In the world of medical devices, not only the European market is important, but also the US market. That’s why it’s worth taking a closer look at the approval procedures there. The approval of medical devices is regulated by the Food and Drug Administration – the FDA. There are very specific regulations that must be followed to obtain approval, some may even say that the methods are more stringent and complex than in Europe – before the MDR is now in place. With this article we bring the necessary structure to the topic and provide all the important information.
The USA and the FDA – differences to Europe
The FDA is a federal agency of the United States Department of Health and Human Services. It is responsible for protecting and promoting public health. For this reason, the FDA controls the safety and efficacy of all drugs in human and veterinary medicine, biological products, medical devices and food. This applies to products manufactured in the U.S. as well as imported products. Therefore, all medical devices approved in the U.S. must be manufactured by a manufacturer that is audited by the FDA and complies with all of its regulations.
In general, there are quite a few similarities between the FDA and its regulations and Europe with the new MDR. Nevertheless, the U.S. has its own institution, namely the Food and Drug Administration, to control medical devices and their marketing. In contrast, Europe has an EU Commission regulation and separate so-called Notified Bodies. That’s one reason why the main effort of the two is different: FDA aims to prevent erroneous labeling and ensure holistic protection of medical devices, preserving their intended use, safety and efficacy. Europe’s main goal is to ensure the free trade and movement of medical devices within the European Union, but with a strong focus on product safety, quality and performance. By ensuring safety and efficacy in a balanced manner, the FDA system helps to ensure quality. For example, the European CE mark stands for safety, quality and performance based on risk assessment and clinical evaluation. The U.S. 510(k) stands for design equivalence to its so-called “predicate” (a comparable product already registered in the U.S.) based on intended use, and premarket approval for safety and performance based on clinical evidence.
In addition, the FDA is more focused on the quality management process and Good Manufacturing Practice to verify the quality of each product. Another important aspect is that the FDA performs audits itself, whereas the EU has Notified Bodies that must be certified as such in order to perform audits, or audits are performed by independent auditors. It represents a significant difference that in the U.S., almost everything about the process of approving a medical device comes from one institution, meaning that the FDA has both legislative and executive powers at the same time. In the EU, this is separate, as the EU Commission exercises the legislative powers and other institutions exercise the executive powers.
How to get FDA approval for your medical device
There are several approval procedures under FDA regulations. The four main approval processes are:
Premarket Notification 510(k) (PMN)
Premarket Approval (PMA)
Investigational Device Exemption (IDE)
Humanitarian Device Exemption (HDE)
Certain guidance documents can be used as a guide when preparing an application for submission. The Code of Federal Regulations – Title 21, which is part of federal law and consists of 50 sections, specifies how documents must be submitted to obtain approval. Title 21 is reserved for FDA regulations. Important sections are Sections 800 through 1299 – they deal with medical device regulations, Section 820 deals with the important topic of GMP (Good Manufacturing Practice).
Under this regulation, device classification is risk-based and determines the level of regulatory control. From Class I for low risk devices to Class III for high risk devices.
There are general methods of control such as electronic device registration, electronic device listing, quality systems, labeling, and medical device reporting. Specific controls consist of guidelines, mandatory performance standards, recommendations, and guidance documents. All of these control methods are used to ensure a smooth application submission process.
510(k) – Premarket Notification PMN.
If your product requires the submission of a Premarket Notification 510(k) (this term refers to Section 510(k) of the Food, Drug, and Cosmetic Act), you cannot commercially distribute it until you receive what is called a “clearance letter” from the FDA, which will then grant you clearance. A 510(k) must demonstrate that the medical device is substantially equivalent (SE) to a product that is already legally marketed commercially in the United States. It can be either a device that was approved before May 28, 1976, or a device that has been determined by FDA to be substantially equivalent. However, most Class I medical devices and some Class II devices are exempt from Premarket Notification submission. For additional and detailed information, please see our blog for another article that covers this topic.
Premarket Approval PMA
The PMA is the most stringent type of submission required by the FDA. Among other things, it requires scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Once the PMA is submitted, the review process begins and is divided into four steps.
Administrative and limited scientific review to determine completeness.
Comprehensive scientific, regulatory and quality system review
Review and recommendation by an advisory committee
Final deliberations, documentation and notification of FDA decision.
FDA will determine whether or not the application is complete within 45 days of receiving a PMA to initiate a detailed review. Then FDA will notify the applicant that the application has been submitted and accepted. This notification will include the PMA reference number and the date FDA recorded the premarket approval. Here, the filing date represents the date the PMA was accepted for filing and received by the agency. Therefore, the 180-day period for review of a PMA begins on the date of submission.
There are four types of PMA approvals:
Approval Order – PMA is approved:
FDA will notify the public of the approval. A summary of the safety and efficacy data will be posted on the Internet.
Approvable Letter – Conditional Approval:
Additional information is required that the applicant must provide or conditions that the applicant must meet in order to receive approval.
Not Approvable Letter (Not Approvable Letter):
Illustrates the deficiencies in the application. FDA will clarify what is needed to modify the PMA so that it can be approved.
Order Denying Approval (Order Denying Approval):
FDA may deny approval of a PMA if the applicant does not meet the requirements of the PMA regulation.
Investigational Device Exemption IDE.
The IDE allows the investigational device to be used in a clinical trial. This is an important step because clinical trials of high-risk medical devices must be approved by the FDA and an Institutional Review Board (IRB). Otherwise, the study cannot be conducted. For studies of medical devices of non-significant risk, IRB approval is sufficient.
Humanitarian Device Exemption HDE
The HDE allows a medical device to be approved without proof of efficacy, making it easier to place on the market. However, devices that fall into this category must be shown to have a positive impact on patients with rare diseases or conditions. In addition, the applicant must demonstrate that there is no other comparable medical device on the market and that this is the only way to market it. However, this type of approval is rarely used compared to the others.
The next steps
If your company has a medical device that needs to be approved for the U.S. market, you must first determine which of the approval options is right for you, and then proceed according to the defined process. Seleon gmbh can help you with its vast expertise, making FDA approval of your medical device more effortless for you.
Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.
