For small and emerging biopharmas, expanding a clinical trial beyond the United States can be an important step toward reaching more patients and supporting future regulatory submissions. But it can also introduce a level of operational complexity that may be unfamiliar to a sponsor who’s only managed sites stateside.

A trial that worked well in America may need significant adjustments once sites in other countries get involved. For instance, data may cross borders under different privacy requirements, and safety information may need to move through additional reporting systems. Even the way a sponsor communicates with investigators and manages sites can require a different approach.

These obstacles can present challenges, but they aren’t insurmountable. The key is to understand the differences before the first international site goes live. Establishing strong processes up front is the first step. Here’s a closer look at four essential areas to focus on. 

Step 1. Start with a global approach to data privacy

Data privacy is one of the first areas where U.S. trial models often encounter new requirements.

Clinical trial sponsors already have obligations to protect participant information in U.S. studies, but expanding internationally can introduce additional rules governing how personal data is collected, processed, and transferred. 

In Europe, for example, the General Data Protection Regulation (GDPR) places specific requirements on international transfers of personal data outside the European Economic Area. The European Data Protection Board notes that these transfers must meet the conditions established under Chapter V of the GDPR. 

This guidance means a sponsor preparing for a global trial should consider data privacy during study planning instead of treating it as a documentation issue to address down the road. Sponsors need to understand where clinical data will be processed and whether their existing vendors and technology platforms are appropriate for the countries involved.

The regulatory landscape is also evolving. Case in point: The European Health Data Space (EHDS) Regulation. EHDS entered into force in March 2025 and established a framework for the use and exchange of electronic health data in the European Union. Most of its provisions will take effect gradually, beginning in 2029. However, it’s important to prepare. 

For sponsors currently planning global studies, privacy requirements should be a main focus. If you’re unsure where to begin, connect with local experts to identify parameters you may not already be aware of. This step alone can alert you to potential issues you might miss coming from the U.S. market. 

Step 2. Build safety case processing for a global study

Safety reporting becomes significantly more complicated when trials extend beyond U.S. borders.  There’s a good chance you’re familiar with the IND safety reporting framework, but once international sites are added, you’ll need to account for additional reporting obligations and systems in the countries where your study is conducted.

The European Union is a good example. Sponsors conducting clinical trials in Europe use EudraVigilance to report suspected unexpected serious adverse reactions (SUSARs). In fact, the system includes a clinical trial module specifically for these reports. 

Your team needs to be able to report safety information from trial sites, regardless of where they’re located. Sponsors, in particular, need a defined process for receiving cases from investigators, evaluating the information, and determining what needs to be reported. It’s crucial everyone on the ground understands their responsibilities before a trial begins.

Recent changes in the United States also make this an especially important time for sponsors to review their safety reporting infrastructure. The FDA now requires commercial IND sponsors to use the ICH E2B(R3) data standard when submitting premarketing safety reports electronically. 

The broader move toward standardized electronic safety reporting doesn’t eliminate regional differences. However, it does make it even more important for emerging sponsors to understand how their safety processes will work across jurisdictions.

If you’re preparing to expand into global trials, evaluate case intake and reporting processes before the study starts. That includes who’s responsible for each step and making sure the safety systems you use align with regulations in the countries involved. 

Step 3. Rethink how you manage international sites

One of the most common mistakes U.S.-based sponsors make is assuming their domestic management approach will apply everywhere else. 

In reality, clinical research sites operate within their own healthcare systems and professional cultures. Expectations around communication, decision-making, and sponsor relationships often vary considerably between countries. A site may have extensive clinical research experience but operate differently from a U.S. site, while another may need more hands-on support during study start-up.

The goal should be consistency without assuming that every site needs to be managed exactly the same way. For that to happen, you need to closely coordinate with local teams. Professionals on the ground can provide guidance on how investigators typically work with sponsors and CROs, and where communication problems tend to arise. They can also help you understand where a seemingly minor difference in local practice could affect the study overall.

Another thing to remember is that sites in less mature clinical research markets often require closer management, with monitoring and training adapted to the site’s specific capabilities. Building relationships with local investigators and site personnel can help streamline this process. 

This approach aligns with  ICH E6(R3), as the revised Good Clinical Practice guideline places greater emphasis on quality by design, risk-based approaches, and effective sponsor oversight. 

Step 4. Don’t be afraid to ask for outside support

Moving from U.S.-only trials to global research often exposes gaps that were easy to overlook when every site operated within the same familiar framework. But it’s important to identify those gaps before any international sites are activated.

If you’ve made it this far, then you know you must:

• Review safety workflows, safety teams, and regulatory systems
• Develop site management strategies that align with local differences
• Tailor communication to each country’s culture and standards

However, for many small and emerging biopharmas, building these capabilities internally isn’t always practical. The good news is that experienced global partners can provide local knowledge and help you maintain oversight of any study.

At Harbor Clinical, we regularly work with organizations to expand from U.S.-based research into global clinical trials. We have team members all over the world who help sponsors manage international studies while providing the local expertise needed to navigate different markets.

To learn more about how we can support you and your team as you expand into international trials, get in touch and click here and fill out the digital contact form. We look forward to supporting your development strategy.