Adam Freeman, ex-FDA investigator for medical devices, describes the FDA regulatory pathways for medical devices, based on classification and intended use.
The regulatory pathway of a medical device depends mostly on its labeling. We can ask a philosophical question in an effort to tease out that pathway for which a device takes in becoming a medical device.
What separates an unregulated knife from an FDA regulated surgical scalpel? The indications for use. The indications you intend to market your product under will establish the framework of applicable regulations.
Table of Contents
Regulatory pathway for Class I Medical Devices
The surgical scalpel
Let’s explore how we progress through this thought experiment to arrive at the regulated surgical scalpel and its corresponding regulatory requirements. Then let’s explore those alternative pathways existing for other classes of devices and breakthrough technologies.
The knife evolves into the surgical scalpel by first establishing indications for use. An autoclavable blade for use in surgical procedures by a qualified professional, for example. The Federal Food, Drug, and Cosmetic Actdefines a regulated device in part in section 201(h). That section reads in part,
“The term ‘‘device’’ *** means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is ***intended for use in the diagnosis of disease or other conditions, or in thecure, mitigation, treatment, or prevention of disease, in man or other animals, or ***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 is not dependent upon being metabolized for the achievement of its primary intended purposes”.
Once we have identified the intent for which our device is intended to be used, we can perform a search to determine the classification of the device. When there is no defined classification for the device, we will explore those pathways too. Contained within Title 21 of the United States Code of Federal Regulations is part 860. This part defines the Medical Device Classification Procedures. These classification procedures are prescribed by FDA for device developers to follow to define the risks class in which their product is categorized under.
FDA Regulatory Pathways for Medical Devices: Risk Classes
Classes are broken into three risk classes based on FDA’s own risk benefit analysis. These classes are defined as follows:
“Class I means the class of devices that are subject to only the general controls authorized by or under sections 501 (adulteration), 502 (misbranding), 510 (registration), 516 (banned devices), 518 (notification and other remedies), 519 (records and reports), and 520 (general provisions) of the act. A device is in class I if (i) general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device, or (ii) there is insufficient information from which to determine that general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device or to establish special controls to provide such assurance, but the device is not life-supporting or life-sustaining or for a use which is of substantial importance in preventing impairment of human health, and which does not present a potential unreasonable risk of illness of injury. ***
Class II means the class of devices that is or eventually will be subject to special controls. A device is in class II if general controls alone are insufficient to provide reasonable assurance of its safety and effectiveness and there is sufficient information to establish special controls, including the promulgation of performance standards, post-market surveillance, patient registries, development and disseminationof guidance documents (including guidance on the submission of clinical data in premarket notification submissions in accordance with section 510(k) of the act), recommendations, and other appropriate actions as the Commissioner deems necessary to provide such assurance. For a device that is purported or represented to be for use in supporting or sustaining human life, the Commissioner shall examine and identify the special controls, if any, that are necessary to provide adequate assurance of safety and effectiveness and describe how such controls provide such assurance. ***
Class III means the class of devices for which premarket approval is or will be required in accordance with section 515 of the act. A device is in class III if insufficient information exists to determine that general controls are sufficient to provide reasonable assurance of its safety and effectiveness or that application of special controls described in paragraph (c)(2) of this section would provide such assurance and if, in addition, the device is life-supporting or life-sustaining, or for a use which is of substantial importance in preventing impairment of human health, or if the device presents a potential unreasonable risk of illness or injury.”
Has the classification already been defined?
By searching within part 862 to 892 of Title 21 of the United States Code of Federal Regulations, one can determine if a classification has been already defined for their product.
21 CFR section 860.1(b) reads in part,
“This part prescribes the criteria and procedures to be used by classification panels in making their recommendations and by the Commissioner in making the Commissioner’s determinations regarding the class of regulatory control (class I, class II, or class III) appropriate for particular devices. Supplementing the general Food and Drug Administration procedures governing advisory committees (part 14 of this chapter), this part also provides procedures for manufacturers, importers, and other interested persons to participate in proceedings to classify and reclassify devices. This part also describes the kind of data required for determination of the safety and effectiveness of a device, and the circumstances under which information submitted to classification panels or to the Commissioner in connection with classification and reclassification proceedings will be available to the public”.
