An evaluation unit for the clinical version of the MACH-1 vaccine delivery platform.

In the complex landscape of medical innovation, developing combination products—devices that incorporate a drug or biologic component—presents a unique set of challenges that demand more than technical brilliance. It requires a delicate orchestration of expertise, resources, and vision across multiple disciplines. At February's MD&M West 2025 in Anaheim, I joined Kristyn Aalto, CEO of Orlance Inc., to share our journey in developing the groundbreaking MACH-1™ system—a needle-free, pneumatic delivery platform for DNA and RNA vaccines.

Kristyn Aalto, CEO of Orlance, speaking at MD&M 2025 Conference.

Our presentation, "Bridging the Gap: Strategies for Advancing Complex Medtech Systems to Clinical Testing," offered a rare glimpse into how resource-constrained innovators can navigate the complex regulatory and development pathway of combination products. The insights shared revealed a blueprint for success that extends far beyond traditional medical device development.

Legacy Tool

The pre-clinical research tool design that has supported Dr. Fuller’s studies and data collection. This unit is highly functional for users who have deep familiarity with the design and their testing objectives. However, it does not include thorough consideration for the use case of clinical research.

Clinical Use Case

While this version of the technology by Pfizer did not make it to market, this illustrates a potential use case where a clinician delivers a dose to patient’s skin. Our objective was to create a new design for the research tool that would enable dosing in clinical research settings.

The Scale Dilemma: When Biologic and Device Development Collide

One of the most striking revelations from our presentation was the fundamentally different scale and nature of biologic development compared to medical device development. As Kristyn Aalto explained, combination products face a unique challenge:

"Biologic combination products where EVERYTHING is novel equals regulatory plus design challenges. The drug formulation design is dependent upon the delivery technology, and nothing is off-the-shelf or already cleared or approved." - Kristyn Aalto, CEO of Orlance

This reality creates a development pathway that follows the biologic regulatory route—a far more extensive and costly journey than the typical medical device process. While a traditional medical device might reach market within 2-3 years via a 510(k) pathway, a combination product following the IND (Investigational New Drug) and BLA (Biologics License Application) route faces a multi-phased clinical trial process that can stretch across a decade and cost hundreds of millions of dollars. Figure 1 provides a graphical representation of this disparity.

Relative time and cost scale for medical device projects (blue) vs. biologic projects (orange).

For resource-constrained teams, this means making strategic choices about where to invest limited resources. As Aalto emphasized:

“With lean, highly specific funding that turns on and off, we’ve had to generate outsized spark and buy-in—often while being too early-stage for most CDMOs. That’s meant building just enough of a quality foundation, including our QMS, and preserving continuity in the team to avoid retraining or restarting every time the program ramps up again.” - Kristyn Aalto, CEO of Orlance

The Power of Collaborative Innovation Ecosystems

The story of the MACH-1 system exemplifies how the right innovation ecosystem can make seemingly impossible projects viable. The Seattle-based partnership between Orlance and Product Creation Studio leveraged a rich network of expertise from the University of Washington, where Dr. Deb Fuller was continuing her pioneering work in novel vaccine and vaccine delivery technology.

Dr. Deborah Fuller holding the legacy delivery system. Deb and team study viral pathogenesis in non-human primate models, with a focus on developing novel antivirals, vaccines, and immunotherapies for SARS-CoV-2, HIV, influenza, hepatitis B, Zika virus, and Valley Fever.

Rather than building an extensive in-house engineering team that would be difficult to sustain with intermittent grant funding, Orlance adopted a strategic approach—using Product Creation Studio as their "on-demand" engineering team. This arrangement provided the flexibility and expertise needed while allowing Orlance to focus on their core scientific objectives.

A representation of the collaboration between academic research, spin-out company, and strategic CDMO (PCS).

Aalto described this partnership as essential to their progress:

"Clear communication of project pace and timing contingencies, and finding a CDMO resilient enough to weather start/stop gaps while maintaining focus and continuity was critical to our success." - Kristyn Aalto, CEO of Orlance

The co-location of both companies in Seattle's biotech corridor facilitated quick collaboration, problem-solving sessions, and shared equipment usage. This ecosystem approach created a multiplier effect, where the combined expertise became greater than the sum of its parts.

Strategic Prioritization: Engineering for Clinical Testing, Not Commercialization

Perhaps the most valuable lesson from the Orlance-PCS collaboration was our disciplined approach to prioritization. Developing a complex combination product requires making difficult trade-offs between what could be built versus what should be built at each stage.

"When developing a platform for clinical testing rather than immediate commercialization, it's essential to focus your engineering resources on the elements that directly impact clinical outcomes…" - Scott Thielman, CTO of PCS-

The goal isn't to create a perfect commercial product, but to build a reliable platform that can generate the data needed to validate your therapeutic approach. This philosophy manifested in several key engineering decisions that illustrate the strategic prioritization needed for clinical-stage development:

The Dose Management System: Non-Negotiable Innovation

The heart of the MACH-1 system's effectiveness lies in its dose management capabilities. This aspect demanded significant design attention and genuine innovation.

