As demand for personalised treatments grows, 3D printing is transforming pharmaceutical development with unmatched precision and adaptability. This shift away from ward-based manipulations of medication is especially vital in paediatrics, where accurate dosing and child-friendly formulations are crucial for safe and effective care, as Mattias Paulsson explains.
Medication-related harm has been recognised by the World Health Organization as a key global patient safety challenge. In 2017, it set an ambitious goal to reduce severe, avoidable medication errors by 50% within five years.1 While notable progress has been made in increasing awareness and adopting safer practices, the overall reduction in harm has not met the targeted decrease.
Licensed and approved medications meet established standards for safety and effectiveness. However, in many clinical settings, including hospital wards, a prescribed tablet strength may not be available, or a patient might have difficulty swallowing solid oral dosage forms. In such instances, the medication is often modified – by splitting, crushing or dispersing in fluids – at the point of care before administration.
Variation in medication manipulation practices and regulation
Medication manipulation practices vary widely between countries. For some, well-developed compounding services provide patient-specific doses within hours. In others, limited access, logistical challenges, or economic constraints make tablet manipulation a simpler, cheaper and more appealing option.
These differences often stem from the influence of pharmacists, regulatory policies and compounding structures. In Sweden, for example, non-aseptic compounding is centralised at a national facility, for which delivery lead times can exceed five days, thereby impacting its standard convention that hospital pharmacies can only provide medication for approximately three days.2
The first guideline on manipulation of drugs required in children was published over a decade ago. It combined evidence from a systematic review, an observational study on medication manipulation in neonatal and paediatric settings, and a UK-wide questionnaire of paediatric nurses.3
One of the guideline’s primary goals was to highlight to regulators, advisory bodies and the pharmaceutical industry that medication manipulations are a widespread practice, driven mainly by the lack of age-appropriate formulations. While the European Medicines Agency recommends that altering adult dosage forms for paediatric use should be a last resort,4 such practices are still common in many hospital wards.5–8
Highlighting the need for evidence-based formulations
A case report by Morris et al describes a serious adverse event involving the off-label use of prochlorperazine maleate tablets after the licensed liquid version was discontinued in the UK. The patient – a young child with a brain tumour – suffered uncontrolled vomiting after switching from the liquid to crushed tablets, resulting in multiple hospital visits and a prolonged stay.9
The solubility of the active substance in water is also crucial for achieving the intended concentration when a tablet is crushed and dispersed to obtain a smaller dose from a portion of the volume. Studies have shown significant variability in dose recovery when tablets are crushed and mixed with water, ranging from as low as 3% to as high as 99%.10 Depending on the salt form of the active substance and formulation, healthcare providers may not always have access to detailed solubility data.11
A recent narrative review provides a comprehensive overview of the challenges related to solubility, dose accuracy and clinical risks when manipulating oral dosage forms for children, highlighting the importance of understanding pharmaceutical properties before tablet dispersion or dose extraction.12
A ‘zero vision’ for medication manipulation
The concept of ‘Nollvision’, which translates as ‘zero vision’, originated in Sweden, primarily as a road safety philosophy aimed at eliminating fatalities and serious injuries. It has since been applied in other fields, such as workplace safety and healthcare.
As a strong commitment to safety and quality, a ‘zero vision’ where no medication manipulations are performed at the ward level could potentially be achievable if all medicines are delivered in ready-to-administer forms and administered in alignment with the Five Rights principles.
Thanks to the recent development of additive manufacturing tailored to hospital pharmacy needs, including clinical trials, the landscape for personalised medicines is rapidly changing.13–15 Unlike traditional compounding, 3D printing enables dose flexibility, rapid production and the incorporation of patient-specific parameters such as flavour, excipient profile and release characteristics.
A study by Rautamo et al investigated the perspectives of hospital pharmacy personnel on the usability of semi-solid extrusion printing in paediatric drug manufacturing.16 A qualitative approach was employed, utilising focus group discussions to gather insights. The participants included 43 pharmacists and pharmacy technicians from hospitals in Finland and Sweden, none of whom had prior experience with 3D printing technology.
To facilitate informed discussion, participants were first shown a demonstration of 3D printing of medicines. Participants found the equipment to be user-friendly and noted that it could enhance occupational safety by reducing exposure to medicinal powders. The technology was also recognised for its ability to produce personalised doses more precisely and efficiently than traditional methods, which could contribute to improved patient safety through better medication identification and continuity of treatment.16
Additionally, staff members expressed positive attitudes and a professional interest in the use of 3D printing in pharmacy practice. An added benefit identified was the potential to reduce medical waste in hospital wards.16
Building sustainability beyond the hardware
Establishing a sustainable infrastructure for personalised 3D-printed medicines requires more than just a printer. Hospitals must have access to pharmacopeial-grade active pharmaceutical ingredients and suitable excipients. For each product, formulation-specific parameters, such as solubility, taste and dosing range, must be considered early in the design process.
