Recent United States Food and Drug Administration Approval Process for Medical Devices

Overview Of The U.S. Fda Approval Process

The U.S. Food and Drug Administration (FDA) is a federal agency responsible for protecting public health by ensuring the safety, efficacy, and security of a wide range of products, including human and veterinary drugs, medical devices, vaccines, biologics, food, cosmetics, and tobacco products. Established in 1906, the FDA plays a crucial role in safeguarding public health and promoting innovation in the pharmaceutical and healthcare industries.

Historical Background

The origins of the FDA can be traced back to the late 19th and early 20th centuries, during a time of growing public concern over the lack of regulations in the food and drug industries. At that time, unsafe and ineffective products flooded the market, leading to numerous health hazards and fatalities. In response to public outcry, the Pure Food and Drug Act of 1906 was signed into law by President Theodore Roosevelt. This groundbreaking legislation aimed to prevent adulteration and misbranding of food and drugs, laying the foundation for future regulatory efforts.

Over the years, the FDA's scope expanded to encompass more product categories and address new challenges. Notable milestones include the creation of the Food, Drug, and Cosmetic Act in 1938, which required drug manufacturers to demonstrate their products' safety before marketing, and the establishment of the Center for Biologics Evaluation and Research (CBER) in 1902, responsible for regulating biological products.

Organizational Structure

The FDA operates within the Department of Health and Human Services (HHS) and is headed by the Commissioner of Food and Drugs. The Commissioner is appointed by the President and confirmed by the Senate. The FDA's organizational structure is divided into several key centers:

• Center for Drug Evaluation and Research (CDER): CDER is responsible for evaluating and approving new drugs for human use, overseeing generic drug approvals, and monitoring the safety of drugs on the market
• Center for Biologics Evaluation and Research (CBER): CBER regulates biological products, including vaccines, blood products, and gene therapies, ensuring their safety and effectiveness
• Center for Devices and Radiological Health (CDRH): CDRH evaluates and approves medical devices, such as pacemakers, X-ray machines, and diagnostic tests
• Center for Food Safety and Applied Nutrition (CFSAN): CFSAN ensures the safety and proper labeling of food, dietary supplements, and cosmetics
• Center for Tobacco Products (CTP): CTP regulates tobacco products to reduce tobacco-related diseases and deaths
• Office of Regulatory Affairs (ORA): ORA enforces FDA regulations and conducts inspections of facilities involved in the manufacture, distribution, and importation of FDA-regulated products. There are other offices involved in enabling the approval process of food and healthcare products

Functions And Responsibilities

• Product Review and Approval: One of the primary functions of the FDA is to review and approve products before they can be marketed and sold to the public. This process involves rigorous evaluation of scientific data, clinical trials, and manufacturing practices to ensure product safety and efficacy
• Post-Market Surveillance: After a product is approved, the FDA continues to monitor its safety and effectiveness through post-market surveillance programs. Adverse event reporting systems and other monitoring mechanisms help identify and address potential risks associated with products
• Regulation and Policy Development: The FDA develops and enforces regulations and policies that govern various aspects of product development, manufacturing, labeling, and marketing to protect consumers and promote public health
• Research and Innovation: The FDA conducts research and collaborates with the scientific community to stay abreast of the latest advancements and technologies, promoting innovation in medical product development and regulation
• Public Education: The FDA plays an essential role in educating the public about health and safety issues related to FDA-regulated products. This includes providing information about recalls, safety alerts, and proper product usage

Regulatory Processes

• New Drug Approval: Pharmaceutical companies seeking to market a new drug in the United States must submit extensive data from preclinical studies and human clinical trials to the FDA. The FDA reviews the data and decides whether the drug's benefits outweigh its risks, approving if the criteria are met
• Medical Device Clearance or Approval: Manufacturers of medical devices must go through either a premarket notification process (510(k) clearance) or a premarket approval (PMA) process, depending on the device's risk level. The FDA assesses the safety and effectiveness of the device before granting clearance or approval
• Food Safety and Labeling: The FDA establishes and enforces food safety standards, ensuring that food products are safe, properly labeled, and free from contamination or adulteration
• Biologics Approval: Biologics, which include vaccines, blood products, and gene therapies, undergo a comprehensive review process to ensure their safety, purity, and potency before approval

