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Introduction: Regulatory decisions on paediatric investigation plans (PIPs) aim at making effective and safe medicines timely available for children with high unmet medical need. At the same time, scientific knowledge progresses continuously leading frequently to the identification of new molecular targets in the therapeutic area of oncology. This, together with further efforts to optimise next generation medicines, results in novel innovative products in development pipelines. In the context of global regulatory development requirements for these growing pipelines of innovative products (e.g. US RACE for children Act), it is an increasing challenge to complete development efforts in paediatric oncology, a therapeutic area of rare and life-threatening diseases with high unmet needs.Objective: Regulators recognise feasibility challenges of the regulatory obligations in this context. Here, we explain the EU regulatory decision making strategy applied to paediatric oncology, which aims fostering evidence generation to support developments based on needs and robust science. Because there is a plethora of products under development within given classes of or within cancer types, priorities need to be identified and updated as evidence evolves. This also includes identifying the need for third or fourth generation products to secure focused and accelerated drug development.Conclusion: An agreed PIP, as a plan, is a living document which can be modified in light of new evidence. For this to be successful, input from the various relevant stakeholders, i.e. pa-tients/parents, clinicians and investigators is required. To efficiently obtain this input, the EMA is co-organising with ACCELERATE oncology stakeholder engagement platform meet-ings.(c) 2022 Elsevier Ltd. All rights reserved.

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population.

Child trafficking is a form of modern slavery, a rapidly growing, mutating and multifaceted system of severe human exploitation, violence against children, child abuse and child rights violations. Modern slavery and human trafficking (MSHT) represents a major global public health concern with victims exposed to profound short-term and long-term physical, mental, psychological, developmental and even generational risks to health. Children with increased vulnerability to MSHT, victims (in active exploitation) and survivors (post-MSHT exploitation) are attending healthcare settings, presenting critical windows of opportunity for safeguarding and health intervention.Recognition of child modern slavery victims can be very challenging. Healthcare providers benefit from understanding the diversity of potential physical, mental, behavioural and developmental health presentations, and the complexity of children’s responses to threat, fear, manipulation, deception and abuse.Healthcare professionals are also encouraged to have influence, where possible, beyond the care of individual patients. Research, health insights, advocacy and promotion of MSHT survivor input enhances the collaborative development of evidence-based approaches to prevention, intervention and aftercare of affected children and families.

Accepted manuscript version, licensed CC BY-NC-ND 4.0. Published version available at https://doi.org/10.1136/ejhpharm-2018-001562. Objectives: The main objective was to investigate Y-site compatibility of intravenous drugs with one standard total parenteral nutrition (TPN) admixture for preterm infants. Since micro-precipitation was observed in the water phase after addition of trace elements, the concentration effect on micro-precipitation formation developed as a sub-goal. Methods: Seven drugs (ampicillin, ceftazidime, fluconazole, fosphenytoin, furosemide, metronidazole and paracetamol) were mixed in three mixing ratios with one preterm TPN admixture. Samples were investigated within 1 hour and again after 4 hours. Precipitation was studied in a lipid-free version called TPNaq by light obscuration, turbidimetry and visual examination. Emulsion stability data were assessed by light obscuration and laser diffraction. pH was measured to assess the theoretical risk of precipitation and emulsion destabilisation. The influence of different concentrations of trace elements on precipitation was investigated by visual examination, turbidimetry and light obscuration. Results: Ampicillin, ceftazidime, fosphenytoin and furosemide led to precipitation after mixing with TPNaq. In some samples of TPN and fluconazole, metronidazole and paracetamol, the emulsion droplet size was above the acceptance limit, although this might also be inherent to the TPN admixture. An unexpected formation of micro-precipitate correlating with increasing amounts of added trace elements might be caused by an interaction of cysteine and copper, and complicated the compatibility assessment with drugs. Conclusions: The micro-precipitate resulting from the addition of trace elements should be investigated further. This study did not provide sufficient evidence to recommend Y-site infusion of the tested drugs and the preterm admixture; however, it might offer some additional support to other compatibility data.

The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI). A session at the workshop was dedicated to acceptability assessments and focused on two major elements that affect the overall acceptability of oral medicines, namely swallowability and palatability. The session started with presentations to provide an overview of literature, background and current state on swallowability and palatability assessments. Five parallel breakout discussions followed the presentations on each element, focusing on three overarching themes, risk-based approaches, methodology and product factors. This article reports the key outcomes of the workshop related to swallowability and palatability assessments.

Objectives Infusion of precipitate or destabilized emulsion can be harmful. The purpose of this study was to obtain Y-site compatibility data on intravenous drugs and total parenteral nutrition (TPN) relevant for children. Methods Two three-in-one TPN admixtures (Olimel N5E and Numeta G16E) used for children of different age groups were tested with ten drugs (ampicillin, ceftazidime, clindamycin, dexamethasone, fluconazole, fosphenytoin, furosemide, metronidazole, ondansetron and paracetamol). Drug : TPN ratios were estimated from a wide range of age and weight classes, and the most extreme mixing ratios (drug > TPN, TPN > drug) in addition to 1 + 1 were chosen. Assessment of potential precipitation was performed by subvisual particle counting, visual examinations and measurements of turbidity and pH. Emulsion stability was investigated by estimation of percentage of droplets above 5 μm (PFAT5), mean droplet diameter and pH measurements. Complimentary theoretical evaluations were performed. Key findings Ampicillin, fosphenytoin and furosemide precipitated when mixed with TPN. The results for ceftazidime, clindamycin, dexamethasone, fluconazole, metronidazole, ondansetron and paracetamol suggest that they were compatible with either TPN in the tested concentrations. None of the drugs were found to destabilize the emulsions. Conclusion Three drugs showed clear signs of precipitation when mixed with TPN and these products should not be co-administered in the same infusion line.

ObjectivesThe aim of this study was to investigate the use of off-label (OL) and unlicensed (UL) medicines to hospitalised children in Norway, to add to the current knowledge on use of medicines in this vulnerable patient group.MethodsThe study was performed as a cross-sectional prospective study. Medication was classified as on- or off-label based on the comparison with the SmPC regarding age, indication, dosage, route of administration and handling of the product. UL products were classified as imported or pharmacy produced.Key findingsMore than 90% of children receiving medicines in our study were given OL or UL medicines. More patients received OL (83%) than UL (59%). Route of administration was the most frequently observed OL category. The vast majority of the OL prescriptions were for ‘off-patent’ products. One-third of products prescribed were UL.ConclusionsThe study confirms that medicines to children in hospital to a significant degree are being used outside or without authorisation, in spite of recent paediatric regulatory initiatives. More data are still needed on efficacy and safety of medicines used in children, data to be incorporated in the SmPC. In addition, suitable formulations are needed to ensure optimal dosing and adherence without risky manipulations.