Guest Column | September 17, 2021

How To Build An Exceptional Medical Device Biocompatibility Program

By Jason Song, SureMed Technologies

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In recent years, biocompatibility and compliance with the ISO 10993 family of standards have been an area of significant attention for both medical device and pharmaceutical companies. Biocompatibility in itself is not something new; in fact, ISO 10993 dates back to the early ‘90s, prior to the FDA’s publication in 2016 of guidance on Use of International Standard ISO10993-1,Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” (updated in 2020), as well as the FDA’s Office of Device Evaluation (ODE) Blue Book Memorandum #G95-1 (1995). The renewed emphasis on biocompatibility may have resulted from global regulatory bodies’ recent attention on biocompatibility programs and more stringent review of biocompatibility studies and/or biological safety assessments. In addition, the recent implementation of EU Medical Device Regulation 2017/745 and the incorporation of biocompatibility requirements for medical devices and combination products such as drug delivery devices within the regulation further renewed attention to companies’ biocompatibility programs and strategies. 

Whatever the reason, demonstrating biocompatibility is an integral part of any device development and needs to be woven within the company’s product development process. Today, we hear a lot of concern about biocompatibility testing, approach, and strategy from both medical device and pharmaceutical companies. More often than not, these concerns arise because biocompatibility was assessed and seriously considered late in the development process, where there is no time or room to react to issues, deficiencies, or risks identified.

Before we dive into how to de-risk biocompatibility for any product development, I want to clarify that biocompatibility, in essence, is toxicology for medical devices and requires the biocompatibility scientist/toxicologist to holistically take into consideration a combination of biological and engineering factors, such as materials, the manufacturing process, physiological site and condition of exposure, and chemical interactions, to demonstrate user and patient safety. As such, the biocompatibility toxicologist, just like a quality engineer and other members of a product development team, should be involved and brought into the product development team early in the program, if not from the onset.

How To Integrate A Biocompatibility Toxicologist Into Your Team

The ideal background for a biocompatibility toxicologist should be a combination of both engineering and toxicology. This is because biocompatibility requires not only an understanding of toxicology and physiological responses but also the device and manufacturing mechanics, materials, and engineering. An essential job of a biocompatibility toxicologist on the project team is to help identify risks early and facilitate or help the team assess risks and alternatives.

Far too often, biocompatibility risks and/or gaps are identified too late in the program, often during or right after biocompatibility studies and around submission document writing. At this stage, the options for the project team are very limited and, in most cases, will require design changes or change control to the manufacturing process. Biocompatibility toxicologists with the combined engineering and toxicology background can help project teams avoid situations likes this by identifying risk areas and/or gaps and assess and propose or help determine alternative solutions during the design and development process, when the project teams have the necessary time and room to make adjustments.

At SureMed Tech, we are fortunate to have biocompatibility SMEs on our team who have dual engineering and toxicology degrees. As such, on many projects we could identify material and process chemical incompatibilities early in the development process and identify an alternative to the manufacturing chemical used, the process, or the product material, allowing for smooth and risk-free biocompatibility testing during design verification. In addition, we found that a biocompatibility SME with dual engineering and toxicology backgrounds can leverage both engineering and toxicology assessment/justification skills in devising strategies and approaches to resolve late-stage biocompatibility challenges for our clients, something that toxicologists or engineers alone may not be able to come up with. I am not advocating that you must hire someone with a dual background; what I am recommending is that to ensure biocompatibility program success, companies should ensure toxicologists recruited into a biocompatibility role also get a certain level of on-the-job engineering training so they can incorporate the engineering element as they develop the biocompatibility strategy. The opposite goes for engineers taking on the biocompatibility SME role – they should have some basic training on toxicology and toxicological assessments.

The Toxicologist’s Role Within The Product Development Process

To ensure a successful product development, a company should structure its product development process such that the biocompatibility toxicologist is integrated within the development team early on. As products may share similar materials of construct and/or overlapping manufacturing processes, the biocompatibility toxicologist can help the team to not only assess material and manufacturing process risks as it is being developed and avoid costly design and process changes later but can also help the team assess and identify strategic leveraging opportunities.

Early on, the biocompatibility toxicologist’s role is to help the development team assess and determine whether the selected materials are appropriate for the intended product and intended therapeutic use environment from a biocompatibility standpoint. As part of this, the biocompatibility toxicologist would also be able to help determine what and how applicable previous assessments and biocompatibility study results can be leveraged and utilized. This is especially so when it comes to labels for pharmaceutical drug delivery devices. By utilizing previously established biologically safe labels, the biocompatibility toxicologist can help alleviate a potential project team concerns during design verification and submission write-up. This can also help the packaging team standardize label materials and minimize retesting, especially in the case of pharmaceutical device development, where drug delivery device biocompatibility is often leveraged from vendor biocompatibility results.

In addition to helping with material selection, the biocompatibility toxicologist’s role is also to assist with manufacturing process development from the standpoint of product biological safety consideration. Process considerations from the biocompatibility toxicologist should not be limited to the internal assembly process but should be expanded to the component suppliers as well to ensure materials are not, for example, accidently exposed to situations whereby harmful byproducts may form -- such as overtemperature during a molding process. Here, a biocompatibility toxicologist can contribute to the overall control strategy of a product. Vendors of components that have well-controlled raw materials as well as released materials pose a low risk from a risk assessment standpoint and, as such, further contribute to the overall product control strategy.

During process development, the biocompatibility toxicologist should help the team identify appropriate processing chemicals that are safe not just for the product but also for the manufacturing personnel exposed to them. In addition, this will help the biocompatibility toxicologist develop an appropriate approach to demonstrate product biocompatibility as part of the biological assessment and leveraging assessment of the manufacturing process. This includes any chemicals used and potential residuals as well as process-derived byproducts. As such, during process development the biocompatibility toxicologist can assess chemicals used and any available biological safety/past biocompatibility data that can help shape the biocompatibility assessment plan and, if needed, allow the team time to adjust, as opposed to waiting until issues arise during design verification.

In Part 2 of this two-part series, I will discuss best practices to ensure biological safety and how to minimize risks when testing for biocompatibility.

If you would like to discuss this topic or have more specific questions related biocompatibility or biological safety (toxicology) assessment, please feel free to contact me directly. If you have any other topics or questions you would like to see covered or discussed, please drop a line in the comments section or reach out to me directly at

About The Author:

Jason Song, P.E., is chief technology officer of SureMed Technologies, Inc., a company he co-founded in 2018 that develops holistic novel technologies, products, and services that balance the needs of patients, industry, and the healthcare ecosystem. Previously, he held various technical and leadership positions at Amgen, Eli Lilly, GE Healthcare, Motorola, and Novo Nordisk in a range of areas, including injectable and inhaled drug delivery device development, fill and finish, packaging and assembly automation, biochips, battery development, and establishing new production sites. He holds BS and MS degrees in mechanical engineering, an MS in automation manufacturing, and an MBA.