Data-Driven Innovation Is Drug Delivery's Next Evolution

By Drug Delivery Leader Editorial Staff

Drug delivery devices and the regulations guiding their design, production, and use have evolved significantly over the years. As more complex treatments like cell and gene therapies (CGTs) intensify the need for novel drug delivery technologies and techniques, biopharma organizations and device suppliers are exploring tools to advance precision medicine.

To mitigate inherent risks like inconsistent dosing, user error, and low adoption due to complex usage procedures, technological innovation in delivery devices is best guided by lessons from the past, including user feedback and follow-on learnings from market data. Exploring a brief history of delivery devices through the lens of several different case studies can not only reveal the benefits and challenges of those designs, but can also inform pragmatic innovation toward the next generation of drug delivery devices.

Lessons Learned In Delivery Device Innovation And Regulation

Established efficacy still benefits from added convenience. Innovation in drug delivery systems usually is an iterative process. Nonetheless, the EpiPen® autoinjector was approved by the FDA for emergency treatment of allergic reactions in 1987 and has undergone few changes in its technological characteristics since. This is consequential because the EpiPen is an emergency use autoinjector. Post-market lifecycle management of similar products typically involves bolstering reliability, especially as regulations catch up — as they did in this case with the FDA’s April 2020 guidance, “Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA.”

Autoinjectors are among several delivery technologies approved decades ago that have not gone through a significant evolutionary cycle. In fact, while epinephrine formulated for use in an autoinjector is known to have stability limitations, demand for an alternative delivery system stemmed not from concerns about efficaciousness or safety, but from a desire to overcome the delivery system’s user-related limitations. Specifically, the needle delivery is invasive and is not ideal for pediatric patients or individuals with high skin-to-muscle distance (STMD). Additionally, the EpiPen autoinjector is a relatively large device to carry at all times.

The industry’s response was Neffy®, an epinephrine nasal spray approved by the FDA in August 2024. Like the EpiPen, Neffy provides emergency treatment of anaphylaxis, but it does so using a less invasive, needle-free delivery. As a result, the industry improved patient accessibility and convenience while also addressing some concerns about dose control and reliability. This example illustrates how a thorough understanding of user experience can help align a novel device’s target product profile (TPP) with patients’ stated desires for improvement.

Familiarity is a powerful patient motivator. While EpiPen® represents a therapy where one form factor dominated the space until an alternative was developed, Enbrel® (etanercept) is a case of multiple form factors offered to the market with varying levels of success. Patients typically take Enbrel® weekly or biweekly to treat various autoimmune conditions, many for the entirety of their lives. So, the drug has a relatively high patient burden and innovation has focused on improving patient accessibility and compliance.

Enbrel® is available in a single-dose vial form, a prefilled syringe, an autoinjector, and the AutoTouch®, a reusable autoinjector with both disposable and reusable components. The AutoTouch was developed to improve accessibility and compliance by helping people with dexterity issues better control injection speed. However, market data indicates the autoinjector and the prefilled syringe still dominate the space, indicating familiarity remains a powerful factor in patient preference.

Similarly, the SureClick® autoinjector and the Pushtronex® on-body infusor both were designed for self-administration of Repatha, a treatment to lower cholesterol. Even though Pushtronex®, approved by the FDA in July 2016, was among the first on-body systems of its kind, market penetration was sluggish and the device was discontinued in June 2024.

Because of Repatha’s necessary dose volume, the autoinjector requires two injections, so the rationale was that a single-injection, on-body device would be preferable to users. But sometimes, the technological leap between on-body delivery systems and the prior standard of technology is so significant that developers overlook patients’ preference for familiarity over simplicity, even in cases where multiple injections are necessary.

Thus, the amended question becomes, “What form of device will simplify, speed up, and/or provide greater precision for dosing in the most effective, familiar way?” Innovation that provides a clear answer also can be more appealing to payers and reimbursement frameworks. So, examine the patient population and the competitive landscape, and then decide if your innovation is actually primed to penetrate the market based on documented user habits and stated preferences.

