Entering New Domains for 3D Printing of Drug Products

By definition, three-dimensional (3D) printing is an advanced additive manufacturing technology where a computer-designed 3D object is created by consecutive layer depositions. While 3D printing of medications has seen one commercialized mass-manufactured product, the real opportunity for the technology lies in its ability to manufacture drug products at small scales (1). Positive clinical outcomes of treating patients with 3D-printed medicines have already been demonstrated in children affected by rare disorders (2,3). The technology has now been implemented into point-of-care facilities as well as major pharmaceutical company laboratories, and even NASA aims to tackle future medical therapy in outer space through 3D printing (4). Research has also shown how pharmaceutical 3D printers can be adapted as platforms for automation of medicine compounding to reduce production time and enhance product quality, and implications for early-stage development and first-in human studies are actively being explored by the pharmaceutical industry (5).

Several 3D printing technologies exist, with ones that are currently more clinically applicable including semi-solid extrusion (SSE), fused deposition modeling (also known as fused filament fabrication), and direct powder extrusion, due to their use of FDA-approved, generally recognized as safe excipients. These are already available in good manufacturing practice (GMP) grades and, with the continuous advancements in design, functionalities, and software of pharmaceutical 3D printers, they enable partially automated manufacturing processes. The flexible nature of 3D printing allows for a variety of implementation strategies, where certain scenarios are already realistically attained under current and emerging drug manufacturing paradigms.

Automated compounding strategy in pharmacies

Pharmaceutical compounding constitutes a small proportion of all administered solid dosage drugs and, in some countries, may be considered a technique of former times. Being a highly manual process, conventional compounding is prone to human errors leading to either over- or underdosing of drugs, while being less efficient than mass manufacture processes (6). Nonetheless, there is still clinical demand by many patients and patient groups (i.e., children) for medications not available off-the-shelf, such as differentiated doses and allergen avoidances (7). Although compounded medicines generally do not have to undergo FDA approval and be manufactured under GMP conditions, processes with tighter product and process controls are desired to yield better and safer clinical outcomes. Therefore, adopting novel technologies providing tighter and/or automated process and product controls could reinforce pharmaceutical compounding for better therapy and potentially increase its extent. A study of hospital pharmacy professionals has previously highlighted their positive views on implementing SSE 3D printing for compounding of medicines not commercially available (8). Although pharmaceutical 3D printing is considered an advanced manufacturing technology, the use of 3D printers to automate compounding workflows would already be possible in many countries under their existing guidelines.

Early in 2025, the world’s first study implementing a pharmaceutical 3D printer for compounding and dispensing minoxidil medications directly in a retail pharmacy was published (9). Minoxidil is used to treat different types of hair loss and is most commonly available in topical formulations; however, prescription and compounding of low-dose oral solid minoxidil medicines is common. Working under applicable compounding guidelines, capsules were automatically filled in two dose strengths using the SSE 3D printing technology available in the M3DIMAKER 1 3D printer in the community pharmacy in Madrid. In parallel, a traditional compounding procedure was used to prepare the same strengths of minoxidil capsules; the two methods were compared in uniformity of batches and resource requirements (i.e., labor and production time).

Using both in-house, prepared pharma-ink (drug-loaded formulations for 3D printing) compositions and commercially available, premade ones, it was shown how a pharmacist’s working time could be reduced at lower cost. Consistent flow of pharma-ink through the nozzle and mass uniformity assessment for each of the capsules was completed automatically and in real time through the integrated analytical balance and pressure sensor and healthcare software, enabling process monitoring and exact identification of out-of-specifications dosage units according to applicable limits. While both conventional and 3D printer-compounded capsules fell within the applicable mass uniformity specifications, the partially automated process using the 3D printer reduced the overall time requirements for manufacturing. A significant 55% reduction in time required for pharmacist involvement was observed, leaving much less margin for human-induced errors while liberating valuable pharmacist time. In connection with the in-line, automated mass uniformity assurance, this may be a real game changer for compounding of medications in pharmacies.