Key Pointers For Fda-Approved Medical Devices

Here are some key points to consider when analyzing FDA-approved medical devices:

• Device Classification: The FDA classifies medical devices into three main categories - Class I, Class II, and Class III - based on their potential risks to patients. Class I devices are considered low risk (bandages), Class II devices are moderate risk (infusion pumps), and Class III devices are high risk (implantable pacemakers)
• Pre-market Approval (PMA) vs. 510(k) Clearance: Depending on the device's classification, manufacturers may need to go through different regulatory pathways. Class III devices generally require a Pre-market Approval (PMA) application, which involves more rigorous testing and clinical data. Class II devices can often be cleared through a 510 (k) process, which demonstrates substantial equivalence to an existing, legally marketed device
• Clinical Trials and Data: For devices that require clinical data, the FDA evaluates the evidence provided by the manufacturer. Clinical trials are conducted to assess the device's safety and effectiveness in a relevant patient population. The quality and design of these trials, as well as the endpoints measured, play a crucial role in the FDA's approval decision
• Post-market Surveillance: After a device is approved and enters the market, the FDA continues to monitor its performance through post-market surveillance. This involves collecting and analyzing data on adverse events, product failures, and patient outcomes to ensure ongoing safety and effectiveness
• Innovation and Emerging Technologies: The medical device landscape is rapidly evolving with advancements in technology, including wearable devices, telemedicine tools, and AI-powered diagnostics. The FDA needs to strike a balance between encouraging innovation and ensuring patient safety
• Patient Access vs. Safety: There is often a delicate balance between providing patients with timely access to innovative medical devices and ensuring those devices are thoroughly tested for safety and efficacy. This balance can sometimes lead to debates about the appropriate level of regulatory oversight
• Global Harmonization: The FDA's approach to medical device regulation can influence or be influenced by global regulatory standards. Harmonization efforts seek to align regulatory requirements across different regions to streamline the approval process and enhance patient access to devices
• Review Panels: FDA has developed classifications for device types, a group of devices that do not have differing features regarding safety and effectiveness and require similar regulatory controls. The medical devices are grouped into medical specialties based on review panels as follows:

  • Anesthesiology
  • Cardiovascular
  • Dental
  • Ear, Nose, and Throat
  • Gastroenterology and Urology
  • General and Plastic Surgery
  • Hematology
  • Immunology
  • Microbiology
  • Neurology
  • Obstetrical and Gynecological
  • Ophthalmic
  • Orthopedic
  • Chemistry
  • Pathology
  • Physical Medicine
  • Radiology
  • Toxicology

Overview of Recently Approved Medical Devices

The FDA approved a total of 5,113 medical devices from 2019 to 2022. Of these, 2,348 were Class I devices, 2,432 were Class II devices, and 333 were Class III devices. The statistical analysis of the recently approved medical devices from 2019 to 2022 results in the following key findings:

U.S. FDA APPROVED Medical Devices from 2019 to 2022:

Source: US FDA, DBMR Analysis

The most common types of medical devices approved by the FDA in this period were:

• In vitro diagnostic (IVD) devices: 590 devices
• Implantable devices: 353 devices
• Diagnostic imaging devices: 273 devices
• Therapeutic devices: 208 devices
• General medical devices: 179 devices

The FDA also approved several innovative medical devices in this period, including:

• A new type of artificial pancreas that can automatically adjust insulin levels in people with diabetes
• A new type of pacemaker that can help to prevent sudden cardiac death
• A new type of cochlear implant that can provide better hearing for people with hearing loss
• A new type of cancer drug delivery system that can target tumors more precisely
• A new type of gene therapy that can treat a rare form of blindness

