Certara, the global biosimulation technology-enabled drug development company, and Paidion Research, Inc., a paediatric clinical research organization (CRO), announced a new partnership dedicated to promoting more efficient and reliable drug development for paediatric patients.

The partnership harnesses Certara’s unmatched biosimulation (modeling and simulation) and regulatory writing capabilities, with Paidion’s regulatory strategy and paediatric clinical trial management expertise to address the critical challenges of bringing new therapies to children.

“The US Food and Drug Administration (FDA) reports that paediatric product development initiatives have resulted in improved product labelling, increased identification of adverse events, and the development of new paediatric formulations. However, 42 percent of recent paediatric trials have failed to establish either safety or efficacy,” said Certara chief executive officer (CEO) Edmundo Muniz, MD, PhD. “Both Certara and Paidion are passionate in their scientific commitment to developing safer medicines for children, as they are our most precious resource.”

Paidion CEO Barry Mangum, PharmD, FCP, added, “Sick children represent the most vulnerable population in the world. As our understanding of paediatric patients has grown, we recognize that they manifest many diseases and side effects of the related medical treatments differently than adults. Combining Certara’s expertise in both pharmacokinetic/pharmacodynamic (PK/PD) and physiologically-based PK (PBPK) modelling with Paidion’s success rate in conducting paediatric clinical trials will be transformative.”

Both FDA and the European Medicines Agency (EMA) have legislated that pharmaceutical companies must develop label guidelines for paediatric drug development. This requirement has resulted in an increased need for new scientific approaches, a clear aim of the Certara/Paidion partnership.

One of the greatest challenges in paediatric clinical research is defining a safe and effective dose or dose range for this patient population that can span premature neonates to adolescents. There are significant physiological differences between children and adults that can affect the absorption, distribution, metabolism, and elimination (ADME) of medications. Certara has developed specific technologies and strategies to inform proper dose selection, including PK/PD simulations using sparse data analysis and its Simcyp Pediatric PBPK simulator. The simulator captures changes in physiology and enzyme/transporter development that are particularly prominent in children from birth to two years of age. The Simcyp Simulator is used by most leading pharmaceutical companies and international regulatory agencies. In 2012, FDA voted unanimously in support of extending the use of PBPK modelling for paediatric drug development.

In addition to physiological differences between paediatric populations, there are sizeable challenges in conducting paediatric clinical trials, which include study design, patient identification, recruitment and retention, and determining clinical benchmarks. The available pool of paediatric populations for many target indications is much smaller than adults, and ethical constraints signi?cantly limit the number of participants. Paidion’s paediatric focus, as well as its formation of sustainable neonatal and paediatric intensive care unit and paediatric clinical site networks will help resolve those challenges.

Current FDA and EMA guidelines recommend that dose selection for paediatric studies be based on all available prior information, starting with what has been learned in adult populations. This guidance translates into an ethical imperative to use biosimulation to inform paediatric drug development whenever possible, minimizing the impact on children that must enroll in clinical trials. At the same time, clinical trials are still a necessary part of drug development and they must be organized with a paediatric patient-centric focus. By combining expertise in biosimulation, paediatric clinical trial management, and regulatory strategy and writing, the Certara/Paidion partnership intends to greatly expand the number of new medications available to children.