Medical Devices Regulatory Overview in USA
The responsibility for overseeing the regulations of medical device companies involved in the production, repackaging, relabeling, and medical device registration in USA falls under the jurisdiction of the FDA's Center for Devices and Radiological Health (CDRH). The rules established by the US Food and Drug Administration pertaining to medical devices and products emitting radiation can be found in Title 21 CFR Parts 800–1299, subchapter H of the Code of Federal Regulations (CFR). These definitive regulations, codified in the CFR, encompass a wide range of aspects related to medical device development, clinical assessment, manufacturing, packaging, labeling, and post-market monitoring.
Local Representation Requirements
The US Food and Drug Administration (FDA) mandates that all medical device and in vitro diagnostic (IVD) companies operating without a physical presence in the United States must appoint a registered local representative within the USA. This designated representative is commonly referred to as the "US Agent." To fulfill this requirement, the US Agent m
ust either be a US citizen or have a physical office within the United States. While the foreign institution has the option
to appoint its US Agent as its official correspondent, this selection is not compulsory. The foreign establishment is
responsible for providing the name, address, phone number, fax number, and email address of the US Agent as part of this regulatory obligation.
Classification of Medical Devices
Medical devices are categorized into three classes: Class I, Class II, and Class III, with the classification determined by the level of associated risk. As one progresses from Class I to Class III, the degree of risk increases, leading to more rigorous regulatory oversight. It's important to note that In Vitro Diagnostics (IVDs) and Software as Medical Devices, also known as Digital Health Devices, do not have distinct classification systems; instead, they adhere to the same fundamental principles for classification.
Medical Device Registration in USA
Class I Medical Devices: In many cases, Class I medical devices do not require prior FDA approval and are often exempt from compliance with Good Manufacturing Practices (GMP) and the submission of a 510(k). Although these devices are exempted from the need for medical device registration in the USA, medical device manufacturers must still adhere to general requirements, such as Medical Device Establishment Registration, Medical Device Listing, Unique Device Identification (UDI), Post Market Surveillance (PMS), and others. It's worth noting that for the majority of Class I devices, the submission of a Premarket Notification 510(k) is not mandatory, unlike the requirement for the majority of Class II and Class III devices.
Class II Medical Devices: These are medical devices with a moderate level of risk that, if they have predicate devices approved through the 510(k) process, have the option to register under the 510(k) regulatory framework via a 510(k) Pre-market Notification (PMN). To utilize this route, it is essential to demonstrate Substantial Equivalence (SE) between the device in question and the predicate devices that have been identified and asserted. In the United States, this approach is the most commonly chosen method for device registration. However, manufacturers of moderate-risk devices that lack predicate devices can opt to submit a De Novo classification request to the US FDA.
Class III Medical Devices: Manufacturers of medical devices classified as high-risk in Class III are required to secure advance approvals from the US FDA before they can introduce the medical device to the US market. In order to obtain this approval, manufacturers must provide extensive data on the safety and effectiveness of their devices, including results from clinical studies and a thorough evaluation of the device's clinical performance. As part of the evaluation process leading to the granting of Pre-Market Approval, the US FDA conducts inspections of the device manufacturer's Quality Management System (QMS).
Pathways for Medical Device Registration in USA
Premarket Notification or 510(k) Registration
A 510(k) submission is required to demonstrate that the device is substantially similar to either: (1) a device that was legally available for commercial distribution in the US before May 28, 1976, or (2) a device that the FDA has already determined to be substantially equivalent. It's important to note that Pre-Market Notification 510(k) submissions are not obligatory for the majority of Class I devices or certain Class II devices. A list of devices that are exempt from 510(k) requirements can be found under "510(k) Exempt Devices."
For those planning to submit a 510(k) application to the FDA for a Class I or Class II device, it may be beneficial to consider a 510(k) review conducted by Accredited Persons. The FDA has accredited 12 entities to conduct initial assessments for 670 different device types. According to the law, the FDA must make a final determination within 30 days of receiving a recommendation from an accredited person. It's worth noting that while the third party may charge a fee for their evaluation, the 510(k) review conducted by an Accredited Person is exempt from any FDA fees.
