5 Top-Of-Mind Drug Delivery Topics In 2024

By Fran DeGrazio, executive editor, Drug Delivery Leader

2024 was certainly an active year for the pharmaceutical and biopharmaceutical industry. It was especially so around activities driven by industry growth and by the associated challenges of delivering safer and more effective drugs – and more of them – to patients. As I watched and reflected on advances in drug and therapy delivery throughout 2024, five familiar challenges continually appeared as topics of focus and conversation at industry conferences, in peer interactions, and during industry group collaborations.

Those five top drug delivery challenges from 2024 are the following:

• Qualifying device suppliers for combination products
• Applying a ‘systems’ approach to combination product development
• Leveraging platform devices to achieve speed to market
• Keeping pace with increasing demands and higher doses in self-administration
• Achieving regulatory approvals for combination products

Drug Delivery Challenge #1: Qualifying Device Suppliers

In early 2024, the FDA issued a final rule amending the medical device current good manufacturing practice (CGMP) requirements under 21 CFR 820 to align more closely with the ISO 13485:2016 international consensus standard for medical device quality management systems. This change also applies to combination products. (Later in the year, we here at Drug Delivery Leader, hosted an online panel discussion of the implications of this new Quality Management System Regulation, or QMSR, and I followed up with an article on the topic.)

This regulation has raised the importance of various aspects of CGMP especially for those biopharma companies that historically were more familiar with drug GMPs but are now working to develop and market a combination product. One of the key areas where industry is seeing gaps that must be closed is in purchasing /supplier controls. Suppliers in this space must understand what their obligations are. Their obligations go beyond the foundational requirement of delivering high quality products to encompass collaborating with sponsor companies. That means providing knowledge and documentation such as risk management files and control strategies, and to do so openly and without hesitation. It is the pharma company/market authorization holder’s responsibility to demonstrate that a supplier meets the needs for the device being acquired. Frankly, If the supplier is not open to exchanging risk and controls information, then perhaps it should not be identified or qualified as a supplier of a device intended for a combination product. (Later in the year, I returned to the topic in an article on supplier controls.)

Drug Delivery Challenge #2: Embracing A Systems Approach

Increasing in momentum as the year progressed was the practice of thinking and working more cross-functionally in the development, manufacturing and marketing of combination products. Historically, biopharma organizations have been set up in functional silos. Unfortunately, the ensuing structural barriers are not especially conducive to building combination products from a true systems perspective.

Of course, organizations must understand and mitigate risks in every stage, at every level, and for each individual component, raw material, drug product, or device that ultimately becomes part of a commercialized combination product. Nonetheless, throughout the entirety of the development process, those pieces must be viewed and brought together as a comprehensive system. In fact, the areas of greatest risk are most likely to be revealed at the process or design points when individual pieces come together. Having experts from cross-functional roles and perspectives working together and helping each other understand all of that is critical to successful execution. (Revisit my take on organizing around product development from earlier in the year.)

Drug Delivery Challenge #3: Leveraging Platform Devices

Overwhelmingly industry is looking to accelerate development and approval processes. Leveraging platform devices seems to be the main way of trying to accomplish this. Many of us had hoped that the FDA draft guidance Platform Technology Designation Program for Drug Development issued in May 2024 would also provide some direction for devices. The current draft does not do this, and the general sense is that FDA may not follow up with specific guidance for platform devices. As I see it, however, FDA seems to be open to platform device concepts and suggests using the bridging guidance as providing a high-level methodology for leveraging platforms.

With or without specific guidance defining their efforts, nearly all major pharma companies are working on applying platform concepts to drive increased speed and efficiency in product development. For industry, one of the most significant challenges is that there must be a great deal of  time invested early in evaluating and building a design space around the platform to characterize it for future use. Only a management team with vision will effectively operationalize this kind of concept.

Drug Delivery Challenge #4: Enabling Self-Administration

Also increasing in volume in 2024 – in terms of both the drug delivery challenge and the conversations about it – was patient self-administration. Ever since the delivery challenges that emerged during the COVID-19 pandemic, there has been a push toward improving capabilities for getting treatments to patients in a home healthcare environment. Self-administration of both cancer drugs and non-cancer drugs is seen as a way to improve quality of life while lowering costs.

The technical driver is the need for greater dosing and higher biologic drug concentration. Numerous technical papers by various researchers have underscored the need to address the growth in high-volume subcutaneous injections in the pipeline and to understand what is technically feasible, as well as acceptable to patients, in this arena. In the past, there has been a lot of supposition; however, a quick review of the literature or a glance at the attendance at conferences over the past year confirms a tremendous, rapidly increasing interest. For instance, in October 2024, many presentations on the challenges of increased volume delivery via self-administration were shared at the PDA Universe of Prefilled Syringes and Injection Devices conference.

There is a tremendous amount of innovation in this area and one that will surely drive the future of combination products. Right now, the most common approaches leverage formulation enhancers or the use of devices that can deliver greater volumes over time, such as on-body injectors or infusers. The regulatory picture confirms this trend toward self-administration. Compared to prior years, 2024 saw more and varied on-body, injector-based combination products approved by the FDA.

Drug Delivery Challenge #5: Achieving Regulatory Success

Perhaps the most important challenge area for industry, ultimately, is how to successfully receive regulatory approval and get to market with effective combination products so as to  aid patients as quickly as is feasible.

With that obvious goal in mind, Industry actively seeks guidance on what to do from a regulatory standpoint and wants to proceed accordingly. A key challenge, though, stems from the FDA perspective that each combination product is unique. As a result of the agency’s recognition of variability across combination products, the expectation is that the best understanding of the product is held by the market applicant for that product. Acknowledgement of this reality, heard throughout the year, was consistently amplified during the  October 2024 AFDO/RAPS Combination Products Summit co-sponsored with FDA.

As things currently stand, regulators are not going to provide a standard checklist of activities and data that should be submitted every time in support of an application for a combination product. The expectation, instead, is that the applicant justifies the decisions and choices that are being made along the way of product development – no matter how numerous or varied – and not simply follow a standard, minimum checklist of activities. In doing so, the applicant should provide clearly supportive and defensible information.

Frankly, market applicants should put themselves in the regulators’ shoes and make sure that the submitted documents clearly convey not just “this is what we are doing” but also explain how and why decisions about those activities were made along the way. Simply providing reams of data for reviewers to pore through is not an advisable approach. Telling a practical and clear story is. (Regulatory considerations for combination products were also helpfully outlined in a videocast conversation with the FDA’s Barr Weiner that my colleague, Drug Delivery Leader Chief Editor Tom von Gunden, conducted in summer 2024.)

Yes, there are many moving pieces and challenges in the drug device combination product space, but it is an exciting area that will bring many benefits to the end user and patient.