The FDA’s Center for Devices and Radiological Health’s (CDRH) Office of Science and Engineering Labs (OSEL) is a part of FDA’s initiative to speed up medical device development and patient access to safe and effective medical devices by producing tools using innovative science in the assessment of new medical devices.
A Catalog of Regulatory Science Tools (RSTs) was developed by OSEL to expand the scope of science-based approaches used in the development of emerging medical technologies. These RSTs can be used by the industry to drive innovation and assess emerging medical technologies. The Catalog includes more than 100 RSTs, including laboratory methods, tissue-mimicking phantoms, and computational modelling and simulations.
These tools are intended to add speed and consistency to medical device development by streamlining the review process. However, the introduction to the Catalog states these RSTs do not replace FDA-recognized standards or qualified medical device development tools (MDDTs) since they have not been evaluated for suitability to any specific use.
OSEL conducts laboratory and field research in the areas of physical, life, and engineering sciences. Their collaborations with academia, health care providers, other government agencies and industry, support CDRH efforts to ensure public safety in areas as varied as medical imaging, medical device software, breast implants, and drug eluting stents.
In particular, their research program covers:
- Additive Manufacturing
- Artificial Intelligence and Machine Learning (AI/ML)
- Biocompatibility and Toxicology
- Credibility of Computational Models
- Digital Pathology
- Electromagnetic and Electrical Safety
- Emergency Preparedness
- Human Device Interaction
- Materials Performance
- Medical Extended Reality
- Medical Imaging and Diagnostics
- Microbiology and Infection Control
- Orthopedic Devices
- Patient Monitoring and Control
- Therapeutic Ultrasound
Tools that are recognized under the MDDTs are pre-qualified by the FDA and allow the sponsor to assess their product. This provides for more predictability in product evaluation by the FDA. The three categories of tools listed in the MDDT are:
- Clinical Outcome Assessment: Measures of how a patient feels or functions.
- Biomarker test: A lab test or instrument used to detect or measure an indicator of biologic processes or pharmacologic responses to a treatment.
- Nonclinical assessment model: A nonclinical test method or model that measures or predicts device function or performance in a living organism.
The MDDT qualification program is a complementary program for evaluating and recognizing tools that are useful for medical device evaluation and to support regulatory decision-making.
MDDTs have been qualified for cardiovascular, neurology, plastic surgery, automated insulin dosing, and imaging devices, as well as crosscutting tools for active implanted medical devices and cybersecurity. At the Regulatory Education for Industry (REdI) Annual Conference 2021, OSEL Director, Edward Margerrison stated, “regulatory science tools will grow up to become MDDTs once they have a defined Context of Use”.
RSTs reduce the need to design ad-hoc test methods and allow device developers to focus their limited resources on how well their new product works, not how well it may be tested. Validating ad-hoc testing slows the process of bringing innovative devices to market. It is therefore of great benefit to both innovators and regulators to use a common set of methodologies wherever possible.
The RST Catalog is organized into three categories: phantoms (i.e., materials that mimic the behavior of human tissues under laboratory conditions), methods, and computational models and simulations. Users can search for specific terms, sort results by field, or export lists to Excel spreadsheets. The tools are accompanied by references linking to scientific journal articles and/or user-end documentation, sometimes in the form of GitHub libraries.
One RST is the Virtual Family (VF), a set of four highly detailed, anatomically correct whole-body models of an adult male, an adult female, and two children. The four VF models are based on high-resolution magnetic resonance imaging (MRI) data of healthy volunteers. The VF models can be used for electromagnetic, thermal, acoustic, and computational fluid dynamics (CFD) simulations. Example of electromagnetic and thermal simulation applications are the assessment of the safety of active and passive medical implants in an MRI environment and the evaluation of the safety and efficacy of ablation devices. Acoustic simulations have been performed to assess the impact of the human anatomy on the focus location, shape, and intensity of ultrasound waves during focused ultrasound treatment. The VF 2.0 models are available at minimal charge to everyone.
Another tool is the Color Hazard and RISk calculator (CHRIS), which enables the user to perform rapid, screening level toxicological risk assessments of color additives that might be released from a coloured polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a provisional tolerable exposure value. The user inputs the following information into CHRIS: (a) the identity, amount, and concentration of a color additive, (b) the identity of the polymer matrix, and (c) three (3) medical device characteristics. The tool assists the user in determining (a) whether the toxicological risk of a color additive should be further assessed and/or (b) the potential impact of a color additive on device biocompatibility.
A joint initiative between CDRH and ECRI (Emergency Care Research Institute) led to published safety summaries for materials that are commonly used in implantable medical devices and the effects of those materials on patients over time. The summaries focused on several key questions, such as ‘Does the material elicit a persistent or exaggerated response that may lead to systemic signs or symptoms – beyond known direct toxicity problems?’ Some of the available material safety summaries include magnesium, polypropylene, PEG (polyethylene glycol), polyurethanes and silver. The FDA will continue to release safety summaries as they become available.
The RST Catalog will also be expanded and updated with new RSTs. By providing tools determined to be acceptable for the designated purposes, the FDA hopes to streamline the review process and concentrate its attention on the most critical aspects.
Although it reminds me of Q Branch from the James Bond films, the research and development division of the British Secret Service dedicated to developing cutting-edge tools, for agents to use in the field, OSEL and regulatory science tools represent an important contribution to reducing risk in all stages of product development and are particularly important to the early inventors and innovators, who often do not have the means to evaluate their systems. Innovators can now focus on producing a better device, not a better testing methodology.
Alexandra (Sandy) Reid is a StarFish Medical QA/RA specialist. She brings years of experience working in the industry. Sandy supports the QA/RA team in helping clients develop and deliver FDA Approved or Cleared Medical Devices.