Classifications for devices are defined within 21 CFR in the following parts:
- Part 862 – Clinical Chemistry and Clinical Toxicology Devices
- Part 864 – Hematology and Pathology Devices
- Part 866 – Immunology and Microbiology Devices
- Part 868 – Anesthesiology Devices
- Part 870 – Cardiovascular Devices
- Part 872 – Dental Devices
- Part 874 – Ear, Nose, and Throat Devices
- Part 876 – Gastroenterology – Urology Devices
- Part 878 – General and Plastic Surgery Devices
- Part 880 – General Hospital and Personal Use Devices
- Part 882 – Neurological Devices
- Part 884 – Obstetrical and Gynecological Devices
- Part 886 – Ophthalmic Devices
- Part 888 – Orthopedic Devices
- Part 890 – Physical Medicine Devices
- Part 892 – Radiology Devices
Narrowing down the specific device classification
For the intentions of defining our surgical scalpel, we will turn our attention to Part 878 – General and Plastic Surgery Devices. Within this part, we find under section 878.4800 the appropriate classification for our surgical scalpel. This section reads in part,
“Manual surgical instrument for general use.
(a) Identification. A manual surgical instrumentfor general use is a non-powered, hand-held, or hand-manipulated device, either reusable or disposable, intended to be used in various general surgical procedures. The device includes the applicator, clip applier, biopsy brush, manual dermabrasion brush, scrub brush, cannula, ligature carrier, chisel, clamp, contractor, curette, cutter, dissector, elevator, skin graft expander, file, forceps, gouge, instrument guide, needle guide, hammer, hemostat, amputation hook, ligature passing and knot-tying instrument, knife, blood lancet, mallet, disposable or reusable aspiration and injection needle, disposable or reusable suturing needle, osteotome, pliers, rasp, retainer, retractor, saw, scalpel blade, scalpel handle, one-piece scalpel, snare, spatula, stapler, disposable or reusable stripper, stylet, suturing apparatus for the stomach and intestine, measuring tape, and calipers. A surgical instrument that has specialized uses in a specific medical specialty is classified in separate regulations in parts 868 through 892.
(b) Classification. Class I (general controls).
The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter, subject to the limitations in §878.9.” 
Within this definition for a manual surgical instrument for general use, we find our surgical scalpel is classified as a Class I medical device.
This translates to this device requiring establishment of those general control requirements prescribed by FDA. Those general control requirements are defined within the United States Federal Food Drug and Cosmetic Act, and are listed as follows:
- Section 501 (adulteration)
- Section 502 (misbranding)
- Section 510 (registration)
- Section 516 (banned devices)
- Section 518 (notification and other remedies)
- Section 519 (records and reports)
- Section 520 (general provisions)
Regulatory Pathway for Class II Medical Devices
Let’s consider other devices and their prescribed requirements by classification. If we bump up our risk category by adding power to our cutting device, we arrive at a Class II medical device. 21 CFR Section 878.4400 reads in part,
“Electrosurgical cutting and coagulation device and accessories.
(a) Identification. An electrosurgical cutting and coagulation device and accessories is a device intended to remove tissue and control bleeding by use of high-frequency electrical current.
(b) Classification. Class II”.
Now, since we have bumped up our risk class to a Class II regulated medical device, our product requires clearance from FDA through their pre-market submission process. That process is required before the product is cleared for marketing and sale in the United States. Also, as a Class II device, our requirements evolve from general controls to those controls prescribed by current Good Manufacturing Practice requirements for manufacturing medical devices.
These requirements translate to establishment of a Quality Management System which steers and manages the design, manufacturing processes, and overall quality and compliance to those requirements prescribed by FDA and harmonized standards. I have found a useful listing of those requirements buried in one of FDA’s compliance guidance program manuals. FDA’s CPGM 7382.845, Inspection of Medical Device Manufacturers , list those requirements as they are defined within Title 21 of the United States Code of Federal Regulations . Those requirements are as follows:
- Part 7, Subpart C, Recalls
- Part 11, Electronic Records and Electronic Signatures
- Parts 16 and 17, Hearing Procedures
- Part 800, Subpart C, Administrative Detention
- Part 803, Medical Device Reporting
- Part 806, Reports of Corrections and Removals
- Part 807, Establishment Registration and Device Listing
- Part 809.10, Labeling For In Vitro Diagnostic Devices
- Part 810, Medical Device Recall Authority
- Part 820, Current Good Manufacturing Practices/Quality System Regulation
- Part 821, Tracking Requirements
- Parts 1000–1050, Radiation Regulations and Standards
Every Class II or Class III product shall meet these listed requirements which are pertinent to their device (Tracking Requirements and Radiation Regulations are device specific).
Continuing down our path of the development of a Class II product, we revisit the pre-market submission process.
FDA 510(K) submission: Pre-market submission
This process can be summarized in part by this quote borrowed from FDA’s website.
“A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is as safe and effective, that is, substantially equivalent, to a legally marketed device *** Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalence claims.”
As FDA promotes transparency in their processes, they have published many useful guidances for the submission process of 510(k)s. I recommend their guidance titled in part, “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] Guidance for Industry and Food and Drug Administration Staff”. This document identifies what information is requested for submitting a premarket submission to FDA. Hiring a 510(k) submissions expert can help you ensure the document is prepared as per the guidelines.