AI-enabled Medical Devices: The FDA's approval of these innovative medical devices is a sign of the progress that is being made in the field of medical technology. These devices have the potential to improve the lives of millions of people around the world. In addition to approving new medical devices, the FDA also updated the classification of several existing devices in this period. This includes a new classification for artificial intelligence (AI)-enabled medical devices. AI-enabled medical devices are software-based devices that use AI to perform tasks such as diagnosing diseases, monitoring patients, and providing treatment recommendations. The FDA's new classification for AI-enabled medical devices will help to ensure that these devices are safe and effective for patients.

The FDA's approval of new and innovative medical devices is a major step forward in the field of healthcare. These devices have the potential to improve the lives of millions of people around the world. The FDA's continued commitment to ensuring the safety and effectiveness of medical devices is essential to protecting public health.

Here are some additional observations about the trends in FDA medical device approvals from 2019 to 2022:

• The number of medical devices approved by the FDA has increased steadily over the past four years
• The proportion of Class I devices approved has decreased, while the proportion of Class II and Class III devices approved has increased
• The FDA has approved several innovative medical devices in recent years, including artificial pancreases, pacemakers, cochlear implants, and cancer drug delivery systems, among others

Regulatory Pathways for Medical Devices

The U.S. FDA provides various pathways for the approval of products including Premarket Notification 510(k), Premarket Approval (PMA), De Novo Pathway, Humanitarian Device Exemption (HDE), Custom Device Exemption (CDE), and Expanded Access Program (EAP).

Premarket Notification 510(k)

• Substantial Equivalence: The central concept of the 510(k) process is demonstrating substantial equivalence. The new device must be shown to have the same intended use as the predicate device and either the same technological characteristics or different characteristics that do not raise new questions of safety or effectiveness
• Predicate Device: A predicate device is an existing medical device that has been legally marketed in the U.S. before the new device. The new device's manufacturer compares their device to the predicate in terms of intended use, technological features, and other relevant factors
• Types of 510(k) Submissions:

  • Traditional 510 (k): This is the standard type of submission, where the manufacturer demonstrates substantial equivalence using appropriate testing, performance data, and other relevant information
  • Special 510 (k): This type of submission is used when design changes are made to an existing device that has an established performance standard or special controls. The special 510(k) focuses on demonstrating that the design changes do not affect the device's safety and effectiveness.

• FDA Review: The FDA reviews the 510 (k) submission to determine if the new device is indeed substantially equivalent to the predicate device. If the FDA agrees, the new device can be marketed in the U.S. If there are concerns or questions about the submission, the manufacturer may need to provide additional information or data
• Performance Data: While clinical trials are not always required for 510 (k) submissions, manufacturers might need to provide performance data, testing results, and other evidence that the device functions as intended and is safe for its intended use
• Guidance Documents: The FDA provides guidance documents that outline the specific requirements and recommendations for different types of devices and situations. Manufacturers should refer to these documents when preparing their 510 (k) submissions
• Review Time: The review time for a 510 (k) submission can vary depending on the complexity of the device, the completeness of the submission, and other factors. The FDA aims to complete the review within a specific timeframe, but this can vary in practice

Premarket Approval (PMA)

