Combination Product Industry News & Guidance

Launch is just the beginning…

For combination products, launch isn’t the finish line—it’s the point where the lifecycle becomes commercially real and operationally exposed. Post-market change is inevitable, driven by forces that rarely align to commercial timelines: 

• Component or material obsolescence 

• Quality signals and corrective actions 

• Scale-up, automation changes, and site transfers 

• Supply chain resilience initiatives 

• New indications or expanded patient populations 

• New features and product improvements 

The risk isn’t change itself—it’s uncontrolled change. If decisions are made reactively or in silos, the outcome can be avoidable safety risk, regulatory friction, supply disruption, and in the worst cases, recalls or market withdrawal. This is not a “manufacturing problem” or a “quality issue.” It’s a strategic exposure that requires early visibility, clear decision rights, and disciplined governance. 

Combination products are not simply devices paired with a drug.

They are complex systems that depend on consistent performance across three domains: the formulation, the delivery mechanism, and user interaction. 

Because of this, small changes often have non-obvious second- and third-order effects. A material substitution may satisfy component requirements but alter friction, force profiles, or inspection sensitivity. A labeling update may appear administrative but change how users interpret feedback or error states. A manufacturing tweak may interact with automation in ways that were not relevant at development scale. 

The challenge is not that these effects exist—it’s that they are often recognized too late to manage deliberately. When that happens, decisions shift from being proactive and strategic to being reactive and time-bound, increasing the likelihood of delays, cost escalation, and reputational impact. 

These dynamics become clearer in a post-launch change scenario involving a marketed pre-filled syringe (PFS), where a “small” material change quickly becomes a multi-stakeholder decision across performance, compliance, and supply continuity. 

Example: 

Following the addition of Octylphenol Ethoxylate (OPE) to the REACH Authorization List in 2017, Dupont’s Liveo™ 365 began to be phased out in many pharmaceutical applications, including lubrication of glass barrels for pre-filled syringes (PFSs). The lubricant is a critical component of the PFS, affecting both essential functions (break loose glide force, dose accuracy) and patient safety (impurities). Although Dupont had a replacement material available, changes were required across the supply chain (MAHs, CMOs, marketing companies) including design documentation, manufacturing processes, product labeling, and regulatory filings. 

This type of change forces a broader question than “can we substitute the material?” It requires deliberate alignment on what is being protected—performance, safety, submission integrity, and continuity of supply—while coordinating execution across multiple organizations with different responsibilities and incentives. Without that alignment, change becomes vulnerable to fragmented assessments, inconsistent testing logic, and late-stage surprises. 

Many organizations rely on formal change control to manage post-launch evolution.

While necessary, change control alone does not guarantee strong outcomes. The differentiator is strategic change assessment: the ability to evaluate impact early, assign accountability clearly, and make decisions that remain defensible under regulatory and commercial pressure. 

Effective post-launch performance depends on the ability to: 

• Understand how a proposed change interacts with regulatory commitments and affects key partners 

• Anticipate whether design control assumptions are being challenged 

• Recognize when human factors or user behavior could be indirectly affected 

• Evaluate manufacturing robustness rather than minimum compliance 

• Decide where testing adds clarity versus where it adds delay 

• Execute and effective global regulatory strategy particularly in cases of mutual dependencies 

This assessment is most effective when it is structured, but not mechanistic. Frameworks and checklists create consistency, but outcomes still depend on judgment informed by experience with similar products and markets. Just as importantly, decision ownership must be clear. Over-involvement slows execution, under-involvement increases the likelihood of missed impacts. Defined roles help balance speed with risk awareness. 

The value of this approach is visible in what it prevents and what it enables: 

• No supply disruptions or field actions 

• Regulatory acceptance through clear, defensible rationale and evidence 

• Timely and efficient global deployment with a well-managed logistical rollout 

• Post-launch change management treated as a repeatable capability within the QMS 

Post-launch change is not a sign that development fell short.

It reflects the reality that combination products operate in dynamic technical and commercial environments, needing to consider the requirements and nuances of both drug and device constituents. The differentiator is not whether change occurs, but whether it is handled intentionally rather than reactively, and collaboratively rather than in isolation. That difference is rarely visible at launch—but it becomes decisive over time.  

Change is inevitable. Late recognition is optional. The advantage comes from making deliberate decisions early—before urgency drives them, and utilizing experienced resources that can assist before, during, and after those changes.. 

Take the next step toward understanding the impact of your proposed post-launch change…

Our combination product lifecycle management experts have crafted a proprietary online tool that supports the evaluation of impact and requirements of post-market product changes. To add this tool to your own toolbox, simply fill out the below form.

CO-AUTHORS

Parth Kothari, Senior Principal Consultant, Suttons Creek –Parth is a results-driven leader with over 13 years of experience in the regulated healthcare industry, specializing in the development and commercialization of complex medical devices and combination products. He has successfully led programs from concept through launch at global pharmaceutical and medical device organizations. Link to bio.

Michael Koucky, Principal Consultant, Suttons Creek – Michael is an engineer with more than 10 years of experience providing technical and design control expertise to the drug-device/biologic-device combination product and medical device industries. He has provided successful support to clients through all phases of the product life-cycle, from new product development through design transfer, life-cycle management, and end-of-life. Link to bio.