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International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

We have seen that generally post-processing consists of These scenarios are likely to coexist, depending on
a simple drying operation in the open air or in an oven. the hospitals’ ability to manage the development and
Freeze-drying is probably the most sophisticated drying manufacture of printed drugs. For a hospital, the use of
process found in the literature for SSE, but it remains little a third party for the development and/or manufacture of
used (see Table 1). This is why it is very likely that the pharmaceutical inks should be based on a risk assessment
structure that prints the drugs is the same as that which that will determine if the hospital can perform these
carries out post-processing. In the remainder of this text, activities while ensuring the quality, safety, and efficacy of
this structure will be referred to as “structure (c).” the printed medicine.
We can identify different scenarios for pharmaceutical
3D printing at the point of care, which are being considered 3.3. Applications of 3D printing technology in the
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by regulatory agencies such as the FDA or in other works compounding unit
such as Jørgensen et al. 141 Chronic conditions have been estimated to affect 10–30%
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of children, depending on the criteria used. Examples
Development and production at the point of care: In of chronic diseases include asthma, cystic fibrosis, HIV,
this first scenario, the hospital or pharmacy the hospital congenital heart disease, diabetes, attention-deficit/
would bring together the activities of structures (a), (b), hyperactivity disorder, depression, and cancer. For these
and (c). Printed medicines would therefore be developed, patients, as with adults, personalized medication based
manufactured, and distributed in the same way as other on genetic and physiological parameters is increasingly
compounded medicines made within hospitals. The feasible. However, this often requires adjustments to the
pharma-ink would be prepared at the point of care before treatment, risking non-adherence or sub/supra therapeutic
printing the medicines. This would imply a certain number effects. In many cases, it necessitates adapting the form
of constraints for hospitals, like maintaining qualified and strength of a licensed medicine. For example, in a
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personnel for ensuring the development of printed dosage phase I–II trial evaluating metronomic chemotherapy
forms as well as maintaining the equipment in a state of in patients with a relapsed or refractory Wilms tumor
qualification that ensures its operability and performance.
(MetroWilms), there was a need to administer adjusted
Point of care ensures only manufacturing of the final doses of cis-retinoic acid or etoposide. The dosage forms
product: the second scenario separates the development in the market did not accommodate these adjustments,
and production of the pharma-ink from the production of and patients were even required to drink an injectable
the finished product between two different structures. In solution of irinotecan due to the lack of an oral form for
this case, we could imagine that a pharmaceutical company the product. Changing the route of administration of a
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would bring together the activities of structures (a) and medicinal product is not a recommended practice, as it
(b), and oversee the research and development (R&D) for may have harmful consequences for pediatric patients.
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printed medicines, in collaboration with health authorities, Indeed, these practices may alter the efficacy and safety
3D printer manufacturers, and hospitals. Hospitals would parameters of the medication by modifying its absorption
only ensure that they manufacture the finished product. A characteristics, stability, and palatability. 31–33 For instance,
case study carried out by Seoane et al. and published in in the MetroWilms clinical trial, the etoposide injection
2023 studies the feasibility of decentralized production was unsuitable for children because it contained alcohol
of printed medicines in hospitals based on 3D printer
pharma-ink manufactured by a third party. On this and had an unpleasant taste, which significantly reduced
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basis, a pharmaceutical company could take on the task patient compliance.
of manufacturing the pharmaceutical ink and distributing To reduce this practice, hospital pharmacies are
it to hospitals. The commercialization of the pharma-inks currently producing various capsules and liquid forms to
may require the need for new regulations, as the pharma- meet patient needs with specific doses. As described by
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in is not a final medicine nor a raw material. Curti et al., compounding does not have high dose accuracy,
Outsourced development and manufacturing: An which is a problem for drugs with a narrow therapeutic
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alternative business model to the production of medicines index. With 3D printing, it is possible to manufacture
in a hospital or pharmacy would be one where the hospital medicines in more accurate doses for patients based on
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outsources the development and manufacturing of the their weight, age, and specific needs. The accuracy and
printed drug to a third party that would be structures (a), flexibility of 3D printing have been studied for low-dose
(b), and (c) all in one. The latter is a traditional industrial formulations for neonates and high-dose medications
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manufacturer subject to GMP or another hospital that has to reduce the number of tablets required. For certain
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the capacity to develop and manufacture the printed drugs. anticancer drugs or medications used in cardiology with

Volume 10 Issue 6 (2024) 56 doi: 10.36922/ijb.4063