• Class III Devices: Class III devices are those that are deemed to have the highest risk to patients and may be used to support or sustain life, are implanted, or pose a substantial risk of illness or injury. Examples include implantable pacemakers, certain types of surgical implants, and life-sustaining devices
• Clinical Evidence: The PMA process requires manufacturers to provide comprehensive clinical evidence to demonstrate the safety and effectiveness of the device. This usually involves conducting well-designed clinical trials that assess the device's performance in a relevant patient population
• PMA Application: Manufacturers submit a PMA application to the FDA, which includes detailed information about the device's design, manufacturing process, proposed labeling, preclinical testing, and clinical trial data. The application is reviewed by FDA scientists, engineers, and medical experts
• Panel Review: In addition to FDA review, Class III devices usually undergo a review by an independent advisory panel, such as the Medical Devices Advisory Committee. The panel evaluates the clinical data, benefits, and risks of the device and makes recommendations to the FDA
• Safety and Effectiveness: The FDA's review focuses on ensuring the device's safety and effectiveness for its intended use. The device must demonstrate a favorable benefit-risk profile, meaning that its benefits outweigh its potential risks. Post-Approval Requirements: After approval, manufacturers are required to adhere to post-approval commitments, including ongoing monitoring of the device's performance, tracking adverse events, and reporting any new safety information to the FDA
• Humanitarian Device Exemption (HDE): For certain Class III devices that are intended to treat or diagnose rare diseases affecting fewer than 8,000 individuals in the U.S. annually, manufacturers can apply for a Humanitarian Device Exemption (HDE) instead of a full PMA. The HDE pathway has more lenient requirements and is designed to encourage the development of devices for rare conditions
• Review Time: The review time for a PMA application can vary, but it is typically longer than the review time for a 510(k) submission due to the complexity of clinical trial data and the higher risk associated with Class III devices

De Novo Pathway

• Novel Devices: The De Novo pathway is used for medical devices that are new and do not have a predicate device to which they can be compared for substantial equivalence under the 510 (k) pathway
• Risk-Based Classification: The De Novo pathway is generally suitable for Class I and Class II devices, which are lower-risk devices. The FDA assesses the level of risk and determines whether general controls, special controls, or a combination of both can provide reasonable assurance of safety and effectiveness
• Submission Process: Manufacturers submit a De Novo request to the FDA, which includes detailed information about the device's intended use, technological characteristics, clinical evidence, and risk assessment. The FDA reviews the submission to determine if the device meets the criteria for De Novo classification
• Device Review: The FDA assesses the submitted information to determine whether the device warrants a new classification and whether the controls in place are sufficient to ensure its safety and effectiveness. This process involves scientific, clinical, and regulatory assessments
• Risk Mitigation: The FDA may impose special controls on the device to mitigate identified risks. Special controls may include performance standards, post-market surveillance, patient registries, labeling requirements, and more
• Approval Decision: If the FDA determines that the device meets the criteria for De Novo classification and that the controls in place provide a reasonable assurance of safety and effectiveness, the device is classified as a Class I or Class II device. This allows similar devices to use the De Novo pathway in the future as predicates
• Subsequent 510(k) Submissions: Once a device is classified via the De Novo process, it can serve as a predicate device for future 510 (k) submissions. This means that other manufacturers can seek 510 (k) clearance by demonstrating substantial equivalence to the De Novo classified device
• Timeline and Review: The review time for a De Novo request can vary, but the FDA aims to complete the review within a specified timeframe. The timeline can be influenced by factors such as the complexity of the device and the information provided in the submission
• Some of the notable devices approved in 2022 through this pathway include:

U.S. FDA APPROVED Medical Devices through de novo, 2022:

Source: US FDA, DBMR Analysis

Humanitarian Device Exemption (HDE)

