EMA issues guidance on GMP considerations for additive manufacturing
The European Medicines Agency (EMA) has provided guidance to help manufacturers adhere to good manufacturing practices (GMPs) when using three-dimensional (3D) printing technology, also known as additive manufacturing, in the production of solid oral dosage forms.The guidance states that 3D printing (3DP) is a broad term that encompasses various printing technologies used to create solid structures by layering materials. These dosage forms are produced from a digital 3D file, such as a computer-aided design (CAD) drawing.
“The 3DP technology can benefit finished product design by facilitating patient-centric treatment and by developing personalised medicines with e.g. a wide spectrum of dosage levels, shapes, flavours, colours, or drug combinations, all tailored to the specific needs of each patient or disease condition. These characteristics make this technology particularly advantageous for diverse patient groups, including paediatrics, geriatrics, those on multiple medications, and individuals with rare diseases,” EMA wrote.
Additionally, 3D printing can incorporate rapid manufacturing techniques using compact equipment, fewer production steps, automated and digital processes, and faster changeovers, particularly to produce small-scale solid dosage forms, said EMA.
Recent examples in Europe highlight the use of 3D printed tablets in hospital pharmacy settings, as reported in an article published on 25 December 2025, in the International Journal of Pharmaceutics. For instance, researchers at the University Medical Center Hamburg-Eppendorf have developed chewable, child-friendly dexamethasone tablets designed to prevent nausea and vomiting associated with chemotherapy. Additionally, at Vall d'Hebron University Hospital in Barcelona, chewable hydrocortisone formulations were created for a clinical study involving children with adrenal insufficiency.
The guidance outlines the quality requirements relevant to the use of 3D printing in pharmaceutical manufacturing. It also discusses process validation and the implementation of a control strategy.
In terms of quality, the guidance indicates that the following factors may affect product and process performance, depending on the technology and printer used: rheological properties and the extrudability/printability profile of the formulation being printed; the physical state of the active substance within the printed dosage form, whether crystalline or amorphous, and its impact on dissolution or pharmacokinetic behavior; the particle size of the raw materials; and the compatibility of the active substance with the excipient.
Further, the guideline notes that “the impact of the 3DP technology and the manufacturing process on the properties of the finished product should be evaluated.”
The guideline states that cartridges and syringes are “critical components” of the manufacturing process. As such, the stability of the formulation within the cartridge or syringe should be studied. Manufacturers should ensure that the storage within the cartridge have no impact on the stability of the finished product.
For multiple uses, the physical-chemical and microbiological stability, both before and after opening, should be assessed through in-use studies that reflect the intended use of the cartridge, including the number of re-uses and the appropriate storage conditions.
The guidance states that manufacturers should validate their validation processes for 3D printing. Sponsors should adhere to the EMA guideline on process validation for finished products. Whenever technical changes are made to the equipment, it is important to assess the relevance of previous validation studies. Additionally, the need for re-validation studies should be determined through a thorough risk analysis.
“In case the validation is carried out at the level of the ink manufacturer/printer supplier and the technology is transferred to the end user, the end user should demonstrate the robustness and reproducibility of the process by manufacturing a justified number of confirmatory batches (see question on GMP requirements for further guidance),” EMA wrote.
Manufacturers should implement a control strategy to ensure product consistency, quality, safety, and efficacy. This strategy must clearly define the specifications for the release of both the pharmaceutical ink and the finished product. Furthermore, these specifications must comply with the relevant guidelines set forth by the EMA and the EP monographs.
The guidance specifies that the following activities must comply with GMP requirements: equipment design, qualification, validation (including 3D printing software), the manufacture of intermediate cartridges and syringes, the printing process, quality control testing, and batch certification and release.
Guidance