Intuitive design expands patient and user access.  Originally offered as an intramuscular injection administered by a healthcare provider (HCP), the opioid antagonist Naloxone was approved as a non-prescription, over-the-counter (OTC) nasal spray in March 2023. So, accessibility expanded to laypeople for emergency use, and even now, development continues to improve formulation stability in injected forms.

Naloxone is a unique market case in that it does not require diagnosis, but the necessity to improve its delivery is another example of how consideration of public health impact can impact innovation decisions. As a product that must be operated by novice users, in emergency situations, with little to no training, this drug/device also reinforces the importance of not overengineering solutions.

Innovation Can Help Guide Regulation

Hypodermic needles and syringes came about in the late 1800s, predating many modern government regulatory systems and medical technology organizations. In the 1930s and 1940s, wartime necessity prompted the introduction of more prefilled syringes and early autoinjector kits. By the mid-1950s, glass and plastic disposable syringes were among the first delivery devices in mass production. Fast-forward a few decades, and innovation in autoinjector technology and needle safety began emerging more frequently in the 2000s.

Even with this continued evolution, ISO 11608-8 — an international standard that specifies requirements and test methods for needle-based systems — was not published until 2022, six years after the FDA’s first approval of an on-body infusion device in 2016. Novel technologies can help inform the policy and the framework through which they can and should be regulated, so it is critical that biopharma organizations and device suppliers work hand-in-hand with regulators as they design and test novel delivery systems. This approach is conducive to the creation of a more robust target product profile (TPP) for each device and enables innovators to collaborate with the agency to avoid or overcome potential regulatory challenges.

The Next Generation of Drug Delivery

The next generation of drug delivery will be increasingly complex as devices expand to manage not only traditional pharmaceuticals but also CGTs, vaccines, and other biologic products. Combined advanced targeted therapies (CATTs) — which embed a cell therapy product into, for example, an implantable scaffold or delivery device — also exist on the frontier of drug delivery. From a global perspective, OEMs and the industry must be mindful of the regulatory frameworks being developed, or to-be-developed, for these innovative technologies.

OEMs and their partners must scrutinize their rationales for what constitutes unmet/underserved medical need and understand what it will take to develop a product for that specific market — particularly if the marketplace is crowded. For example, the FDA has seen exponential growth in investigational submissions for nanotechnology or microfluidics-based delivery technologies targeting unmet or underserved needs. Additional goals for novel delivery device development currently include:

• Providing patients with greater at-home access to medicinal products and enabling more convenient dosing where technology innovation has seemingly stalled.
• Overcoming the current limitations of drug delivery systems, including poor dose accuracy and/or low patient tolerance. This challenge is exacerbated when working with therapies that require multiple doses, titration, or weight-based dose solutions limited by available technology.
• Improving advanced delivery reconstitution systems, used across a range of therapies, is of particular interest to developers. While significant innovation has taken place, few technologies have actually impacted the combination therapy market.
• Sustained release can be improved through closer collaboration between device and drug OEMs to characterize the medicinal product with delivery system materials in development, enhancing sustainability and product reliability. While device technology can affect controlled release rates, biological considerations, such as degradation rates in the physiological environment and even the markers or cues that trigger release rates, are more wide-ranging.
• Delivery systems increasingly feature Bluetooth connectivity and other digital solutions intended to help improve patient experience, data reporting, and/or user adherence. Development of such devices typically requires a web of partnership between the device OEM, one or more digital firms, and a pharmaceutical OEM handling the therapy’s medicinal elements.

Innovation Usually Is A Process, Not A Revelation

Determining how much of a departure from standard practice is possible before users reject a device is crucial. Moreover, every increase in device complexity adds new challenges to development, to regulatory navigation, and potentially to post-market device management. The regulatory strategy for a drug delivery device must consider the entire asset, not just its separate parts, and each development or manufacturing partner’s role must be explicitly defined.

In any scenario, the industry’s shared goal is to develop drug delivery products that help to either eradicate or better manage a particular disease state across various therapeutic areas. To accomplish this, the industry must evolve in its understanding of patients’ interactions and experiences with its products as it innovates, finding better ways to translate that information into a TPP. Delivery system OEMs also must embrace an even more collaborative relationship with regulators, providing the data needed to help them establish policy and precedents surrounding these technologies.

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