Combination Product Industry News & Guidance

Consider a combination product program that has navigated early development successfully. Design inputs established, verification testing underway, and a regulatory submission on the horizon. Then FDA issues a revised version of a foundational guidance document that redefines baseline expectations for how drug delivery performance is defined, verified, and maintained. What was considered a complete data package may now require meaningful rework. The submission timeline shifts. The conversation with leadership is difficult. For teams working on combination products today, one such signal deserves close attention, the pending update to the FDAs Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products, also commonly referred to as the EDDO Guidance.

EDDO: A Guidance, A Pending update

In 2024, FDA’s Office of Combination Products issued a draft guidance titled Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products, referred to across industry as “EDDO.” The guidance established a framework for identifying the drug delivery outputs that are essential for a given combination product, and for ensuring those outputs are verified during development and maintained through routine production. It was a meaningful step toward clearer FDA expectations in an area that had long relied on informal conventions and sponsor judgment.

According to FDA’s Office of the Chief Medical Officer (OCMO) 2026 Guidance Agenda, EDDO is listed as a Calendar Year 2026 priority for the Office of Combination Products. This means an updated draft or revised final version of the guidance could emerge within the year. OCMO and the Office of Combination Products (OCP) has been transparent that its agenda is aspirational, timing depends on available resources and shifting agency priorities, but the fact that EDDO appears on this list so soon after the original draft, is a signal worth tracking. Something is being actively worked on.

The scope of any revision remains unknown. FDA has not disclosed what aspects of the 2024 draft are under review, nor whether the update will represent a minor refinement or a more substantive rewrite. That ambiguity itself is relevant, because it means programs cannot scope their exposure until the document appears. What they can do is ensure their current program is well-positioned regardless of what changes.

The Absorption Problem

What makes this moment particularly relevant is that, despite broad awareness of the 2024 draft guidance, formal integration of its core principles into active development programs remains inconsistent across the industry. Familiarity with a guidance document and operational alignment to it are two different things. In practice, we continue to encounter programs that are still operating against legacy frameworks, focusing entirely on concepts like Primary Functions from the ISO 11608 series or similar predecessor constructs, under the assumption that historical precedent will carry sufficient weight with reviewers.

The identification step alone requires more rigor than many teams apply. It is not a matter of inheriting a supplier’s standard test battery or defaulting to outputs that were relevant for a prior product. EDDO asks sponsors to reason through which outputs are truly essential given the specific drug, device, and intended use, and to document that reasoning in a way that supports regulatory review. Teams that have not approached this with structured, risk-based thinking are often working from an incomplete foundation, even if their verification data looks robust on the surface.

Across the combination product programs our team supports, this gap appears consistently enough to be treated as an industry-wide pattern rather than an isolated oversight. It is particularly common in programs where device development has been led primarily by a pharmaceutical organization without deep device engineering experience, or where early device decisions were made before the EDDO framework was formally considered.

Where FDA Focus Is Sharpest: The Production Lifecycle

If there is one area where we see the most significant gaps (and where FDA review scrutiny tends to concentrate) it is not in development-phase verification. It is in how EDDOs are maintained throughout the production lifecycle.

Identifying EDDOs and verifying them during development is a necessary starting point. But the more demanding and often overlooked question is: how are those outputs controlled as a product moves into commercial manufacturing? Are the EDDOs embedded in the control strategy in a way that ensures routine production consistently delivers the drug delivery performance that was verified during development? Is there a clear, documented link between the essential outputs, the design controls that govern them, and the ongoing manufacturing controls that maintain them?

This is where FDA’s attention increasingly falls during review, and where many programs are most exposed. In practice, the control strategy often lags the development program. EDDOs are identified and verified, but the translation of those outputs into meaningful production controls (specifications, process parameters, incoming quality requirements) is incomplete or poorly documented. The result is a submission that can demonstrate development-phase performance but cannot demonstrate that the same performance will be reliably delivered at commercial scale, lot after lot.

This is also the area most likely to be sensitive to any guidance update. If FDA’s revised EDDO guidance sharpens expectations around control strategy integration, programs that have not already built this bridge will face meaningful remediation work.

De-Risking the Unknown Through Sound Engineering

The practical response to regulatory uncertainty is not to wait for the updated guidance before taking action. Programs built on sound engineering fundamentals, with explicit, risk-based rationale for EDDO identification and a clear thread from essential outputs through verification and into production controls are inherently more resilient to guidance evolution, regardless of what the update ultimately contains.

This means ensuring that:

• EDDO identification is documented as a deliberate, traceable decision tied into a formal Risk Management process and substantiated with specification limits which are aligned to your intended use — not an assumption inherited from a device supplier or a prior program.
• Verification data is organized to map clearly back to each identified essential output, so that a reviewer can follow the logic from requirement to evidence without inference.
• The control strategy reflects the essential outputs in a meaningful and technically robust way, not as a retrospective documentation exercise, but as an active part of how manufacturing performance is defined, specified, and monitored on an ongoing basis.
• Cross-functional alignment exists between device engineering, regulatory affairs, and pharmaceutical development. EDDO sits at the intersection of all three, and gaps in coordination tend to produce the exact data mismatches that generate information requests during review.

Teams that have built their programs this way tend to experience guidance updates as clarifications to assess, rather than requirements to scramble against. The structural work is already done. Teams that have not tend to find that a guidance update triggers a cascade of questions about foundational decisions that were made years earlier and are now difficult to reconstruct.

Watching the Horizon

The timing of any EDDO update remains uncertain. FDA has been clear that its 2026 guidance agenda is a statement of intent, not a commitment, and the combination products regulatory landscape is subject to the same resource pressures and shifting priorities that affect the broader agency. Programs should not plan their regulatory strategy around a specific release date.

What programs should do is use this period purposefully. Revisit how essential drug delivery outputs were identified and whether that process is documented with sufficient rigor. Assess whether the link from EDDOs through development verification and into the production control strategy is complete and auditable. Identify gaps before FDA does.

Suttons Creek works across the full device development lifecycle for combination product programs, and our view across many programs gives us a consistent vantage point on where these gaps tend to form. The teams that navigate regulatory evolution most effectively are not the ones that react fastest, they are the ones that built their programs on a solid foundation in the first place.

AUTHOR

Bryan Bobo, Associate Technical Director, Suttons Creek – With over 9 years of experience in the pharmaceutical industry, Bryan has extensive knowledge of combination product development and what it takes to launch products on the market. He has practical and hands-on experience in various types of drug delivery systems from his years as both a Device Development Engineer as well as project and program management positions. In addition to his direct product development experience, Bryan engages with the global combination product community through his participation on various international standards committees as well as other various industry forums.