James Pink

Currently a $4-billion market primed to grow to $20 billion within the next decade, additive manufacturing (AM) for medical device applications is a rapidly growing field that is unlikely to slow down any time soon. That’s because it’s enabling manufacturers to produce complex medical devices and components from polymeric, metallic and other exotic materials more cost-effectively and quickly than with many traditional processes.

Applications within “commercial capability” now include patient-specific orthopaedic instrumentation; maxilla-facial, cranial and dental implants; and preoperative planning and simulation aids that entail reconstruction of patient regional anatomy from CT and MRI scans. And an increasing number of investors, academia, healthcare providers and manufacturers are continuing to develop new applications and prototypes for the technology at a breakneck speed.

The concern is, however, that as we expand into the medical technology arena, we do so with more “risky” applications at a pace at which the science may not corroborate the art. In addition to the fact that these products are custom-made and therefore not easy to regulate under current worldwide regulatory frameworks, there are very real product safety risks that need to be taken into account.  

The Benefits of AM
From a design perspective, opportunities in additive manufacturing are often centered on the customisable aspects of product design for individualised patient anatomy. This is generally achieved through the combination of imaging, establishing CAD models and postprocessing software to interact with a printer that will undertake the final 3-D printing of the product. Evidence is emerging that further benefits are derived from the actual joining technologies associated with AM; early evidence from the aerospace industry supports the possibility of beneficial mechanical properties of AM components in certain materials.

From a manufacturing perspective, AM is considered a “clean” process, with opportunities for almost silent, contained, highly environmentally controlled manufacturing. In the medical technology area, contact materials used during the manufacture of product and the complexities caused by costly and environmentally unfriendly detergents are a specific area in which AM could present a solution.

The Risks of AM
In 2015, there is very little independent scientific and technical data available to corroborate technical safety in regards to additive manufacturing. Even when data is available, safety and performance requires standards, validation science and accurate test methods. However, there is a distinct lack of international collaboration within the medical technology realm on that front.

These facts present a clear problem for companies wishing to commercialise AM medical products when moving into higher-risk categories of devices. In light of this issue, the technical community needs to address how it can underpin AM in medtech with the necessary science. Positive steps are being made to do so, however, led primarily by industry and FDA. In October 2014, FDA held a workshop specifically discussing the application of AM to medical technology products and generated a list of specific areas where AM products require regulatory science answers.

Converting a Patient Image to a Solid 3-D Printed Model
In order to successfully convert a patient image to a 3-D printed model, software is required to ensure that there are no specific conflicts within the image and to convert the images into a solid model that can be processed by the multiaxis printer.

For reconstruction of a patient image for printing purposes, the manufacturer will to have to demonstrate that the software has accurately converted the image data into the solid model. It will also have to confirm that the printer software has rendered and processed the coordinates to lay-up the material in a reliable and reproducible manner.

The Sunday Times recently reported that a team at St. Thomas Hospital, London. had successfully 3-D printed a model of a heart from a toddler suffering from a hole in her circulatory system. The motivating factor behind printing the bodel was the small size of the anatomy coupled with the need for surgeons to determine the optimal technique for placing gauze to effectively repair the defect, thus reducing the risk of complication during surgery. The 3-D model ultimately enabled the surgical planning team to effectively rehearse the operation and iron out any specific issues or concerns before theatre.

This story is a wonderful example of the benefits of additive manufacturing and its potential to improve patient care. But from a product safety perspective, it is important that we challenge whether the software is technically robust enough to reliably and repeatedly produce these models if this technique is to be used in intricate surgery routinely and via commercially available solutions. Consider the possibility of a less favourable outcome in the future, for example, in which the surgeon is being sued due to patient injury or death because the AM heart he or she preoperatively planned was not adequately representative of the patient’s heart in vivo.

In regulatory terms, the software requires validation. The complexity of the validation increases the more accurate and precise the model needs to be.  Stakeholders in AM therefore need to ensure that there are consistent expectations for the validation of this type of software. Furthermore, professionals involved in commercialising these technologies need to ensure that guidance and acceptance criteria are defined in this area.

Materials
The term medical-grade material has been used for several decades; however, we understand that the concept of biocompatibility is more important than medical grade. For instance, although the 3-D printing material may be identified as medical grade, the finished component, its packaging and the sterility method employed are all a function of its chemical and mechanical characteristics when it interacts with a human. This can change dramatically by the mere nature of the duration, type and intended purpose for which the finished product will interact with the patient.

Evidence from aerospace studies has already identified that the properties of 3-D printed materials are different than those properties found in materials processed via extrusion, moulding, casting and other conventional forming technologies. The slight variations in those properties can affect mechanical integrity, chemical integrity and the biocompatibility of the medical part.

Manufacturers also need to understand the effects of printing different forms and features with different materials and their binding agents, in addition to the ramification on the properties of those materials. Equally important are the less known properties—physical and surface chemistry, for instance—and how they affect biological processes.  Manufacturers must gain assurance that the surfaces are still performing in a biocompatible way as intended—whether inert or bioactive, for example.

Standards are well established for implant-grade materials; however, the powders and joining methods are not substantially equivalent to metals in cast and wrought forms, for example. Further scientific review and research is thus required to suitably gain confidence as to what the limits are for printed implantable-grade materials.

Specific Product Validation Requirements

Cleanliness, sterility and packaging processes are all considered special processes that require a specific, internationally accepted series of studies to demonstrate that the product will be free from contaminants and unintended organisms and that it can withstand storage and transportation factors. The processes are a function of the shape, manufacturing process and environmental conditions of the product as well as the design of the cleaning, sterilisation and packaging processes.

Ultimately, the individualised nature of additive manufacturing products may have significant effects on maintaining validated process parameters. Consequently, during the design, you may find that the validation methods are vastly different from those of routinely manufactured products.

Guidance and standardisation are required for product validation activities associated with additive manufacturing, and the industry needs to collaborate in order to establish this guidance or adopt industry norms. What is clear, however, is that current standards, guidances and practices do not address the custom nature of these products. Therefore, any considered “safe scientific approach” will need to take into account the individual variables associated with AM products. Of course, doing so may require some intricate science, intricate parametric modeling and simulation—or, frankly speaking, a much larger and varied sampling rationale when validating products.

Process Control and Product Release
Process validation is a tool used within the medical device industry when it is not easy to fully verify through inspection that product characteristics have been achieved. A medical device product specification includes process limits and controls that, when validated, mean that features such as mechanical integrity, fatigue, chemical degradation and sterility can be estimated with a high level of confidence.

The single, custom-made nature of AM products—including subsequent cleaning, packaging and sterilisation process parameters—are such that it may be difficult to demonstrate that changing the size and shape of an implant, for instance, will not drastically affect the degradation of the implant through fatigue or other means.

Establishing standard methods of inspection and test systems, including the development of nondestructive technologies for AM products, should be considered. These methods will need to be internationally accepted within the global medtech industry.

Summary
Additive manufacturing and 3-D printing are generating a great deal of excitement in the medtech community for their potential to improve patient outcomes. However, it is imperative that these innovations are firmly supported by scientific knowledge and safety considerations. Consider the recommendations and discussion points presented in this article when commercialising your AM solution to ensure that you have the necessary science to corroborate your art.

James Pink is the medical devices, vice president at NSF Health Sciences.

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The Sunday Times, UK (subscription required). (2015, January 25). Little Mina saved by 3D printer heart. Retrieved February 2, 2015, from The Sunday Times: www.thesundaytimes.co.uk