Rapid manufacturing process on-site enabling clinical trials in hospitals

The capsule filling approach by SSE attachment in pharmaceutical 3D printer M3DIMAKER 2 has also been implemented in the hospital pharmacy of Europe’s leading cancer research hospital, Institut Gustave Roussy, located in Paris (10). Here, the aim was to develop a process for manufacturing a large number of targeted pharmaceutical interventions in a suitable timeframe for a clinical trial in 200 cancer patients. The team of pharmacists demonstrated a process capable of manufacturing 200 multi-drug capsules in 45 minutes via the semi-automated compounding platform, which included time for pharma-ink manufacture and offline quality control. The manufacturing time may be significantly reduced in the future if pharma-inks could be supplied directly to the hospital pharmacy from a licensed manufacturer and through the integration of in-line quality control systems. The pharmaceutical 3D printers are also now used routinely to produce ‘traditional,’ layer-by-layer 3D-printed medicines in the hospital pharmacy under existing compounding regulations, to treat cancer patients through more tailored medications (11).

Distributed manufacturing strategy

3D printing of medications may fall under a distributed manufacturing scheme. Distributed manufacturing is often referred to as decentralized manufacturing outside the United States. Despite the difference in utilized terms, the two designations are paradigmatic and denote the same type of framework. In a distributed manufacturing strategy, one or more distributed 3D printing manufacturing sites (i.e., small manufacturing facilities) would be enabled by centralized pharmaceutical quality system (PQS) sites, similar to multiple spokes connected to a centralized hub in hub-and-spoke models (12) (Figure 1). Data transfer in real time between distributed manufacturing sites and PQS sites would enable close monitoring of data pertaining to drug product quality and the manufacturing process for dispensing of appropriate personalized medicines to patients. In a distributed manufacturing framework, pharma-inks may be externally produced with appropriate quality control measures at licensed manufacturing sites, akin to conventional pharmaceutical manufacture (13).

New legislation coming into effect in the summer of 2025 in the United Kingdom recognizes distributed manufacturing of medications through 3D printing. In the UK, the Medicines and Healthcare products Regulatory Agency has termed the process ‘modular manufacture’ with oversight of production activities at the self-contained modular manufacturing units by a centralized control site, similar to the previously described PQS site (14). Distributed manufacturing frameworks are still under development by FDA and the European Medicines Agency, but are expected to follow in the near future (15,16). Once finalized, these frameworks will officially mark the beginning of a new dimension for pharmaceutical manufacturing and personalized medications within their respective regulatory realms.

Conclusion

3D printing of drug products was once only seen as an alternative manufacturing technology for conventional large-scale manufacture. However, persistent efforts have more recently proven its applicability in producing small batches of tailored medicines. Clinicians and pharmacists alike have implemented 3D printing of personalized drug products under existing compounding regulations in both hospital and retail pharmacies, proving the approach’s benefits in terms of dosing accuracy and reduced manual labor. A new regulation coming into effect in summer 2025 in the UK will see 3D printing of drug products possible under a distributed manufacturing paradigm, and discussions for implementing similar frameworks in other independent legislative areas in other parts of the world are currently ongoing.

References

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About the authors

Anna Kirstine Jørgensen is a PhD student in the Department of Pharmaceutics, UCL School of Pharmacy, University College London. Alvaro Goyanes is a professor in the Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, honorary lecturer in the Department of Pharmaceutics, UCL School of Pharmacy, University College London, and co-founder of FABRX Ltd and FABRX Artificial Intelligence. Abdul W. Basit is a professor in the Department of Pharmaceutics, UCL School of Pharmacy, University College London and co-founder of FABRX Ltd.

Article details

Pharmaceutical Technology®
Vol. 49, No. 3
April 2025
Pages: 24–27

Citation

When referring to this article, please cite it as Jørgensen, A. K.; Goyanes, A.; and Basit, A. W. Entering New Domains for 3D Printing of Drug Products. Pharmaceutical Technology 2025 49 (3).