Combination Product Industry News & Guidance

Rescuing a Time-Critical IND Amendment for a Clinical-Stage Injectable Program

The Challenge

A clinical-stage biopharma company developing an injectable therapy in a standard prefilled syringe engaged Suttons Creek for support with two priorities:

1. Developing a bridging strategy to an eventual auto-injector configuration
2. Light review support for an upcoming IND amendment

However, at project kickoff the sponsor revealed that the IND amendment was only two weeks away from submission, and they required full review of all combination-product–related content.

Once the draft documents were received, it became clear the company faced a deeper issue:
They had no device design control documentation, no combination-product QMS structure, and no design history file (DHF).

The sponsor’s team believed their CMO maintained the necessary documentation—a common misconception for first-time combination-product developers.

Initial feedback about these gaps was met with an understandable concern about whether the submission could proceed at all.

Our Approach

Suttons Creek moved quickly to stabilize the submission and create a realistic regulatory pathway forward.

1. Rapid triage of submission-critical gaps

We immediately evaluated:

1. What documentation actually existed
2. What functional and stability data the CMO could provide
3. Whether the absence of design controls created a safety or performance risk
4. Which elements FDA would expect in a Phase 2 IND amendment for a standard prefilled syringe

Our review determined that:

• The components were sourced from well-established platform suppliers
• The CMO had valid performance and container-closure integrity data
• No underlying patient-safety risks were present
• The missing design controls represented a documentation deficiency, not a product-risk deficiency

This allowed the submission to move forward with caveats and clear regulatory risk communication.

2. Building trust through transparent, risk-based guidance

We held a structured session explaining:

1. Combination-product GMP requirements under 21 CFR Part 4
2. FDA’s explicit expectation that design controls apply even during investigational stages
3. The long-term risks of proceeding without a device DHF
4. Options to remediate the compliance gap without delaying essential clinical progress

Once the sponsor understood why the documentation was required, alignment and collaboration improved.

3. Salvaging the IND amendment

Suttons Creek:

1. Revised all PFS-related Module 3 content
2. Inserted defensible descriptions of testing performed by the CMO
3. Integrated supplier data (e.g., extractable volume, injection performance, breakloose/glide force)
4. Right-sized the depth of information to typical expectations for Phase 2 PFS submissions
5. Built a clear narrative reflecting existing controls and planned future work

With careful messaging, the submission became acceptable for a Phase 2 filing.

4. Establishing a compliant combination-product program

After stabilizing the immediate submission, the sponsor engaged Suttons Creek to:

1. Build foundational combination-product QMS elements
2. Create a complete DHF for the prefilled syringe
3. Develop the bridging and development plan for the future auto-injector
4. Support vendor selection and regulatory strategy for the device evolution

This work transformed a high-risk situation into a structured, regulator-ready development pathway.

The Result

The sponsor successfully submitted the IND amendment on schedule with a regulatory-sound package.

With Suttons Creek’s support, they were able to:

• Avoid submission delays despite lacking critical device documentation
• Understand and implement Part 4 design control expectations
• Establish a full combination-product QMS and DHF
• Advance the program toward auto-injector development with a clear, compliant roadmap
• Build a durable partnership with their device suppliers and CMO

What began as a two-week emergency became a long-term strategic relationship that set the foundation for multiple successful development programs.

AUTHOR

Jonathan Amaya-Hodges, Director of Consulting, Suttons Creek – Jonathan has over 16 years of multidisciplinary experience in regulated medical products (drugs, biologics, medical devices, and combination products) at multiple global companies. He has practical experience in Development/Engineering, Quality Assurance, and Regulatory Affairs for various types of combination products with a focus on drug delivery. Additional background includes digital health (including smart packaging/connected devices and software as a medical device, or SaMD) and in vitro diagnostics, along with clinical development (bridging) and lifecycle management for combination products. Jonathan engages with the global combination product community by speaking at conferences, lecturing in courses, serving key roles within prominent industry organizations, and interfacing with regulators on a variety of topics.