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International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

SSE should be based on mathematical modeling, enabling forms with highly complex release kinetic profiles (e.g.,
adjustments of numerous variables to achieve desired different kinetics for different APIs) through a process
outcomes, such as specific dosages and targeted drug based on digital technology. The benefit for patients lies
release kinetics. Consequently, adopting the QbD approach specifically in the precision and flexibility of the products
is a key to the success of SSE in drug manufacturing. This manufactured, which can vary significantly from one
approach involves developing a control strategy defined patient to another. Given these factors, it would be
in ICH Q10 as “a planned set of controls, resulting from surprising if release quality controls were not implemented
the understanding of the product and the manufacturing for printed drugs, as the risks to patient safety and drug
process, which ensures the performance of the process and efficacy are substantial. Therefore, incorporating PAT into
the quality of the product.” The control strategy should 3D printers seems essential.
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ideally favor non-destructive quality controls conducted
“in line” during the manufacturing process. Such controls 3.1.3. Personnel
are technically through the use of process analytical Compounding requires qualified personnel with expertise
technology (PAT). PAT is defined in ICH Q8(R2) as “a in technical, scientific, and quality aspects. Drug AM via
system of design, analysis, and control of production SSE will require in-depth training to fully understand and
through the in-production measurement of critical quality master the technology. Specific training on the machinery
and performance attributes of raw materials and materials (particularly its use, control, cleaning, and maintenance)
in use, with the aim of ensuring the quality of the finished should be provided to all staff involved in this process.
product.” In essence, PAT enables the design, analysis, In addition, staff should also comprehensive training on
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and control of pharmaceutical manufacturing processes by slicing software that enables treatment customization to
measuring process variables, ensuring that they conform to ensure the quality and safety of the drugs produced.
the parameters set by mathematical modeling and that the 3.2. Manufacturing scenarios
quality of the finished product meets the expected standards. Currently, “traditional” compounded medicines are
The key advantage of PAT in the context of SSE is its ability manufactured at the point of care using pharmacy or
to provide non-destructive controls. This is particularly hospital staff and equipment (and regulated by section
valuable as the batches produced for each patient are often 503A of the Federal Food, Drug, and Cosmetic Act).
very small in size and may not be adequate for statistical Bearing in mind what has been said above, the crucial
analysis of the batch by representative sampling. For question is whether hospital premises and the staff who
instance, in the SSE process, pressure sensors integrated
into printers can measure extrusion pressure, facilitating work there can manufacture these SSE-printed medicines,
control of the drug’s quality attributes (e.g., dose, size, guaranteeing their safety, efficacy, and quality. We can
and weight). On-line near-infrared spectroscopy can be identify the following players involved in the development
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employed to quantify API content. Likewise, integrating and production of printed dosage forms.
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an in-built balance within 3D printers allows for precise The structure responsible for drug development follows
control over the mass of medicines manufactured. a Quality by Design approach, ensuring the development
of the drug formulation, the design of the 3D digital model
3.1.2. Regulatory aspects at the origin of the dosage form, and different calculations
From a regulatory standpoint, current regulations in and mathematical modeling allowing the prediction
both Europe and the USA do not require compliance of critical quality attributes of the product from input
with GMP, 135,139 as they are designed to regulate the variables. This structure will thus oversee defining and
mass manufacturing of standardized products. Hospital validating the production procedure, ensuring the quality
preparations are typically made in small batches for a of the process, its reliability, and its performance. In the
small number of patients. This approach allows for the remainder of this text, this structure will be referred to as
control of associated risks and ensures the maintenance “structure (a).”
of an appropriate level of quality. However, the FDA and
the French Medicines Agency have recently revised their The structure responsible for manufacturing the
quality recommendations, raising the required standards intermediate pharma-ink (the gel or paste placed in a
closer to those of GMP. cartridge or syringe, mixture of drug and excipients). In
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As a result, batch-release controls for compounding the remainder of this text, this structure will be referred to
are not required. However, the 3D printing of drugs at as “structure (b).”
the point of care may necessitate regulatory changes. AM The structure responsible for 3D printing is the
enables the production of highly sophisticated dosage pharma-ink, the post-processing, and the batch release.

Volume 10 Issue 6 (2024) 55 doi: 10.36922/ijb.4063