Table 1 Overview of the risk classes for medical devices. FDA, Food and Drug Administration; PMA, Premarket Approval
Sources: Makower Report: FDA Impact on U.S.: Medical Technology Innovation. Available at: https://www.advamed.org/sites/default/files/resource/30_10_11_10_2010_study_cagenda_makowerreportfinal.pdf. Accessed June 8, 2020; Food and Drug Administration: Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval:Guidance for Industry and Food and Drug Administration Staff. Available at: https://www.fda.gov/media/88381/download. Accessed June 8, 2020.

AAOS Now

Published 7/1/2020
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Martha Murray, MD, MS, FAAOS; Jonathan Dubin, MD, FAAOS

An Overview of the FDA Approval Process for Devices

In 1976, Congress passed the Medical Device Amendments Act, which granted the Food and Drug Administration (FDA) authority to regulate medical devices. Within the FDA, the Center for Devices and Radiological Health (CDRH) typically oversees the process; however, if a device includes a biologic component, the Center for Biologics Evaluation and Research may oversee its evaluation. At present, the CDRH regulates nearly all orthopaedic devices.

Although what constitutes a device may seem intuitive, the FDA strictly adheres to the definition in 201(h) of the Federal Food, Drug, and Cosmetic Act (see sidebar). This has led to some devices not commonly thought of as “devices” to be regulated as such (e.g., hyaluronic acid, certain demineralized bone matrices). In addition, some devices are considered combination products, meaning that a device is combined with a biologic, drug, or both. There are currently 62 orthopaedic combined products on the market, including polymethylmethacrylate mixed with antibiotics and bone morphogenetic protein-2 combined with instrumentation.

The FDA created a risk-based, tiered system to facilitate regulation of medical devices (Table 1). Class I devices typically undergo little premarket oversight and must simply adhere to Current Good Manufacturing Practices (Fig. 1, available in the online version). A class II device usually requires premarket notification of the FDA by the manufacturer in a process also often called “510(k),” per the section of law delineating its conduct. Most orthopaedic implants gain approval through the 501(k) process by demonstrating that they are “substantially equivalent” to existing legally marketed devices. In most instances, proof of substantial equivalence does not require manufacturers to conduct clinical trials, which are a hallmark of the approval process for both new drugs and class III devices. As a result, most medical devices reach the market without demonstrating clinical safety or effectiveness.

Fig. 1 The Food and Drug Administration regulatory pathways for medical devices. The recommended pathway for devices is largely based on risk to the patient. Higher-risk devices have a higher burden of evidence of safety and effectiveness prior to approval. PMA, premarket approval
Sources: Food and Drug Administration: Homepage. Available at: https://www.fda.gov. Accessed June 8, 2020; Maak TG, Wylie JD: Medical dvice regulation: a comparison of the United States and the European Union. J Am Acad Orthop Surg 2016;24:537‐43; Kirkpatrick JS, Stevens T: The FDA process for the evaluation and approval of orthopaedic devices. J Am Acad Orthop Surg 2008;16:260-7.

Although most orthopaedic devices are regulated by the 510(k) pathway based on predicate devices, some devices have no suitable predicates. For a lower-risk device without a predicate device, a manufacturer may elect to pursue a 510(k) de novo submission. Rather than providing evidence of equivalence to a predicate device, the manufacturer proposes a new list of special controls that provide reasonable assurance of safety and effectiveness for the labeled use of the product. The data can include additional preclinical or clinical studies, as well as biocompatibility or compositional testing. In total, 262 devices have entered the market via this method, the most publicized of which are the ECG App for the Apple Watch and 3M N95 respirator designed for home use (not the one designed for healthcare facilities).

Currently, two orthopaedic devices are cleared via the de novo pathway. Once a device is cleared, the special controls become requirements for other devices wishing to receive 510(k) clearance using the de novo device as a predicate.

The premarket approval (PMA) process is the most rigorous level of scientific and regulatory review by the FDA, and the vast majority of class III devices are approved via this pathway. As class III devices carry the highest amount of risk, they warrant the highest level of review for both safety and efficacy. In addition to the general and special controls required for 510(k) applications, PMA also requires information on sterility, biocompatibility, toxicology, and shelf life, as well as any other laboratory or animal tests, clinical trial data, and a complete description of the manufacturing process, which are not typically required for 510(k) applications for class I or II devices. Numerous FDA guidance documents describe the data required for PMA, which may also be clarified for an individual product during a pre-submission meeting.

It is important for surgeons to understand the different levels of scrutiny given to particular devices before the products enter the consumer market. Most devices are not “approved” by the FDA, as often advertised, but rather “cleared.” This is an important distinction the FDA carefully applies depending on the extent of premarket assessment. This process puts the burden of evaluating the clinical effectiveness of “cleared” devices even more so on the orthopaedic surgeon.

It is important to note that relatively few orthopaedic devices go through the PMA process before reaching the market, as more than 95 percent are approved through the 510(k) process based on predicate devices. In some cases, the predicate device used for clearance may have even been withdrawn from the market, and in other cases split predicate devices are used (one for intended use and one for technological characteristics).

In addition, many devices approved via the PMA process pathway undergo substantial postmarket device modification after reaching the market, often without any supporting clinical data. The modifications can include actual structural changes to the device, but also changes in labeling, expanded indications, changes in manufacturing or packaging, etc. Devices cleared through 510(k) can undergo modifications as well, but major changes typically require new 510(k) submission.

The FDA can also require postmarket data collection from manufacturers for certain class III devices. In 1997, Congress passed legislation requiring the FDA to utilize the “least burdensome” amount of data that would allow safe evaluation of a device prior to marketing. This has led the FDA to approve PMA devices more quickly and with less premarket data under the stipulation that the manufacturer perform postmarket studies to ensure real-world safety and effectiveness. As stipulated under section 522 of the Federal Food, Drug, and Cosmetic Act, the FDA can also require postmarket surveillance of certain class III devices.

Fortunately, the FDA has made public its evaluation process of each device, which can be found by searching for a particular device on its databases at www.fda.gov.

In particular, summaries of safety and effectiveness data for devices that have gone through the PMA process offer thorough reports of clinical and nonclinical data to support approval, as well as device descriptions and labeled indications. Other important guidance documents can be found pertaining to recommendations of how to navigate the various pathways with a new device. When considering the use of a new medical device or product, surgeons should consider whether the available risk/benefit information is sufficient to justify the use of that product for a particular patient.

Martha Murray, MD, MS, FAAOS, is a professor of orthopaedics at Harvard Medical School and Boston Children’s Hospital and is a member of the AAOS Committee on Devices, Biologics, and Technology (DBT). She can be reached at martha.murray@childrens.harvard.edu.

Jonathan Dubin, MD, FAAOS, is an associate professor of orthopaedics at the University of Missouri–Kansas City Medical School and serves as chief of orthopaedic trauma at Truman Medical Center. He is a member of the AAOS Committee on DBT. He can be reached at dubinj@umsystem.edu.

FDA definition of a medical device

Per section 201(h) of the Food, Drug, and Cosmetic Act, a device is: An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part or accessory which is:

  •  recognized in the official national formulary, the United States Pharmacopoeia, or any supplement to them
  • intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, in man or other animals
  •  intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent
    upon being metabolized for the achievement of its primary intended purposes. The term “device” does not include software functions excluded pursuant to section 520(o).

FDA, Food and Drug Administration
Source: Food and Drug Administration: How to Determine If Your Product Is A Medical Device. Available at: https://www.fda.gov/medical-devices/classify-your-medical-device/how-determine-if-your-product-medical-device. Accessed May 21, 2020