors engineering (HFE) can drive products that simplify the user experience.

“With a deep understanding of user needs and expectations, HFE ex­perts can be involved at each step of the development process, from early user needs definition through summa­tive usability validation, to ensure that the disparate needs of distinct user groups are met,” says Jennifer Sam­proni, Chief Technology Officer of Health Solutions at Flex. “The resulting product may be more complex while advantageously being perceived as more user-friendly.”

At Flex, human factors and engi­neering teams have integrated multi­ple sensors into novel autoinjectors that are specifically designed to ad­minister biologics, she explains. “This technology can vastly improve user compliance by simplifying the number of factors the user must track.”

Accurate temperature sensing is also of utmost importance because many biologics require cold chain storage. The automated injector can verify the temperature of the drug and either prevent the injection from start­ing, warm up the drug via active heat­ing or adjust the injection force. Rotary encoder and force sensors can be used together to arm the motor driv­ing unit with more accurate data to support different injection profiles and deliver a consistent patient experience. “In each of these examples, smarter, more complex systems actually sim­plify the workflow and user experi­ence,” she says.

Haselmeier GmbH: Smart Drug Delivery in Clinical Trials

Big tech is delivering leading tech­nologies supporting the paradigm shift in healthcare, not only with the collection of patients’ data but also how they make use of that data. As a result, wearables and connected de­vices are increasingly finding their way into clinical trials. For example, John­son & Johnson’s Heartline study is using data from the Apple Watch to support earlier detection of arterial fibrillation in patients (www.heartline.com). This study, initi­ated in 2020, seeks to enroll 150,000 patients.

The future of clinical trials is be­coming more reliant on connected medical devices: Collecting data at the point of care, reducing the need for costly patient visits and cumber­some manual data acquisition.

Therefore, Haselmeier developed the D-Flex^TM Ecosystem, a connected drug delivery solution that can be in­tegrated into mobile solutions, collect­ing injection data at the point of care. The system is based on a proven tech­nology, which was successfully used in a clinical trial with 75 patients com­pleted in July 2018, says Frank Leipold, Business Development Digital Solutions, Haselmeier. The learnings from that trial translated into the new D-Flex Ecosystem (https://doi.org/ 10.2337/dc18-1631).

The D-Flex Ecosystem consists of the disposable D-Flex^TM injection pen and the connected cap, which re­places the standard cap of the pen. The connected cap tracks injection dose, temperature, and time up to 1,000 injection events. It securely transfers data in real-time to the Haselmeier patient app and cloud or any other pre-existing data manage­ment system via Bluetooth Low Energy. As an option, customers can choose to have the data stored and forwarded to the data management system at a later date. This eliminates the need for a patient mobile phone.

The D-Flex injection pen is at the heart of this connected solution, says Terry O’Hagan, Managing Director, Haselmeier Inc. “D-Flex is a complete platform allowing for simplified adap­tion of specific injection dose volumes by changing only one component. This saves time and cost during clini­cal testing, especially with dose rang­ing studies, because it allows using the same pen for all clinical testing and product launch, eliminating the need for additional equivalence/user stud­ies.”

The connected cap identifies the actual dose delivered by the pen by comparing the position of the plunger before and after each injection. Six LEDs emit an infrared (IR) signal that is altered by the plunger position. Six­teen IR sensors then detect the incom­ing signal. The delta between the two states identifies the relative movement of the plunger, delivering the actual expelled dose during an injection. This way, the cap calculates and displays the remaining volume in the cartridge.

Kahle Automation: Custom Equipment for Various Injection Devices

According to Julie Logothetis, President of Kahle Automation, re­gardless of design and safety ad­vances, the needle and syringe play an integral role in drug delivery from low dead space designs that maximize the dosing of the COVID-19 vaccine to auto-retractable syringes and unique new injection device designs that provide for economic self-con­tained devices that allow vaccine in­jections that can be easily distributed worldwide and meet single-use injec­tion requirements.

Kahle Automation has been de­signing and building custom high-speed automation equipment for multiple injection device projects, pro­viding solutions that assemble devices from 10ppm to 700ppm with com­pletely validated manufacturing and packaging systems to meet the de­mands of the industry. Current proj­ects include micro-injection devices for ocular injections, low-dead-space safety needles and syringes, auto-re­tractable syringes that self-destruct once the injection is delivered, and glass syringes that allow for the drug and the delivery system to be com­bined into one device.

Kymanox: Accelerating Device Development & Delivery

While Kymanox is not a device manufacturer, the company provides drug and device manufacturers with end-to-end solutions to accelerate de­vice development and delivery. “Right First Time” is how Kymanox ap­proaches product and process devel­opment and engineering, says Michael Denzer, Vice President of Technical Solutions, Kymanox. “Our integrated solutions, which include project management, quality assur­ance, regulatory affairs, clinical and medical affairs, and digital transfor­mation, support and drive our clients’ device development projects to deliver products to patients with optimized safety, quality, efficacy, and accessibil­ity.”

