'A clarion call for understanding regulatory processes for additive manufacturing in the health sector' by Antonia Horst, Fiona McDonald and Dietmar W. Hutmacher in (2019) 16(5)
Expert Review of Medical Devices 405-412 comments
As Additive Manufacturing (AM) in the health sector evolves to the point where products can be translated into the clinic, these manufactured goods need to be assessed by regulators in order for such products to be manufactured, sold, and used in accordance with the law. In this article, the authors argue that if AM products in the health sector are to be regulated in the near future, stakeholders involved in translational research need to understand the challenges faced by both regulators and industry. We portray different points of possible dissonance for AM medical products with existing regulatory frameworks. Hence, we advocate for stakeholders to proactively provide solutions for regulatory processes for products emerging from AM in the health sector.
The authors argue
The regulation of medical products emerging from additive manufacturing (AM) – the term associated with 3D printing in an industry context – in the health sector is an important milestone in the maturation process of the industry. Yet, new technologies often pose challenges for regulators who must determine whether a product is both safe and appropriate for use, as products that emerge from a new technology may (or may not) create different types of harms, risks, and areas of concern. These differences may also illustrate that existing regulatory regimes need to be modernized.
AM in the health sector is widely reported on in academic, as well as in industry or public media outlets, with manifold (potential) applications. Different applications of AM in the health sector are at different stages on their way to clinical translation: Products containing biological materials, such as cells or growths factors, are mostly at the research stage. On the other hand, some products manufactured through AM that do not contain biological materials are starting to be used in a clinical context and others are seeking regulatory approval. Such products include, for example, surgical equipment, prosthetics, hip and knee prostheses, implants, and other medical devices. These products show variety in their risk and complexity, ranging from low-risk devices, such as surgical planning models, to high-risk devices, such as biodegradable scaffolds (see Figure 1). AM is used to create standard sized (Figure 1), as well as personalized products (Figure3). Nonetheless, only a small number of these types of products are used routinely in clinical practice and have FDA approval and/or CE-Mark at the moment.
So far, a uniform vocabulary and clear terms have not yet been established to describe different product categories stemming from AM in the health sector. Nevertheless, a clear distinction between different kinds of products is essential when interfacing with regulatory structures, as different product categories may evoke different regulatory pathways.
While there is an ongoing discussion in the literature about terminology describing different categories of AM in the health and biomedical sector, so far no nomenclature has arisen that is universally accepted by the wider research community. We identify the use of different terms, or the use of the same terms with different underlying meanings, as a potential hindrance when interfacing with regulators. So far, unfortunately, there is a tendency in the literature to discuss ‘3D printing regulation’ or ‘Bioprinting regulation’ without a distinction to what is meant by these terms and which products they shall encompass. We, therefore, use the follow- ing descriptions to categorize the products that are intended for use in the health sector on the basis of the materials used in the manufacturing process: ‘AM in the health sector’ or ‘AM products’. These are used as broad terms, encompassing all aforementioned product categories. To allow for a more detailed discussion, we distinguish between AM containing biological matter in the manufacturing process, in other words, tissue engineered products manufactured using layer by layer techniques, and AM without the use of biological matter but for use in the health sector. This distinction is orientated by the regulatory separation of biological medical products, pharmaceuticals and medical devices, which will be discussed in more detail below. For clarity and simplicity, this article does not consider pharmaceuticals (see Figure 2).
Although the first AM products, such as biodegradable scaffolds (Figure 1), have been used for more then 10 years in a clinical context, they are only now being translated into routine clinical applications. One identified barrier to this translational stage is uncertainty about how the regulatory frameworks will respond to these new technologies. In academic and research-centered contexts, product regulation is generally not considered, as non-translational research folows different, more lenient sets of rules. Therefore, consumer safety laws, such as medical product regulations, are neither known of nor followed. Although start-up companies and industry are starting to engage with regulators and regulatory processes to understand what the industry could do to assist unobstructed regulatory processes, these considerations remain limited. While the need to interface with regulatory processes is becoming more pressing as industry interest in such products is rising and AM in the health sector matures, there is still uncertainty about when and whether some aspects of AM containing biological matter will get to the stage that they require regulation and even if they will at all.Opinions range from doubting whole organs will ever result from AM processes, predicting ‘printed organs‘ within the next few decades, to describing AM technologies for printing materials containing biological matter as if they were ready for commercialization and routine application in hospitals. This broad range of published viewpoints may result from overly optimistic and sometimes not evidence based reporting by researchers. This conclusion is drawn from the relative abun- dance of appraisals for these applications in the academic literature and wider media, compared with the lack of scientific evidence of such outcomes. Regarding AM products that do not contain biological matter, opinions around the feasibility of this technology to be upscaled as well as what the actual benefits of using this technology may mean in regard to patient recovery, health-care savings, and product development, differ significantly. These uncertainties create further challenges for an industry that needs to urgently prepare for regulation.
In this article, the authors argue that if AM products in the health sector are to be regulated in the near future, those involved in translational research and the manufacturing process need to understand the challenges faced by regulators, such as the US Food and Drug Administration (FDA) or the Australian Therapeutic Goods Administration (TGA) when dealing with new technologies. The academic and industry stakeholders involved in this area also need to understand the risk profile of the product class or products and their status as being mass produced or customized/personalized. The terminology must be used consistently and standards need to be designed with regulatory processes in mind so that they can function as a logical extension of regulatory processes. We advocate for the wider industry anticipating and being ready with solutions for regulators when they need to adapt regulatory processes to regulate products emerging from AM in the health sector.
