The rise of biosimilar insulins has opened new opportunities for improving access to affordable diabetes care. Unlike small-molecule generics, biosimilars must prove their similarity through a rigorous set of requirements, particularly phase I pharmacokinetic and pharmacodynamic trials. At the heart of this process lies the euglycemic glucose clamp, the recognized gold standard for measuring insulin action.
A review published in March 2025 by Profil’s lead scientists Tim Heise and Hans de Vries in Diabetes, Obesity and Metabolism summarized all clamp-based studies that supported FDA and EMA approvals of biosimilar insulins. The review offers an excellent overview of study designs and regulatory outcomes, and it provides an opportunity to highlight another important point that complements its findings. Profil is the only contract research organization worldwide capable of performing fully automated clamp studies. Because of this unique position, Profil has been involved in all clinical trials that led to the approval of biosimilar insulins by both the FDA and the EMA1.
The Role of Glucose Clamp Studies
For biosimilar insulins, clamp studies are indispensable. Regulators rely on clamp-derived pharmacokinetic and pharmacodynamic endpoints to confirm that the biosimilar behaves identically to the reference insulin. These studies are often more sensitive than large-scale clinical efficacy trials when it comes to detecting small differences in absorption profiles or metabolic action. Without the automated clamp method, the approval of biosimilars would not be possible at the level of confidence required by the FDA and EMA.
Manual and Automated Approaches
Traditional clamp studies were conducted manually. Trained personnel measured glucose levels at fixed intervals and adjusted infusion rates accordingly. While this approach was innovative at the time, it introduced significant limitations. Operator variability was a constant challenge, and the risk of drifting away from the glucose target increased during longer clamps. The manual process was labor intensive, particularly for ultra-long clamps that extended across one or more days, and reproducibility across sites was limited.
The automated clamp system was developed by Profil to address these issues. By combining continuous glucose monitoring with algorithm-driven infusion control, automation provides a level of precision and reproducibility that manual methods cannot achieve. Blood glucose can be held within a very narrow range. Human bias is eliminated, and data quality is significantly enhanced. Automated systems also make it feasible to conduct multiple clamps simultaneously and to extend the duration of studies, which is necessary for evaluating ultra-long acting insulins. For regulators who demand consistency and precision, the automated clamp system is the gold standard.
Profil’s Technological Edge
Profil has been at the forefront of clamp methodology for decades. Its CE-certified ClampArt system represents the most advanced automated glucose clamp available today. The system integrates real-time glucose measurement with precision infusion pumps and advanced algorithms. It can run ultra-long clamps with stable performance and is capable of operating continuously without failure.
At its clinical site, Profil maintains the capacity to conduct up to twenty-eight clamps in parallel, operating around the clock. This infrastructure enables thousands of clamp hours per year, ensuring both scalability and reliability. Each system is built for ultra-low infusion rates that must remain stable for extended periods of time, and Profil’s record of reliability demonstrates the robustness of its technology.
Crucially, Profil is the only contract research organization worldwide that offers fully automated clamp studies. This exclusivity has made it the preferred partner for biosimilar insulin developers across the globe.
Profil’s Role in Biosimilar Insulin Trials
The March 2025 review article documented the clamp trials that formed the foundation for FDA and EMA approval of biosimilar insulins. Each of these trials depended on precise pharmacodynamic data to establish equivalence with the reference products through fully-automated clamps.
Every biosimilar insulin currently approved by the FDA and EMA required Profil’s expertise. The company did not only provide the clamp data itself but also contributed to study design, subject recruitment, regulatory consultation, and statistical analysis. This comprehensive involvement ensured that sponsors could present robust packages to regulators, accelerating approval timelines and reducing risk.
Overview of biosimilar insulins approved by FDA and EMA. HV: healthy volunteers; T1DM: type 1 diabetes mellitus
1: Only EU approved; others are US and EU approved.1
The Importance of Automation and Exclusivity
The importance of Profil’s exclusivity extends beyond technical capability. For sponsors, working with Profil means minimizing regulatory risk. Automated clamps provide data that is consistent, reproducible, and trusted by regulators. For regulators, the use of automated clamps ensures that evaluations are based on the highest possible standard of precision. For patients and healthcare systems, the outcome is faster approval of biosimilars, leading to broader access to affordable therapies.
Profil’s role in every currently approved biosimilar insulin trial demonstrates that automation is not merely an incremental improvement over manual methods but rather a prerequisite for regulatory acceptance. It also underscores that Profil has become indispensable in the global biosimilar insulin landscape.
Beyond Biosimilars
While biosimilars represent a highly visible area of impact, Profil’s clamp expertise extends further. The company plays a central role in first-in-human insulin studies, in trials of novel ultra-long acting insulin analogues, and in broader metabolic disease research including diabetes, obesity, and fatty liver disease. Its commitment to methodological innovation ensures that clamp studies remain not only precise but also efficient and adaptable to emerging therapies.
Conclusion
The development and approval of biosimilar insulins represent one of the most significant advances in diabetes care in recent decades. Their success depends on the precision of euglycemic clamp studies, and in this field Profil stands alone. With its proprietary ClampArt system, unparalleled throughput, and regulatory expertise, Profil is the only contract research organization worldwide capable of delivering fully automated clamps at scale.
This unique position explains why Profil has been involved in the clinical trials supporting every biosimilar insulin currently approved by the FDA and EMA. It also highlights the company’s broader role in advancing metabolic research and setting global standards for methodological excellence. Profil is not simply a service provider. It is a scientific partner at the center of biosimilar insulin development and an essential contributor to the future of diabetes care.
You would like to take advantages of Profil's expertise for biosimilar insulins? Contact us today and we can schedule a call to discuss how we can support your biosimilar insulin journey.
Source:
1Heise