Combination products require more than pairing a drug with a delivery system. Their development demands coordinated planning across pharmaceutical, device, quality, regulatory, and clinical functions; often much earlier than organizations anticipate.
While many companies recognize the importance of incorporating a device, it is still frequently introduced too late. This delay can create downstream challenges in design controls, human factors, verification readiness, quality systems, and regulatory timelines.
For many organizations, device integration begins only after clinical data supports advancing a drug program. At that point, teams move quickly to identify a delivery system and prepare for clinical use. However, device development introduces additional requirements that must be addressed earlier and in parallel with the drug program.
Successful combination product development depends on early alignment around the route of administration, target product profile, device strategy, and quality system readiness. Without this, the device risks being treated as an accessory rather than a regulated constituent part.
When Should the Device Team Be Brought In?
Device engagement should begin as soon as the route of administration and target product profile are defined, typically around late Phase 1 or early Phase 2, and well before IND submission.
The activities required to support device integration are often underestimated. These include feasibility work, platform evaluation, quality system updates, human factors planning, and compliance with 21 CFR Part 4.
A realistic timeline accounts for approximately 14–18 months prior to IND or clinical trial start to complete these foundational activities. Without this lead time, teams are forced to execute multiple critical workstreams in parallel under compressed timelines.
A High-Level Device Development Roadmap
Device development can be viewed across three key phases:
- Feasibility Phase
This phase focuses on evaluating device platforms, primary container selection, and early usability and technical assessments. It also includes establishing the quality framework needed to operate under design controls. - Clinical Development Phase
Once a platform is selected, development proceeds under design controls with formal risk management, requirements definition, and iterative design activities to support clinical use. - Commercial and Validation Phase
This phase includes design transfer, validation planning, and preparation for commercial launch, ensuring manufacturing, packaging, and quality systems are ready for scale.
Risks of Late Device Integration
Introducing the device too late creates several risks:
- Clinical configuration may not match the commercial product, requiring bridging studies
- Human factors validation may be delayed, impacting submission timelines
- Drug-device incompatibilities (e.g., injection force, dose accuracy) may surface late
- Quality systems may lack design controls or combination product readiness
These issues can delay clinical trials, impact submissions, and in some cases require redesign after pivotal studies.
Common Challenges
A common issue is delaying quality system integration. While early updates may be manageable, later-stage gaps, particularly in post-market processes and compliance with 21 CFR Part 4, become significantly more complex to address under time pressure.
Design verification is also frequently underestimated. Verification readiness depends on defined requirements, validated test methods, and robust protocols.
Test method validation, in particular, is a common source of delay. Even when working with established device platforms, failures or gaps can add months of rework per method.
Key Considerations for Delivery System Selection
Selecting a delivery system requires structured input across multiple domains. Four key considerations include:
- Design Controls and Regulatory Requirements
The device must be developed under design controls with alignment to combination product regulations. - Human Factors Strategy
When applicable, formative work should occur before clinical use, or at a minimum be assessed, with clear understanding of the intended users and use environments. - Technical Compatibility
Drug characteristics such as viscosity, dose volume, and stability must align with device capabilities. - Manufacturing Readiness
Clinical supply requires established assembly, packaging, and supplier coordination, including lead times for device components.
Common Mistakes
Companies often:
- Underestimate the time required to introduce a device
- Delay implementation of design controls
- Skip early human factors work
- Assume platform devices will always be a “plug-and-play” solution
- Operate in silos across device, regulatory, and clinical teams
Even with established platforms, moving outside validated conditions (e.g., new users, higher volumes, different formulations) introduces new risks.
The Impact of Organizational Silos
A major challenge in combination product development is the disconnect between pharmaceutical and device teams. These groups often operate with different processes, timelines, and terminology.
Without alignment, this can lead to inefficiencies, miscommunication, and delays. In many cases, teams lack visibility into each other’s requirements, which creates friction and slows execution.
The Role of Cross-Functional Training
Cross-functional training is critical to improving alignment.
Pharmaceutical teams must understand design controls, risk management, and verification requirements, while device teams must understand clinical strategy and drug development constraints.
This shared understanding helps teams align on timelines, expectations, and decision-making, reducing delays, and improving overall execution.
Platform vs. Bespoke Device Strategy
Most companies adopt platform devices to reduce technical and regulatory risk. These platforms offer established design, manufacturing, and usability data.
However, bespoke devices may be appropriate when:
- The drug has unique technical requirements
- A differentiated user experience is needed
- The device provides competitive advantage
That said, bespoke solutions introduce greater complexity, cost, and timeline risk. The more novel the design, the higher the exposure to technical and regulatory uncertainty.
Conclusion
Combination product development requires early and deliberate integration of device strategy into the broader programs.
Engaging device teams early, aligning cross-functional stakeholders, and implementing design controls upfront can help organizations avoid common pitfalls, reduce delays, and improve submission readiness.
Ultimately, success depends on treating the device as a fully integrated and regulated component—not a late-stage addition.
At Ventura Solutions, we specialize in helping medical device and combination product companies navigate complex challenges throughout all stages of development. Whether you need end-to-end support with an integrated device team, quality or regulatory consulting, assistance with DHF remediation, additional staffing needs, employee training, or more; our team of experts are ready to help. Contact us today.
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