US FDA Expectations Overview

By Sarah Fitzgerald

Medical device regulators around the world are encouraging coordination and regulatory consistency. From a high level, virtually all medical device regulators take a risk-based approach and require that the benefits of the medical device outweigh the risks before authorization. However, detailed expectations are not yet consistent. Manufacturers from other regions are often surprised by some of the differences in expectations from the United States (US) Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) as compared to other regulators. 

Overview of medical device classification

Medical devices for human use are classified by a three-tiered system (Class I, Class II, and Class III) that is based on risk and therefore, the level of regulatory controls (i.e., general or special) deemed appropriate for the risk posed by the device. Classification is determined by matching the device description and use to a corresponding 3-letter ‘Product Code’ and a 7-digit ‘Regulation Number’ specified in 21 CFR Parts 800–1299. The FDA Product Classification Database may be used to match key search terms to potential product codes. 

Most Class I devices, or low-risk devices, only require general controls and are premarket-submission exempt, meaning that a specific submission to the FDA is not required before selling the device in the U.S. Some require a premarket notification, or 510(k). 

Most Class II devices, or moderate-risk devices, require both general and special controls and a 510(k), to be submitted and cleared by the FDA before selling the device in the U.S. Some are 510(k) exempt. 

There are two main types of Class III devices, high-risk devices and novel devices considered automatic Class III devices. In both cases, clinical trials are generally required to provide the FDA with adequate assurance of safety and effectiveness. High-risk Class III devices usually require a premarket approval (PMA) before selling the device in the US. Some may require a 510(k). Automatic Class III novel devices may require a De Novo, requesting categorization of the device into Class I or Class II and marketing authorization from the FDA. 

Every medical device sold in the U.S. must meet a set of requirements corresponding to the device classification and be listed with the FDA. For any device that requires a premarket submission, like a 510(k), the FDA will review certain information before authorizing the device for the U.S. market. 

Overview of CDRH expectations in premarket submissions

CDHR has both general expectations and special considerations. In general, a company should first ensure that they have relevant portions of a Quality Management System (QMS) implemented and then conduct a risk assessment in alignment with ISO 14971. They should establish a plan for evaluation including validation and/or verification testing. The FDA recognizes many consensus standards, which can be searched here. Additionally, the FDA publishes their own guidance documents, some of which are related to broadly applicable subjects (such as electromagnetic compatibility [EMC]) while others are product specific (such as for dental bone grafting materials). However, not all topics are covered. Furthermore, the FDA considers all guidance documents non-binding and frequently asks for information that is not clearly indicated in guidance documents or standards. Specific special controls that the FDA expects to be addressed may also be listed in the applicable regulation for the device. 

Many expectations are the same or similar for other major regions in the world. However, some are significantly different. This can be very frustrating for a manufacturer trying to enter the U.S. market. 

Overview of general FDA expectations that are frequently considered significantly different 

There are three main general areas where the FDA frequently has expectations that are significantly different from most other regions of the world. These areas are biocompatibility, reprocessing (cleaning, disinfection, and/or sterilization) and cybersecurity. Details on these will be provided in the three subsequent articles. 

In addition to the areas above, it is important to note that the FDA considers there to be potential demographic differences that must be carefully considered when usability / human factors and/or clinical validation is necessary. Most regions do expect a manufacturer to address this, so this is not strictly a different expectation, but it can lead to the need for additional testing. Therefore, a company should carefully consider conducting such testing in the U.S. when the U.S. is the target market to reduce the chance of rejection. 

Minimizing risks of FDA rejection

There are several ways to minimize the risk of not aligning with the FDA. 

First, a manufacturer must determine the appropriate regulatory classification and pathway to bring their device to market. This includes determining the product code and regulation number. If this cannot be determined with certainty, a 513(g) or a Request for Designation (RFD) may be utilized to align on this basic regulatory information. 

Second, a manufacturer should carefully consider whether the evaluation and testing that they have conducted is in alignment with FDA guidance documents, both on general topics and on relevant specific topics, and any special controls for the device type (which may be provided in the regulation number). 

If a manufacturer has questions related to the acceptability of their data, even data that has been accepted by other regulators as sufficient, they may wish to consider formally reaching out to the FDA via a Q-submission to obtain FDA feedback. It is important to note that a Q-submission is not intended to be a pre-review of a submission, but rather to obtain feedback and alignment regarding higher-level topics. It is acceptable to summarize the evaluation and testing and ask for FDA feedback. Emergo experts specifically recommend submitting a Q-Submission to the FDA before conducting any animal performance or clinical testing and considering such a submission any time there are questions related to testing that is costly and/or takes a significant time to conduct to reduce the chances of the testing being found insufficient to meet FDA expectations. 

Note that if conducting certain clinical testing with significant risk, a submission called an investigational device exemption (IDE) will be needed to permit the clinical study on the otherwise unauthorized device. 

Only after the manufacturer has reasonable confidence that they are meeting FDA expectations including related to verification and/or validation testing should the premarket submission be made. Note that even then, during the review of a premarket submission the FDA frequently asks questions related to what they consider potential deficiencies. These need to be addressed. 

Concluding remarks 

Medical device regulators around the world attempt to protect their people by ensuring that they only authorize products where the benefits outweigh the risks. However, there are different expectations and even a device that has been authorized in other regions may not have the full information considered necessary to meet US FDA expectations. 

The main areas of increased U.S. FDA focus compared to many other regions are biocompatibility, reprocessing (cleaning, disinfection, and/or sterilization), and cybersecurity, which will be discussed in subsequent articles. 

Manufacturers are recommended to carefully consider FDA guidance on all topics and to request a formal meeting with the FDA through the Q-Submission process to align on expectations prior to conducting costly or time-intensive testing.