Full SPaeDD Ahead

It’s true what they say about strength in numbers; pooling both resources and expertise allows those collaborating to better tackle the challenges associated with complex research and development. The result is an approach greater than the sum of its parts.

In my view, collaboration is particularly crucial in areas of drug development with great unmet medical needs, such as the pediatric field. Over the past few decades, pediatric drug development has not kept up with the progress made by medicines tailored to adults, and there are many limitations that disincentivize companies from formulating medicines specifically for children. Children’s physiological make-up will alter as they age, with factors such as the composition of intestinal fluids, gut permeability and metabolism all changing over time. In addition, there is a distinct lack of methodologies and clear guidelines available to support pediatric medicine development.

Collaboration can help solve some of these problems. I’d like to draw attention to the SPaeDD (Smart Paediatric Drug Development) project in the UK, which has brought together academic research institutions and pharmaceutical companies and contractors, including Catalent Nottingham (formally Juniper Pharma Services), Pfizer, AstraZeneca and Aston University. Co-funded by Innovate UK, this project ran from 2014 to 2018 to refine and clarify best practices for pediatric drug development. The project focused on research areas considered critical for pediatric drug development, including drug exposure, taste, and medicine acceptability.

It is crucial that drug developers can accurately predict exposure of drugs for children. Children are not just small adults – they have a very different physiology that can affect absorption, distribution, metabolism, and excretion profiles for drugs. Accurately predicting and understanding this exposure can greatly accelerate the drug development process. Unfortunately, this is something that the industry doesn’t have a great hand on with respect to a harmonized approach and methods. The SPaeDD project tackled this by creating a predictive mathematical model for age-related biorelevant dissolution testing for pediatric formulations. The successful outcome highlighted how predictive models can inform our understanding of exposure, due to the clear effect of age-related physiological parameters on oral dosage dissolution.

SPaeDD also considered taste assessment and taste masking. This is important when developing medicines for children because children are notorious for their aversion to unpalatable foodstuffs and medicines, which makes the administration process for parents and adults very difficult and stressful! The pediatric drug development process is, unfortunately, no easier, with a distinct lack of in vitro and in vivo taste assessment tools hindering progression along the pipeline. The SPaeDD project comprehensively reviewed the available tools used to evaluate bitter tasting medicines. This aided the consortium in fully understanding the gaps in the toolkit currently available to help direct research. A technical review also helped create an open access quality target product profile (QTPP) for taste masking – supporting future pediatric drug development projects. By reviewing and analyzing all past literature in this critical area of work, the SPaeDD project created an excellent springboard for future research projects to hit the ground running.  

The final output of the SPaeDD project was to improve understanding of pediatric “medicine acceptability”. This is the overall ability of an individual to use a medicinal product as intended. Factors like appearance, volume, smell complexity of modification before administration, and the required dosing regime all fall under the acceptability umbrella. Prior to the SPaeDD project, there was no guidance on how to conduct or report on acceptability testing. To address this, the consortium used a systematic literature review to create an algorithm that generated data concerning the acceptability of a range of formulations across the pediatric age range. By providing a systematic approach for dosage form selection, this tool will help guide size and volume selection for particular dosages.

Consolidating knowledge relating to drug exposure, taste assessment, and acceptability is critical for addressing the unmet medical needs of children. The SPaeDD project has resulted in the development of a number of novel and refined toolkits, which should facilitate the development of pediatric medicines. I have no doubt this would have been impossible to achieve in the same timeframe by one company alone! From computer algorithms to in vitro modeling, the SPaeDD project required a diverse skillset that could only be found through a multi-partner consortium. And it has reaped great rewards, with the publication of a wealth of literature already receiving regular citations (1). Moreover, the tools created have received great interest from industry – it has certainly been beneficial for pediatric medicine research efforts at our company.

Collaborative approaches are continuing to transform the field of pediatric medicine. For instance, programs such as the European Paediatric Formulation Initiative bring together pharmaceutical organizations, hospitals, and academic institutions to resolve issues associated with pediatric formulations. Another example is the Catalent Applied Drug Delivery Institute partnership with the Department of Pharmacy Practice at Rutgers University. This collaboration aims to identify diseases that require pediatric-friendly formulations, and to build awareness and advocate for targeted translational research. For each of these programs, there is one crucial common feature: the ability for all organizations involved to draw on unique strengths and resources to achieve an overall aim. We can make huge strides forward if we collaborate.