Ahmed Zidan, Ph.D., Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research

Most drug products are typically manufactured in large quantities using conventional methods that involve large-scale processes, equipment, and long production time. Emerging advanced manufacturing technology may transform the way some pharmaceuticals are made. One such advanced technology is 3-dimensional (3D) printing. 3D printing can offer a tantalizing step toward changing the manufacturing processes to offer personalized medicines.

3D printing is a form of additive manufacturing in which a 3D object is built by depositing building materials in successive layers according to a predesigned 3D geometric structure. 3D printing of pharmaceuticals is a unique approach that allows for the manufacture of solid drug products in various shapes, geometric designs, strengths and spatial distributions of the active and inactive ingredients. 3D structures ranging from a simple one-compartmental design to complex multi-compartmental designs can be produced. The release profile of the active ingredients from these 3D complex drug products can be tailored to meet the needs of specific patients.

3D printing of drug products could offer several advantages for pharmaceutical applications. For example, it has the potential to produce unique dosage forms with characteristics that cannot be achieved in conventional dosage forms, such as instantaneous disintegration of an active ingredient, and other complex drug release profiles. To date, one FDA-approved drug—Spritam®--is manufactured using 3D printing technology. Spritam® tablets, for the treatment of epilepsy, are designed so that a large dose of active ingredient (1000 mg of levetiracetam) disintegrates within seconds after taking a sip of water.

Tailoring size, drug release profile and dosage form shape can be particularly useful for special populations with unique or changing medical needs. Children, for instance, may need special or smaller doses beyond what is conventionally available, or they may need unique dosage forms other than the standard pill, which can be difficult to swallow. Older adults may have various physiological or metabolic conditions due to certain illnesses or resulting from taking multiple medications, which may require alterations in doses or dosage forms on an ongoing basis. Moreover, it may be possible to combine certain medications into one “polypill” using 3D designs and 3D printing processes, which would be especially useful for those who take multiple medications every day. 3D printing of drugs offers these and other advantages because modifying a 3D digital design to control the performance of a drug product is easier than modifying physical equipment or process.

Addressing 3D Printing Questions Through Research

3D printing technology has been used to produce medical devices for nearly a decade, with about 200 FDA-approved 3D-printed devices available that can be tailored to fit a patient’s anatomy. Still, numerous questions remain about the use of this technology for drug products.

The Office of Testing and Research (OTR) in CDER’s Office of Pharmaceutical Quality is addressing some of these questions by conducting research to further understand the application of this technology to drug products. For example, we are working to understand the effects of material attributes, 3D geometric designs and 3D printing process parameters on the performance of 3D-printed solid dosage forms. In addition, we are trying to develop mechanistic models for 3D printing processes that can predict a drug’s performance in different patients. This research will enable FDA to answer key regulatory questions. For example, what are the critical parameters affecting the printability of various materials into drug products? What are the critical process parameters for each 3D printing technology? How can we assess the performance of 3D printed drug products? Can we use traditional in vitro testing methods for 3D printed drug products? How can we determine when and how a certain 3D geometric design may not perform as it should? What are the critical characteristics of the intermediate products for 3D printing, such as 3D printing inkjets, filaments, substrates and cartridges? What are the critical factors in 3D-printed design that affect the drug release rates and mechanisms?

In OTR’s state-of-the-art 3D printing facility, we are studying the behavior of the traditionally available excipients (inactive ingredients) of the conventional dosage forms during the 3D-printing processes, and discovering ways to best manage or control their behavior. For instance, the functions of commonly used inactive ingredients may not be applicable for 3D printing processes. We are looking to better understand these differences, and developing a “risk map” that can describe how the variations in material attributes and how they are processed may impact the quality, safety and efficacy of a drug product. We are analyzing these potential risks and determining the best way to mitigate them.

CDER is also considering the regulatory challenges associated with 3D-printed drug products, and to what extent the 3D-printing process may be controlled to ensure the quality of 3D-printed drug products. For example, the multiple components associated with 3D printing processes, namely 3D printers, printing materials, and intermediate products and processes, should be considered. CDER is working with our colleagues in FDA’s Center for Devices and Radiological Health to determine the best ways to approach these and other questions, while understanding that the technology is changing rapidly. As a part of FDA’s mission to ensure that safe and effective medications are available, we are helping to advance efforts on 3D printing of drug products while applying the same scientific rigor for safety and effectiveness that patients have come to expect from FDA.

The Spotlight series presents generalized perspectives on ongoing research and science-based activities within CDER. Spotlight articles should not be construed to represent FDA’s views or policies.