Avoiding rework and regulatory headaches through early planning and smarter design alignment

A sponsor approaches Phase 3 with urgency. Their investigational product has been delivered through vials and disposable syringes in earlier studies. Now, they want to switch to a prefilled syringe partway through Phase 3 and eventually commercialize using an autoinjector. The delivery systems have not been standardized, the study syringes vary in configuration, and the needle sizes used at sites are undocumented. Can they bridge to the final presentation? Maybe. But the cost and risk just became very real. 

At Suttons Creek, we have seen this story unfold many times. Compressed development timelines, decentralized sourcing, and incomplete clinical oversight can leave sponsors scrambling to justify bridging between early clinical formats and their commercial-ready delivery systems. 

This challenge is especially acute in combination product programs, where device performance, usability, and patient handling all impact regulatory expectations. Yet with better planning in Phase 1 or 2, much of the downstream burden can be avoided. 

Why Early-Phase Decisions Matter More Than You Think 

During a recent internal discussion, our team reviewed a scenario involving a sponsor planning to accelerate from Phase 2 to Phase 3 in six months using a vial and syringe format. Their intent was to bridge to a prefilled syringe or autoinjector before submission or as a post-approval change. 

This plan is not uncommon, but it is filled with potential pitfalls. Often, early development teams view delivery systems as temporary. As a result, little attention is paid to configuration consistency, human factors risk, or the traceability of components used at clinical sites. 

But from the FDA’s perspective, what you use in the clinic matters. Whether or not your system is technically a combination product, regulators will expect that you understand how your drug is prepared, handled, and administered, and that you can demonstrate safe and effective use across all intended presentations. 

Five Strategic Considerations for Sponsors in Early-Phase Development 

To avoid costly rework, regulatory delays, or the need for full bridging studies later in development, sponsors should consider the following: 

1. Select a Primary Container with Future Material Compatibility in Mind

When starting clinical studies with a vial and disposable syringe, sponsors must consider material compatibility with the intended commercial container closure system. If the vial stopper, plunger, or needle hub materials differ from what will be used in a prefilled syringe or autoinjector, sponsors may face additional extractables and leachables testing and toxicological justification later on. Compatibility assessments should begin early, with the goal of selecting materials that minimize the likelihood of formulation interaction risks across delivery formats. 

Even in early phases, container materials should be evaluated in the context of the long-term commercial strategy. When this alignment is missing, the bridging burden is not just clinical; it can also become deeply technical. 

2. Design for Functional Compatibility Between Presentations

Functional performance or design consideration differences between early-phase and commercial delivery systems can raise significant bridging challenges. These differences might include injection force, delivery speed, dead space volume, and user interface complexity. While these factors may not have a direct influence to the safety or efficacy of your therapy, it’s critical to consider this early on as in many cases they may be scrutinized when the goal is to argue that clinical outcomes remain consistent across formats. 

Needle depth is a common example. A syringe used in early clinical trials might allow for variable needle selection by the site, while the final commercial system (such as a prefilled syringe or autoinjector) will have a fixed needle length. Differences in injection depth can influence absorption and pharmacokinetics, particularly for subcutaneous products. Similarly, injection force profiles and user-applied pressure can affect consistency and user experience. 

To reduce variability and support future bridging arguments, sponsors should aim to control or standardize device parameters early, including providing consistent components to clinical sites whenever possible.  

3. Establish a Baseline IFU and Device Description — Even in Early Trials

If your clinical kit requires assembly, reconstitution, or multi-step preparation, regulators expect that patients or providers will be able to do it safely. While some early-phase teams rely on site training alone, the lack of a clearly documented instructions-for-use (IFU) can become a risk and lead to unexpected use errors or be a missed opportunity to evaluate earlier iterations of patient instructions to inform future commercial needs.  

Sponsors should consider conducting a formative human factors study during early development. The goal is not to finalize labeling at this stage, but to reduce risk and inform a use model that can be consistently applied and improved throughout the program. 

4. Design a Development Plan That Anticipates Future Bridging

Whether the plan is to switch delivery systems during Phase 3 or after approval, define the target presentation early and ensure that all stakeholders, including clinical operations and regulatory affairs, are aligned. This alignment enables strategic decisions about data collection, study design, and human factors activities that support future transitions. 

Consider whether a bridging justification will be possible based on delivery performance, component similarity, and user handling characteristics. If not, be prepared for additional clinical or usability studies and include these in your timelines and budget. 

5. Treat Co-Packaged Kits as Combination Products

Even if a product uses simple delivery components, such as a vial co-packaged with a commercially available syringe and needle, FDA considers co-packaged products to be combination products. As such, sponsors are expected to apply Design Controls to the full user system, including the interactions between drug and device components. 

While the development path and overall technical risk for these configurations may be more streamlined compared to integrated or novel delivery systems, there is still an expectation that sponsors apply appropriate Design Control principles and risk management activities. This includes: 

• Defining user needs and intended use for the system 

• Developing a Design History File (DHF), at minimum at the system level 

• Conducting risk assessments, including use-related risk analysis 

• Evaluating human factors considerations 

• Generating in-use compatibility data to support stability and handling 

Neglecting these requirements early can result in gaps at the time of NDA or BLA submission, especially if the product is intended for self-administration or used in settings where site training is limited. 

There Is Flexibility, but Know the Risks 

It is possible to switch delivery systems mid-study or even post-approval. We have seen sponsors pursue this approach successfully, moving from vial and syringe to prefilled syringe or even to autoinjector within a single clinical program. But each change introduces new considerations that must be justified scientifically and operationally. 

From a regulatory standpoint, sponsors must be prepared to explain how clinical outcomes remain consistent, how use-related risks are mitigated, and how manufacturing controls ensure product quality across formats. The technical file must tell a coherent story from early development to final presentation. 

Additionally, these delivery changes often introduce ripple effects across supply chain, packaging, and manufacturing operations. A change from a vial to a prefilled syringe may require new fill-finish capabilities, revised shipping validations, and updated inspection processes. These are not trivial operational shifts, and sponsors must weigh the total impact of delivery system changes across quality, cost, and timeline. 

Final Thoughts: Build With the End in Mind 

In today’s environment, speed is important, but so is durability. The most efficient development programs are not those that cut corners. They are the ones that make thoughtful decisions early to reduce surprises later. 

If your program will transition from a simple vial-syringe configuration to a more advanced prefilled or automated delivery system, take the time to plan for that evolution now. Align your device configurations early. Evaluate materials for compatibility. Control site variability. Coordinate across teams. And most of all, avoid the false economy of deferring delivery considerations to a future phase. 

At Suttons Creek, we have helped clients navigate these transitions with minimal rework by identifying comparability gaps early and developing strategies that are tailored to real-world regulatory expectations. 

For expert support in early-phase delivery system strategy, combination product development, or regulatory planning, contact us.