• Rare Diseases: The HDE pathway is intended for medical devices that are specifically designed to treat or diagnose diseases or conditions that are considered rare, meaning they affect a very small number of patients
• Patient Eligibility: To be eligible for an HDE, a device must be intended to benefit patients with a rare disease or condition, and there must be no comparable devices available for treatment or diagnosis
• Reasonable Assurance: Unlike traditional premarket approval (PMA) or 510(k) pathways, the HDE pathway does not require the same level of evidence of safety and effectiveness. Instead, the manufacturer must demonstrate that the device has the potential to provide a clinical benefit and that the probable benefits of the device outweigh the risks
• Clinical Data: Manufacturers seeking HDE approval usually need to provide clinical data, which can be less extensive than what is required for traditional approvals. The focus is on demonstrating that the device can provide meaningful benefits to patients despite the challenges of conducting extensive clinical trials in rare disease populations
• Review Process: The FDA reviews HDE submissions to ensure that the device meets the criteria for approval, including a favorable benefit-risk profile. The agency evaluates the clinical data, as well as the rarity and severity of the disease or condition
• Labeling: Devices approved under the HDE pathway are required to include labeling that informs users and patients about the device's status as an HDE and its intended use for the treatment or diagnosis of a rare disease
• Post-Approval Monitoring: After approval, manufacturers are expected to continue monitoring the device's performance, collecting safety and effectiveness data, and reporting any adverse events to the FDA
• Economic Considerations: Devices approved under the HDE pathway are not subject to the same user fee requirements as other device approvals, reflecting the unique challenges of developing products for rare diseases
• Access to Reimbursement: While HDE approval allows a device to be marketed, it's important to note that reimbursement for the device's use by healthcare payers can be a separate challenge. Manufacturers often need to work to secure reimbursement for devices approved under the HDE pathway
• Some of the notable applicants and their devices approved through this pathway in 2022 include

US FDA APPROVED Medical Devices through HDE, 2022:

Source: US FDA, DBMR Analysis

Custom Device Exemption (CDE)

The FDA recognizes that some medical devices may be custom-made or intended for a specific patient's unique anatomy or needs. These devices might not fit the typical regulatory framework since they are not mass-produced and are often made on a case-by-case basis. In such cases, the FDA may exercise enforcement discretion, meaning that they might not regulate these devices as stringently as mass-produced devices that follow the standard regulatory pathways. For a device to be considered under the custom device exemption, it generally needs to meet certain criteria:

• Patient-Specific: The device must be intended for use in a specific individual, considering their unique medical needs
• Sterility: The device should not be sterile or should be sterilized before use
• Not Commercially Available: The device must not be widely available in the market
• Manufactured by or on Order of a Physician or Dentist: Custom devices are often crafted or ordered by a healthcare professional based on a patient's specific medical needs
• Not Adulterated or Misbranded: The device must not be adulterated or misbranded, and it should not pose an unreasonable risk to the patient's health
• Non-Significant Change: Any changes to the device should not result in a significant change in design, components, method of manufacture, or intended use

It is important to note that the criteria for custom devices and the FDA's stance on enforcement discretion can change over time. The FDA periodically releases guidance documents that provide more detailed information on the regulatory approach for custom devices.

Expanded Access Program (EAP):

• Patient Eligibility: The program is designed for patients who have exhausted all available treatment options and have no comparable or satisfactory alternative therapies. Patients must have a serious or life-threatening disease or condition
• Investigational Products: The program provides access to investigational drugs, biologics, or medical devices that are still being evaluated in clinical trials and have not yet been approved by the FDA
• Physician Involvement: Access to investigational products is typically initiated by a licensed physician. The physician must determine that the potential benefits of the investigational product outweigh the potential risks for the individual patient
• FDA and Institutional Review Board (IRB) Oversight: While the FDA has regulatory authority over expanded access, the program requires submission to an Institutional Review Board (IRB) for ethical and safety review. The IRB ensures patient protection and reviews the proposed use of the investigational product
• Single Patient or Group Access: Expanded access can be granted on an individual patient basis or for groups of patients with similar medical conditions. Group access is sometimes referred to as "Intermediate-size Patient Population" access
• Application Process: The physician and, in some cases, the patient must apply to the FDA for expanded access. The application includes information about the patient's medical condition, the rationale for seeking access, and the investigational product being requested
• Manufacturer Consent: The manufacturer or sponsor of the investigational product must agree to provide access through the expanded access program. Manufacturers are not obligated to provide access and may have specific criteria for participation
• Costs and Logistics: Patients or their insurance providers are generally responsible for the costs associated with obtaining the investigational product, including its administration and monitoring. The logistics of obtaining and administering the product are managed by the healthcare provider

Safety Monitoring: Physicians and sponsors are required to report adverse events and outcomes to the FDA, ensuring that safety data is collected and evaluated