Running Global Clinical Trials? PolyPid Shares Operational And Regulatory Insights
By Dalit Hazan, deputy CEO, EVP R&D, clinical, and regulatory affairs, PolyPid
Bringing an investigational therapy from concept to clinic requires more than scientific innovation; it demands operational excellence across borders. Conducting clinical trials is complex by nature, and executing them successfully on a global scale multiplies these complexities significantly. At PolyPid, our global clinical trial journey with our flagship product, D-PLEX100, an investigational prolonged-release antibiotic designed to prevent surgical site infections (SSIs), has taken us across the U.S., Europe, and Israel. Along the way, we have gained invaluable insights into the operational complexities, regulatory navigation, and adaptability required to execute large-scale, multinational studies. From early feasibility studies to pivotal Phase III trials, each stage has offered lessons that continue to shape our approach today.
Regulatory Landscapes Across Global Markets
In recent years, shifts in the European Clinical Trial Regulation clinical trial procedures have introduced new layers of complexity that require increased agility. For smaller biotech companies, this means strategically investing in thorough feasibility assessments and regulatory intelligence to anticipate potential pitfalls. This is essential, particularly in Central and Eastern Europe, where each country presents distinct regulatory characteristics, such as varying timelines for approvals, submission formats, and requirements for local representation.
To address these challenges, we prioritized early, comprehensive regulatory planning, including conducting in-depth feasibility assessments, aligning submission materials with evolving EU Clinical Trial Regulation requirements, and tailoring our strategy to the varying expectations across Central and Eastern Europe. For example, some countries required additional site-specific documentation or had longer approval timelines, which we anticipated and planned for by working closely with seasoned regulatory advisors and maintaining ongoing dialogue with local health authorities. This approach enabled us to navigate the landscape effectively and avoid costly delays.
Operational Lessons Learned
Robust feasibility assessments are essential in determining whether a clinical trial can succeed in a location. Selecting an effective country is foundational, as reversing this decision mid-trial can be logistically and financially prohibitive. This early decision shapes everything that follows, streamlining processes, supporting operational efficiency, and maximizing patient recruitment potential. Through comprehensive pre-selection questionnaires and precise data gathering of patient populations, we assessed factors such as patient population size and availability, investigator experience, prior GCP training, and logistical infrastructure, including the site’s ability to store and administer our investigational product in operational room. Non-negotiables included sufficient staffing and a realistic timeline for activation and recruitment. .
Comprehensive and ongoing hands-on training for clinical sites, coupled with tight sponsor oversight and supervision, is essential to ensure consistent protocol adherence and high-quality data collection. It is unrealistic to assume that site personnel fully grasp complex trial protocols and product applications based solely on written materials. PolyPid implemented proactive measures such as regular on-site visits, maintaining ongoing communication with principal investigators, and providing real-time troubleshooting support. For example, during a site visit in Europe, we discovered a critical staffing shortage that could only have been identified through direct interaction. Promptly addressing this issue by allocating additional personnel and adjusting timelines accordingly, not only preserved site compliance but also reinforced our operational effectiveness and stabilized performance, both affirming our commitment to proactive oversight.
Ensuring data integrity across diverse clinical environments demands rigorous, ongoing collaboration and strong partnerships. At PolyPid, we found that weekly cross-functional meetings between medical, data management, and pharmacovigilance teams, along with frequent interactions with CROs and clinical sites, are essential for identifying and addressing data inconsistencies or logistical challenges in real time, prompt risk identification, and timely issue resolution.
Frequent interactions with CROs have led to significant improvements in several areas. For example, we have been able to better balance site monitoring visits by CRAs, ensuring more frequent reviews of new patient data from high-recruiting sites. These discussions also helped us gain a deeper understanding of clinical sites’ needs and challenges, such as weather conditions that may prevent or delay patients from arriving on time, and to work together to find alternative scheduling options for study visits. Additionally, cross-functional collaboration within the PolyPid team has enabled more effective planning for data review and oversight, including timely evaluation of data deviations, prompt escalation of issues, and implementation of appropriate mitigation and CAPA plans to ensure study continuity and data quality.
Maintaining close partnerships with CROs and clinical sites, combined with clear oversight processes and well-defined reporting protocols, has been key to upholding data quality across all trial locations. Ultimately, strong CRO partnerships, an experienced internal operations team, and clear communication with stakeholders are essential to keeping the trial on track and avoiding delays.
Innovation And Adaptability Shape Success In Clinical Trials
Scaling from regional to global trials demands careful preparation. Companies must focus first on mastering regional regulatory requirements, such as understanding the complexities of FDA submissions in the U.S. versus EMA procedures in Europe. It is also crucial to comprehend variations in standards of care and clinical practices across geographies. For example, treatment protocols and patient expectations can differ markedly between Europe, Israel, and the U.S., necessitating thoughtful adaptation in trial design and implementation.
Clinical trial leaders must also prepare for the unpredictable, recognizing that conducting global trials resembles running a marathon at the pace of a sprint, requiring long-term endurance while simultaneously managing constant pressure, rapid timelines, and fast-moving operational demands. Comprehensive contingency planning, adaptive trial designs, robust communication frameworks, and proactive site engagement form the pillars of successful global clinical trial execution.
To overcome operational, regulatory, and logistical hurdles, companies must demand strategic foresight, clear communication, and continuous learning. By embracing these best practices and innovative strategies, clinical trial leaders can effectively manage the complexities inherent in global clinical research, ultimately driving the development of life-changing medical therapies.
About The Author:
Dalit Hazan, deputy CEO and EVP of R&D, clinical, and regulatory affairs at PolyPid, brings over 25 years of experience in pharmaceutical R&D and regulatory affairs. She has led successful submissions and interactions with global health authorities, including the FDA, EMA, and Health Canada. With a strong background in clinical development and regulatory operations, she has advanced programs from early-stage studies through to approval. Prior to PolyPid, she held senior regulatory roles at Teva Pharmaceuticals. Hazan holds an M.Sc. in Physiology and Pharmacology from Tel Aviv University’s Faculty of Medicine and an Executive MBA from Bar-Ilan University.