Unlike traditional compounded preparations, the digital nature of 3D printing allows flavouring and strength to be pre-programmed, making it possible to tailor drugs not only by dose but also by acceptability. This, in turn, requires structured documentation, such as dedicated fields in electronic prescribing systems, where prescribers can specify critical preferences like flavour, texture or excipient restrictions, to ensure that each patient receives a safe and personalised formulation.
To ensure safety and reproducibility, pharmacovigilance structures must be adapted to capture batch-level traceability and deviations.
At first glance, local production may seem financially burdensome. However, potential long-term savings could arise from reduced medication errors, improved patient adherence and decreased time spent by healthcare personnel on manual drug preparation. Moreover, hospitals can maximise the use of the production platform by applying it to clinical trials, treatments for rare diseases and compassionate use cases, thereby ensuring high utilisation and added value of the technology.
Conclusion
By transitioning from ward-level improvisation to digitally enabled, patient-specific manufacturing with 3D printing, hospital pharmacies can lead the way toward a future where medicines truly fit the individual, taking into account age, weight, formulation needs and preferences.
Author
Mattias Paulsson PhD
Deputy chief pharmacist, Uppsala University Hospital, and affiliated researcher at the Department of Women’s Health, Uppsala University, Sweden
References
1 World Health Organization. Global Patient Safety Challenge: Medication Without Harm. [Accessed July 2025].
2 Levine VR et al. Off-the-shelf medication transformed: Custom-dosed metoprolol tartrate tablets via semisolid extrusion additive manufacturing and the perception of this technique in a hospital context. Int J Pharm X 2024 Dec;8:100277.
3 Royal College of Paediatrics and Child Health. Manipulation of Drugs Required in Children (MODRIC) – A Guide for Health Professionals. [Accessed July 2025].
4 European Medicines Agency. EMEA/CHMP/PEG/194810/2005. Reflection Paper: Formulations of Choice for the Paediatric Population. [Accessed July 2025].
5 Johannesson J et al. Manipulations and age-appropriateness of oral medications in pediatric oncology patients in Sweden: Need for personalized dosage forms. Biomed Pharmacother 2022 Feb;146:112576.
6 Bjerknes K et al. Manipulating tablets and capsules given to hospitalised children in Norway is common practice. Acta Paediatr 2017 Mar;106(3):503–8.
7 Zahn J et al. Manipulation of Medicinal Products for Oral Administration to Paediatric Patients at a German University Hospital: An Observational Study. Pharmaceutics 2020 Jun;12(6):583.
8 Andersson ÅC. Manipulation of medicines, necessary in everyday practice for individualised doses in paediatric care. Doctoral thesis. Stockholm: Karolinska Institutet; 2023:75 pp.
9 Morris S, Salm V, Salm A. Harm to a child caused by the off-label use of prochlorperazine maleate tablets due to the discontinuation of licensed prochlorperazine mesilate liquid in the UK. Eur J Hosp Pharm 2024 Jun 14;ejhpharm-2023-003791.
10 Brustugun J et al. Adjusting the dose in paediatric care: dispersing four different aspirin tablets and taking a proportion. Eur J Hosp Pharm 2021 Mar;28(2):76–82.
11 Andersson ÅC, Nydert P, Paulsson M. Preparing paediatric medicines by dissolving tablets and extracting a portion may compromise dosing accuracy. Acta Paediatrica 2023 Aug;apa.16951.
12 Paulsson M et al. Challenges and Considerations in Manipulating Oral Dosage Forms in Paediatric Healthcare Settings: A Narrative Review. Acta Paediatrica 2025 Jul 2;apa.70199.
13 Sandler Topelius N et al. Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets. Pharmaceutics 2024 May;16(5):678.
14 Awad A et al. Reshaping drug development using 3D printing. Drug Discov Today 2018 Aug;23(8):1547–55.
15 Denis L et al. Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial. Int J Pharmaceut 2024 Aug;661:124306.
16 Rautamo M et al. Usability of semi-solid extrusion 3d printing in hospital pharmacy settings to produce personalized oral medications for pediatric patients. EAHP Congress 2024, Bordeaux, France: A43.