Kymanox has worked on a variety of handheld and wearable injection devices including single-use and multi-use cartridge-based devices. The therapeutic applications include critical care and emergency use as well as chronic disease management. The targeted users range from adoles­cents to seniors and include patients who have to prepare the treatment themselves.

“For sensitive biologics, patients must reconstitute the drug and, at times, adjust the injectable volume for their body weight,” says Mr. Denzer. “These activities add confusion and anxiety to the patient. At Kymanox, we strive to simplify this process as much as possible.”

SCHOTT: Syringes Aimed at Improved Compliance

Patient compliance relies on quick, pain-free injection experiences. Optimized for integration with autoin­jectors, SCHOTT’s syriQ^® BioPure pre­filled glass syringe underpins the self-injection experience through its in­fluence on injection force and dura­tion. With dimensional tolerances that go beyond ISO specifications, syriQ BioPure supports consistent injection times of less than 10 seconds. “De­signed for sensitive biologics, with ultra-low tungsten residual levels, low particulate, and low homogeneous sil­icone levels, syriQ BioPure PFS sup­ports the ideal patient experience,” says Michelle Deutsch, Senior Global Product Manager, Glass Syringes, SCHOTT.

SCHOTT’s primary packaging works with various industry device so­lutions, such as the family of Ypso­Mate^® 1mL and 2.25mL autoinjectors from Ypsomed. The YpsoMate autoin­jector is an automated disposable in­jection device for 1mL-long prefilled syringes. The device is triggered by push-on-skin activation. Ypsomed re­sponds to the challenge of adherence and therapy management by provid­ing the SmartPilot^TM for YpsoMate, a reusable add-on that transforms Yp­soMate into a fully connected smart product system.

In addition to syriQ BioPure glass PFS, SCHOTT TOPPAC^® syringes are suitable containers to be used inside injection devices. SCHOTT TOPPAC offers customers the possibility to indi­vidualize Cyclic Olefin Copolymer (COC) containers for self-injection de­livery to match their specific needs. “The flexibility and precision of injec­tion molding the COC material with their low particulate, as well as the low silicone levels, provide an especially promising containment option in the biologics space,” says Tom van Ginneken, Senior Global Product Man­ager Polymer Solutions at SCHOTT.

Sonceboz: Ease of Use & Implementation Are Critical

Sonceboz is focused on devices that provide a balance between ease of use and ease of implementation. “While the first is a requirement by regulatory bodies, the latter should not be put out of focus,” says Thomas Mayer, Business Unit Manager, Sonce­boz. “A number of device programs fail because they are too complex to integrate into existing and proven pharma processes.”

As an example, he points to pri­mary drug containers. “Primary pack­aging is key in protecting the integrity and safety of a drug product and bar­riers for change are high. For this rea­son, we focus on compatibility with standard vials in our lead device, the LVI-P20.” While the lead device is built for compatibility with any vial con­tainer, a later lifecycle management device, such as the LVI-P20, is focused on maximum ease of use with reduced use-steps.

Mayer explains that the Sonceboz devices deliver large volumes, up to 20mL and more, in a compact pack­age and are flexible as well. “We work with existing and proven containers, we cater to complex use cases involv­ing multiple containers, and offer an innovative business model that allows our partners to innovate based on our core architecture composed of the GentleTouchTM fluid path and pump, as well as WhisperDrive brushless mo­tors.”

West Pharmaceutical Services, Inc.: Digitally Enabled Product Strategy

“West believes the solution lies in simplifying the journey for the patient, physician, and pharmaceutical com­pany,” says Lawton E. Laurence, Sen­ior Director, Applied Research & Tech­nology for West.

To that end, the SmartDose^® 10 Injector has seen increasing customer demand driven by its ease of use, flex­ible performance, and the company’s experience with commercializing wearable injectors, he continues. “In comparison to burdening oncology clinics with developing bespoke pro­grams to safely administer drug ther­apies at home, a drug approved for use with our SmartDose 10 injector means those requirements are ad­dressed through the system’s patient­centric design and validated through rigorous human factors studies.”

Mr. Laurence says one concern West has heard from oncologists is around patient adherence. “For can­cer patients, a missed or delayed dose can have life-changing ramifications that don’t necessarily exist with other diseases. Based on this therapeutic specific insight, we are developing a solution that would add remote dose capture and an injection metric data stream without sacrificing the user ex­perience that has been so well re­ceived. The result is our concept development effort for the connected SmartDose 10 injector, which will leverage our IoT technology platform and the West digital ecosystem.“

With the advent of this system, the patient care team will receive critical information regarding the patient’s adherence and experience. When the injection is successful, confirmation will be registered in real time along with any qualitative experiential data the patient records in an automated post-injection report. In the event a dose is overdue, an escalating series of interventions will be triggered. Start­ing with a text message reminder and potentially progressing up to a home visit, the intervention protocol will be customized based on the therapy’s risk profile. “We believe a digitally en­abled combination product strategy produces the best possible experience for patients, helps accelerate therapy availability where it’s needed, and lowers the overall cost to the health­care system,” he says.

