# Global Regulatory Challenges for Medical Devices: Impact on Innovation and Market Access
## CE Marking
### United States of America
#### 4.2.2 Market Authorization  
All medical devices are subject to basic regulatory requirements known as general controls, which provide a reasonable assurance of a device's safety and effectiveness. As the risk associated with a device increases, additional regulatory requirements, such as special controls and premarket approval, are implemented [55; 56]. Section 510(k) of the FFDCA is a regulatory pathway used by the FDA to clear medical devices for market entry by demonstrating substantial equivalence to a legally marketed predicate device. This process requires manufacturers to show that their new device has the same intended use and technological characteristics as a predicate device, or that any differences do not raise new questions of safety and effectiveness. The 510(k) process begins with the submission of a detailed application to the FDA. This application includes a description of the device, identification of the predicate device, an explanation of the intended use and a comparative analysis of the technological characteristics of the predicate device [56; 57]. To expedite reviews for certain modifications, the FDA offers two alternatives to traditional submission 510(k): special 510(k) and abbreviated 510(k) pathways. These two forms were introduced to simplify and speed up the approval process for medical devices. Special 510(k) applies to modifications of a manufacturer's own legally marketed device, allowing for a more efficient review process for changes that do not affect the device's intended use or fundamental technology. Abbreviated 510(k) utilizes FDA guidance documents, special controls, or consensus standards to demonstrate substantial equivalence, thereby streamlining the review process [57]. Figure 7 compiles the three types of 510(k) submissions, as well as when each pathway should be used. For devices that do not have a substantially equivalent predicate device, manufacturers can pursue the _de novo_ classification pathway, where the FDA conducts a thorough review to evaluate the device's risks and benefits. This process is crucial for introducing innovative technologies or devices into the market that do not fit existing classifications [58]. The outcome of this review determines the device's risk classification (Class I, II or III). If  
Figure 7: 510(k) submission pathways: traditional, special and abbreviated [39]. classified as Class I or II, the device can be marketed immediately and may serve as a predicate device for future 510(k) submissions, enabling similar devices to follow a streamlined approval process. As mentioned, special controls are additional regulatory requirements imposed on Class II devices to enhance their safety and effectiveness. These controls can include performance standards, post-market surveillance, patient registries, special labelling requirements, pre-market data requirements and specific guidelines tailored to the device type [55; 59]. The PMA is the most rigorous pathway for FDA approval, focusing extensively on demonstrating the safety and effectiveness of the device through comprehensive scientific evidence. This includes detailed documentation of both administrative aspects and scientific research. The submission must adhere to strict regulations outlined in the FDA's framework, covering non-clinical research such as microbiology, toxicology and biocompatibility, as well as clinical research encompassing study protocols, safety data and patient outcomes. Consequently, manufacturers must meticulously prepare their PMA applications to address all regulatory requirements and scientific criteria. The failure to meet these standards can result in the denial of the PMA, effectively inhibiting the device from being marketed in the USA [55; 60]. Class I devices are subject to the least stringent requirements due to their perceived low risk [22]. These devices are not subjected to special controls and have no specific requirements.