Premarket Approval (PMA) - 21 CFR Part 814
Products requiring Premarket Approval (PMA) are categorized as Class III devices, denoting them as high-risk products with a significant potential for causing disease or injury. Alternatively, they may include products that the 510(k) process has determined to be not substantially similar to Class I and II predicate products. The PMA procedure encompasses multiple stages and necessitates the provision of clinical evidence to substantiate the claims made regarding the device's performance. Beginning with the fiscal year 2003 period (October 1, 2002, through September 30, 2003), Premarket Approval Medical Device User Fees are applicable to initial PMAs and specific types of PMA supplements. Small companies may qualify for fee reductions or waivers.
Employing an investigational device in clinical research to collect safety and effectiveness data for either a Premarket Approval (PMA) application or a Premarket Notification 510(k) submission to the FDA is allowed through the utilization of an investigational device exemption (IDE). However, prior to commencing clinical research involving a device with a substantial risk, approval from both the Institutional Review Board (IRB) and the FDA is required. In contrast, studies involving low-risk devices only necessitate approval from the IRB before the trial can commence.
The De Novo Classification
The De Novo request provides a pathway for classifying innovative medical devices. These devices can be classified under general controls alone or in combination with special controls, which collectively ensure a reasonable level of safety and effectiveness for their intended use. However, this classification applies when there is no legally marketed predicate device available. Medical devices that obtain a Class I or Class II classification through a De Novo classification request (De Novo request) can be marketed and, when applicable, used as reference points for future premarket notification [510(k)] submissions.
The quality system regulation encompasses guidelines governing the processes involved in the design, acquisition, manufacturing, packaging, labeling, storage, installation, and maintenance of medical equipment, along with the associated facilities and controls. FDA inspections of manufacturing facilities serve to verify compliance with these quality system standards.
With the exception of products exclusively distributed within Puerto Rico or a U.S. territory where a language other than English serves as the primary language, all labeling must be in English. In certain cases, English may be substituted with the predominant local language.
The license remains in force unless there is a substantial modification to the medical device. Annual renewal of establishment registrations is mandatory. Manufacturers are obligated to pay the Annual Medical Device Establishment Fees annually, occurring between October 1st and December 30th.
Post Approval compliance Requirements
Establishment registration 21 CFR Part 807
The FDA mandates that both domestic and international manufacturers of medical devices, as well as the first distributors (importers), must complete the registration process for their operations. Unless the FDA has granted an exception, all establishment registrations must be electronically submitted. It is essential to validate all registration data between October 1 and December 31 each year. In addition to registration, foreign manufacturers are also obligated to designate an US agent.
Manufacturers are required to complete the registration process with the FDA. The following types of businesses are mandated to provide a list of their devices:
Repackagers and relabelers
Reprocessors of single-use devices
Producers who remanufacture ancillary products and parts intended for direct consumer sale
U.S. producers of medical devices designated for export only
As part of the Medical Device Reporting program, any incidents where a device might have contributed to a fatality or caused a significant injury must be reported to the FDA. Moreover, various other issues also require reporting. Through the MDR regulation, both the FDA and manufacturers can monitor and pinpoint significant adverse events associated with medical devices. The primary goals of this regulation are to promptly identify and rectify issues.
In conclusion, understanding the regulatory landscape surrounding medical devices is crucial for manufacturers, importers, and distributors. The FDA plays a pivotal role in ensuring that these devices meet rigorous safety and efficacy standards, which ultimately safeguards the health and well-being of patients.
Navigating the intricacies of FDA regulations may seem daunting, but it's a vital step in bringing medical devices to market, ensuring they meet the highest standards of quality and safety. Whether you're dealing with Class I, Class II, or Class III devices, compliance with FDA requirements is a non-negotiable aspect of the process.
If you're in the medical device industry or planning to enter it, it's essential to stay informed about FDA regulations and any updates that may affect your business. Seeking professional guidance and consulting with experts in regulatory affairs can help streamline the compliance process and ensure your products reach the market smoothly.
Stay vigilant, stay informed, and prioritize patient safety in every step of the journey. Your commitment to compliance will not only benefit your business but also the countless individuals who rely on these life-saving devices. For any questions or assistance regarding FDA regulations or medical device compliance, don't hesitate to reach out to us. We're here to help you navigate the regulatory landscape and achieve success in the medical device industry.