For Medical Devices
Assurance cases can reduce the time to market for products requiring regulatory oversight, for example, medical devices, while building a strong case for a product’s safety and effectiveness.
Assurance cases are a method for communicating the safety, effectiveness, and performance of a product by demonstrating how the submitted evidence supports the manufacturer’s claim.
Challenges of the Regulatory Process
When submitting a product for regulatory review, industry provides the regulating authorities with information such as clinical data, specifications, reports, and so forth. Regulators then analyze and review the data. This, then, leads to a regulatory decision.
Unfortunately, the reality isn’t as simple as it sounds.
One problem is that The FDA’s procedures and expectations are not always clearly defined. In addition, the pre-market approval process is expensive, and provides a high cost of entry for new products and companies. Finally, sometimes the manufacturer’s data themselves don’t make an obviously straightforward case for the manufacturer’s claims.
Bringing new products to market can, therefore, be costly and time consuming, and the regulatory system itself places numerous barriers between new products and the market.
Anatomy of an Assurance Case
An assurance case is a legal process that can help regulators to understand how the submitted evidence supports a manufacturer’s claim. This, in turn, can speed up the process of a regulatory decision.
An assurance case consists of the following parts:
Claim or claims about the product
Evidence supporting the claim
A detailed argument that ties the evidence to the claim
The argument structures and organizes the data such that the truth of each claim supports the truth of the next. This chain of supported claims in turn provides support for the theory and forms a straight line to the conclusion.
Infusion pumps were the subject of the FDA’s pilot program employing safety assurance case method in pre-market submission. A paper presented at the FDA’s 2019 public workshop FY 2019 Generic Drug Regulatory Science Initiatives provides an example of nested supporting claims regarding infusion pumps.
Main Claim: The design of the device is adequately safe for its intended use
Sub claim: Device requirements are adequate, and the device is adequately verified and validated
Sub claim: Risks associated with the device are completely identified and adequately mitigated
Sub claim: The device is adequately reliable to ensure safety over its use life
According to assurance case method, evidence supporting each of the sub claims builds a strong argument for the main claim.
Assurance Cases for Medical Devices
Assurance case method has a long track record in Europe, where it has been used in a variety of fields, including railway systems, avionics, military applications, and nuclear systems. The process came more recently to the United States, with the FDA being the first US regulatory authority to encourage the use of assurance cases in the evaluation of safety critical systems.
In the United States, the assurance case method has been used to demonstrate safety and cybersecurity for both standalone and combination products. Research continues to evaluate the method to address other concerns of the FDA, including justification for risk and benefit analysis conclusions and real world evidence validity.
Case Study: Infusion Pumps
Infusion pumps introduce nutrients, fluids, medications, and so forth, into a patient’s circulatory system. They’re in wide use around the world, both at home and in medical facilities.
In previous years, there had been a large number of adverse incidents involving infusion pumps reported to the FDA–56,000 reports between 2005 and 2009 alone. These incidents weren’t limited to products by a single manufacturer, or to specific types of pumps. Rather, the FDA found that they occurred across the board. As a result, the FDA issued 14 Class I recalls (where there was a reasonable probability that use of the device could cause serious, irreversible adverse consequences or death) and 87 Class II recalls (where there was a probability that the use of the recalled device could result in temporary or medically reversible adverse consequences).
In April of 2010, the FDA launched an initiative to improve the quality of infusion pumps, and to reduce the number of adverse incidents and recalls. Part of this initiative was a requirement for the use of safety assurance cases in pre-market submissions.
That same year, the FDA issued a preliminary guidance document for pre-market submissions of infusion pumps, aimed at both industry and regulators. The document looks at the total product life cycle for infusion pumps, and identifies device features that manufacturers should address throughout that life cycle. That guidance included a requirement for safety assurance cases.
In 2011, the Association for the Advancement of Medical Instrumentation (AAMI) offered its first course in the safety assurance case method. And in 2013, the FDA declared the safety assurance case pilot program for the infusion pump to be a success. Subsequently, in that same year, the FDA issued draft guidance for premarket submissions for management of cybersecurity for medical devices.
The final version of the FDA’s guidance document was released in 2014.
The infusion pump pilot program was considered a success for both industry and regulators.
Emerging Uses for Assurance Cases
In addition to device safety, assurance cases show promise in the areas of justification for risk and benefit analysis conclusions and real world evidence validity.
The FDA is currently investigating the use of real world data (RWD), and the real world evidence (RWE) drawn from RWD from electronic health records and medical claims data, to support regulatory decision making for both new products and off-label uses of existing ones. It’s proposed that this type of real world evidence could be used to support regulatory decisions without the need for conducting extensive clinical testing.
There are issues, of course, with this approach, including the fact that RWE isn’t as robust as clinical trials data. Data input may not be standardized across sources and may contain errors. Nonetheless, if done properly, this could help to speed lifesaving drugs, biological products, and medical devices to market.