Ypsomed: Smart, Reusable Prefilled Pens

Smarter injection devices are part of the current innovation life cycle and will be an integral part of digital ther­apy management ecosystems. The complexity of the smart componentry depends on the type of therapy. For example, Ypsomed sees demand for smart, reusable, prefilled pens for short-acting insulin to treating Type 1 diabetes in combination with continu­ous glucose monitoring and dedicated apps. This provides patients with a real-time bolus calculator and HCPs with an overview of blood-sugar levels over time, explains Ian Thompson, Vice President Business Development, Ypsomed Delivery Systems.

“For prefilled autoinjectors, there is always the question of what level of smartness works best for a particular therapy,” says Mr. Thompson. “A con­nected, reusable add-on provides ad­vanced patient guidance and detailed injection logging, but adds user steps, which may be best suited to certain therapies where patient behavior is critical and closely monitored. As many patients receive support from therapy apps for their conditions, we also see a demand for prefilled de­vices with built-in electronics that will provide basic device guidance and in­jection logging.”

YpsoDose is a cartridge-based patch injector that is prefilled, pre­assembled, and electromechanical in this device category. For infrequent large injections of antibody therapies currently administered intravenously, Mr. Thompson expects YpsoDose to provide a safe and easy-to-use format for the hospital/clinical environment and for specialist therapies in the home setting. “In the hospital setting, YpsoDose will free up valuable infu­sion infrastructure, reduce the risk of dosing errors, and save time for healthcare professionals treating pa­tients with life-saving oncology drugs,” he says. YpsoDose is currently being industrialized for use in clinical trials.

“Patient compliance is improved by simplifying the user handling steps to “patch and inject,” and providing audible and visual feedback, which has been confirmed in comparative human factors testing,” says Mr. Thompson.

Congruence Medical Solutions: Pioneering Flexible Dosing Solutions

Congruence Medical Solutions is developing a number of drug delivery device platforms aimed at applica­tions involving microliter dosing, maximizing injection flexibility, and minimizing drug waste. Emerging needs of injectable drugs currently in development require more flexibility than most injection device platforms can currently provide, explains Phil Green, PhD, Head of Commercial and Business Development at Con­gruence. Several variables inform de­velopment and selection of a device platforms, including injection volume, formulation viscosity, regulatory com­pliance, needle safety, cost, human factors, and more.

“These afford flexibility for a phar­maceutical partner across the entire portfolio of drugs irrespective of stage of clinical development,” says Dr. Green. “Development of the Congru­ence Flexible Dosing Syringe (FDS) platform aims to provide this flexibility to pharmaceutical companies.”

Some potent immunotherapeutic agents in oncology require a range of dose volumes based on patient weight or other factors. Also, drugs with pe­diatric indications may require signifi­cantly different dose volume than for adults. The maximum dose for most pen injectors, which allows variable dosing, is 1mL or less. The FDS has been developed to accommodate a wide range or injection volumes (50 microliters through 2.25mL). “Flexibil­ity in injection volume also may be an important capability for dose ranging studies during clinical trials; minimiz­ing re-formulation costs for a clinical stage drug,” Dr. Green says.

While water-like viscosity is prefer­able from an injection system stand­point, increasingly formulations are getting more viscous. The FDS plat­form accommodates increasing vis­cous formulations, and has demonstrated ability to inject formula­tions as high as 1500cP with standard prefilled syringes.

“It is beneficial for a device plat­form to afford greater flexibility neces­sary during clinical drug development, but also bridge to a commercial em­bodiment with minor modifications. The flexibility afforded by the Congruence FDS can help bridge the clinical em­bodiment of the injection device with corresponding commercial embodi­ment. For example, a manual FDS in­jection device could be used in clinical trials, but an FDS autoinjector could be the commercial embodiment,” he says. The Congruence FDS can be made available in both a manual injection and an autoinjector format.

References

1. Injectable Drug Delivery Devices Global Market Report 2021: COVID-19 Growth and Change to 2030, ResearchandMarkets.com, March 21, 2021, https://www.businesswire.com/news/home/20210521005182/en/Global-Injectable-Drug-Delivery-Devices-Market-Report-2021-Market-is-Expected-to-Reach-25.79-Billion-in-2025—COVID-19-Impacts-Growth-and-Changes-to-2030—ResearchAndMarkets.com.
2. Drug Delivery Devices Global Market Report 2021: COVID-19 Implications and Growth to 2030, ResearchAndMarkets, Aug. 6, 2021,https://www.businesswire.com/news/home/20210806005310/en/Drug-Delivery-Devices-Global-Markets-Report-2021-Oral-Injectable-Topical-Ocular-Pulmonary-Nasal-Transmusocal-Im­plantables—ResearchAndMar­kets.com.