During the 2025 Combination Products Summit in Providence, RI, leadership from the FDA’s Office of Combination Products (OCP) addressed growing industry concerns surrounding the agency’s draft guidance on essential drug delivery outputs (EDDOs). While the guidance remains under revision, FDA officials emphasized that stakeholder feedback is actively shaping the final version.
Clarifying the Status of the Draft Guidance
The draft EDDO guidance has raised questions across the combination product sector, particularly regarding when and how its recommendations should be applied. Although some review teams reference portions of the document during investigational new drug (IND) reviews, OCP leaders stressed that it is still a draft—and not uniformly applicable.
OCP Deputy Director Patricia Love explained that certain concepts may still be relevant during specific reviews, but manufacturers should consult their IND review division when uncertain. Product-specific clarification, she emphasized, remains the most reliable approach.
OCP Director James Bertram reassured attendees that the agency is taking industry feedback seriously and is making deliberate revisions. He noted that the FDA is not working toward a fixed deadline. The priority, he said, is “a thorough job” and a guidance document that reflects real-world challenges in combination product development.
Key Topics: Sample Sizes, Control Strategies, and Submission Expectations
Panelists also addressed several practical questions that manufacturers frequently encounter:
Sample Size Expectations
Ashley Boam of CDER explained that the agency expects statistically justified sample sizes based on device risk level. Requirements may vary depending on the complexity and intended use of the drug–device combination.
Choosing Qualitative vs. Quantitative Specifications
Boam noted that the appropriate test method depends on the specific EDDO and how performance is defined for the product.
Control Strategy Placement in Applications
Love advised placing device control strategy information in parallel sections of the eCTD where drug controls appear, unless otherwise directed.
Pre-IND Questions and Level of Detail
FDA representatives encouraged sponsors to match the detail in their questions to the level of feedback desired. Early conceptual questions require less documentation, while requests for detailed commitments require more complete data.
Device Component Listings on Form 356H
Sponsors are not required to list device components, but they must identify the product as a combination product and include all relevant establishment information.
Addressing Practical Challenges
Industry representatives raised concerns about logistical hurdles—such as providing multiple human-factor samples for certain devices or responding to FDA requests for information (RFIs) under tight timelines.
FDA officials acknowledged these challenges but noted that many review deadlines and internal timelines necessitate prompt responses. In cases where full sample submissions are infeasible, alternatives may be acceptable, but should be discussed with regulators early.
A Collaborative Path Forward
Overall, FDA leaders reinforced that the agency is listening closely as it refines the EDDO guidance. The goal, they said, is a practical, science-driven framework that supports innovation without compromising safety.
At EMMA International
EMMA International helps combination product developers navigate evolving FDA expectations, including control strategy development, documentation readiness, and pre-IND engagement. Our experts provide end-to-end support to ensure your programs remain compliant, risk-based, and aligned with the latest regulatory thinking.
For more information on how EMMA International can assist, visit www.emmainternational.com or contact us at (248) 987-4497 or info@emmainternational.com.
References:
Al-Faruque, F. (2025, November 20). OCP chief reassures stakeholders on EDDO guidance. Regulatory Focus. Regulatory Affairs Professionals Society.
U.S. Food and Drug Administration. (2024). Draft guidance for industry and FDA staff: Essential Drug Delivery Outputs (EDDOs). U.S. Department of Health and Human Services.
AFDO/RAPS Healthcare Products Collaborative. (2025). 2025 Combination Products Summit Proceedings. Regulatory Affairs Professionals Society.