The dose management system was where we invested our deepest engineering resources. This multi-component assembly with high-pressure pneumatics and multi-dose capability was critical to the system's performance. We discovered early on that we needed a three-component system with a custom cassette mechanism that could precisely manage high-pressure gas flow. This wasn't an area where we could compromise.

The team created an elegant solution that enabled precise, reproducible dosing of the powdered vaccine—an essential requirement for clinical testing where consistency is paramount. This focus on the core functionality that directly impacted the therapeutic outcome exemplifies the strategic prioritization needed in resource-constrained environments.

The Valve System: Strategic Compromise

While the dose management system demanded innovation, other components allowed for pragmatic compromise. The valve system is a perfect example of this approach.

"We made a deliberate decision to utilize a legacy industrial valve that was significantly oversized for our final commercial vision," I explained. "It was a huge component that dominated the handpiece design, but it was a known quantity with established performance characteristics. Rather than spending precious resources optimizing valve size and weight, we accepted this compromise to focus on the elements that would directly impact clinical outcomes."

This decision meant the clinical prototype was larger and heavier than the eventual commercial device would be, but it eliminated a significant engineering challenge while maintaining the essential functionality needed for clinical testing.

A slide from the presentation showing the strategic compromises made to conserve deveopment resources

Circuit Design: Regulatory Pathway Awareness

Another strategic decision involved how we implemented the control system for the device.

We designed the circuit using digital logic components rather than microprocessor-based software. This allowed us to avoid the additional complexity of IEC 62304 compliance for medical device software at this stage of development, while still creating a deterministic system with precise timing and reliable performance.

This approach meant a more complex hardware design but eliminated the significant time and resource investment that software validation would have required. The team recognized that in the context of an IND submission for a combination product, the delivery platform serves primarily as a tool in the background—the regulatory focus would be on the biological component and the clinical outcomes.

For the MACH-1 system's first clinical prototype, we made strategic decisions to emphasize certain elements while deliberately de-emphasizing others:

Emphasized:

Physics—airflow profile, sealing, timing
Dose management
Reproducibility
Safety for use by a trained technician

De-emphasized:

COGS (Cost of Goods Sold)
Component optimization
Controller sophistication
Safety for general use in varied clinical settings

Aalto summarized this approach as "recognizing the need within the development pathway" and "prioritizing the right thing." By building specifically for the next milestone rather than attempting to solve all challenges simultaneously, the team made efficient use of limited resources.

Powering Healthcare Innovation Through Strategic NIH Funding

The Orlance story also highlights the critical role of NIH SBIR (Small Business Innovation Research) funding in advancing breakthrough healthcare technologies. In a funding environment that has become increasingly challenging for early-stage life science companies, NIH grants provide non-dilutive capital that allows companies to achieve key technical milestones.

Orlance leveraged approximately $13 million in NIH funding to advance their MACH-1 platform—work that might otherwise have been impossible in the current venture capital landscape, which often shies away from high-risk, long-timeline vaccine platforms.

The public health impact of this work extends far beyond a single product. Aalto emphasized the enabling technologies that MACH-1 could bring to healthcare globally:

"This platform enables shelf-stable DNA vaccines delivered at microgram doses through a needle-free system that targets the epidermis, allowing for rapid manufacturing response, multi-antigen payloads, and durable immune responses."

These capabilities could transform vaccine delivery in resource-limited settings, enable faster responses to emerging pathogens, and reduce barriers to immunization globally—outcomes that align perfectly with NIH's public health mission.

Keys to Success in Complex, Resource-Constrained Projects

For other organizations facing similar challenges with combination products or complex medical technologies, the Orlance-PCS collaboration offers valuable lessons:

Create the right partnership dynamics: Find partners with the appropriate scale, resilience, and commitment to weather the inevitable ups and downs of complex development programs. As Aalto noted, the "rightness of scale" is critical.
Build institutional knowledge: Develop deep understanding between teams, create buy-in to program merits, and foster frank communication about business relationship structures.
Maintain clear boundaries: Establish mutual commitment to IP protection, business development activities, and knowledge sharing boundaries from the outset.
Adapt to the biologic-led pathway: Recognize that combination products with a biologic primary mode of action follow a different regulatory and development path than traditional medical devices. This means designing specifically for clinical testing rather than immediate commercialization.
Prioritize ruthlessly: Focus on what's needed for the next milestone rather than attempting to solve all challenges simultaneously.

The Path Forward

The collaboration between Orlance and Product Creation Studio demonstrates how strategic partnerships can transform visionary concepts into clinically viable products, even with constrained resources and complex regulatory pathways. By recognizing the unique challenges of combination products, leveraging the strengths of their innovation ecosystem, and maintaining disciplined prioritization, they've created a pathway to potentially transform vaccine delivery worldwide.

As healthcare innovation grows increasingly complex and interdisciplinary, these collaborative models will become ever more vital to bringing breakthrough technologies from concept to clinical impact. The MACH-1 story offers a blueprint for navigating this challenging terrain—and ultimately delivering innovations that could transform patient care globally.

Reach out to learn more about how Product Creation Studio can support your combination product development journey. Contact us at info@productcreationstudio.com.

Complex Combination Products from Vision to Clinical Reality