When there is uncertainty whether a device can be perceived as substantially equivalent or a new device,a new device translating to the technology is novel or an existing device which is desired to be used for a new indication for use, FDA offers a mechanism for those exploring locking down their device classification and risk class. This is a best practice, in my opinion, before proceeding down the development pathway. The mechanism is called the Q-Submission process.
In FDA’s guidance titled in part, “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program Guidance for Industry and Food and Drug Administration Staff”, FDA writes in part:
“this guidance is to provide an overview of the mechanisms available to submitters through which they can request feedback from or a meeting with the Food and Drug Administration (FDA) regarding potential or planned medical device Investigational Device Exemption (IDE) applications, Premarket Approval (PMA) applications, Humanitarian Device Exemption (HDE) applications, Evaluation of Automatic Class III Designations (De Novo requests), Premarket Notification (510(k)) Submissions, Clinical Laboratory Improvement Amendments (CLIA) Waiver by Applications (CW), Dual 510(k) and CLIA Waiver by Application Submissions (Duals), Accessory Classification Requests, and certain Investigational New Drug Applications (INDs) and Biologics License Applications (BLAs) submitted to the Center for Biologics Evaluation and Research (CBER)) (specifically, INDs and BLAs for devices that are regulated as biological products”.
Whether your organization intends to bring a new device, Class II device, or Class III device to market, FDA is open to assisting you with this process if your organization is determined enough and patient enough to follow FDA’s prescribed pathways. Those “pre-“ submission meetings can be invaluable in defining those baseline decisions regarding the device classification, regulatory framework, and pathway the developer shall follow based on that classification.
Since we have discussed those pathways now for Class I and Class II products, let’s dive deeper into those other pathways for device approval.
Regulatory pathway for Class III medical devices
Class III medical devices are grouped in this category because they are the perceived to be in the highest risk class for medical devices. FDA writes in part on their website,
“Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of Class III devices. Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing approval.” 
As with many FDA processes, FDA has published a plethora of guidances to support the pathway for clearing Class III medical devices.
The two foundational documents I recommend for following the development pathway for a Class III device are:
- Acceptance and Filing Reviews for “You remind me of everything that followed. Every day since then has been a gift.” Guidance for Industry and Food and Drug Administration Staff.
- Guidance for Industry and FDA Staff Premarket Approval Application Modular Review. 
Much like a pre-market submission, a pre-market approval application requires modules of data be submitted to FDA for review and approval before those products are cleared for use. FDA appreciates being engaged with the developer during the development pathway so they can evaluate testing protocols before and after they are implemented. Frequently, with high risk devices, development activities for those devices already require engagement with FDA in order to deploy design validation testing (testing in humans). The mechanism for performing this testing is through the Investigational Device Exemption (IDE) process.
Class III Medical Device Regulatory Pathway: Example
For an example of a device being developed down the Class III pathway, including the IDE study, let’s consider a cardiovascular device. These are frequently Class III because they are usually life sustaining or high risks devices. For this example, lets consider a ventricular assists / bypass device. A ventricular bypass (assist) device is defined in section 21 CFR 870.3545. That definition reads in part,
“A ventricular bypass (assist) device is a device that assists the left or right ventricle in maintaining circulatory blood flow. The device is either totally or partially implanted in the body. ***
Classification. Class III (premarket approval).” 
Investigational Device Exemption (IDE) pathway
The Investigational Device Exemption (IDE) pathway is for high risks products requiring permission for use in controlled studies to collect clinical data for design validation. FDA has provided this pathway to enable prototypes be used for evaluation to demonstrate safety and efficacy. Special requirements have been defined for proceeding down the IDE pathway. Those requirements are listed below:
- 21 CFR 812, Investigational Device Exemptions
- 21 CFR 50, Protection of Human Subjects
- 21 CFR 56, Institutional Review Boards
- 21 CFR 54, Financial Disclosure by Clinical Investigators
- 21 CFR 820 Subpart C, Design Controls of the Quality System Regulation
The design validation, IE clinical trial, of this ventricular bypass (assist) device is a candidate to use this IDE development pathway as a milestones toward obtaining pre-market approval as a Class III FDA cleared medical device.
If a developer believes that their device is unclassified, is a novel technology, or a novel indication for use, the pathway for development may be through one of FDA’s alternative pathways. Those alternatives include the Humanitarian Device Exemption (HDE) exemption pathway, the De Novo requests pathway, and FDA’s breakthrough and emergency pathways.Let’s break these pathways apart individually and dissect how they work based on their intent.
A footnote in FDA’s guidance, Medical Device Classification Product Codes Guidance for Industry and Food and Drug Administration Staff,reports in part,
“An unclassified device is a pre-amendments device for which a classification regulation has not been promulgated. Unclassified devices require submission of a 510(k)premarket notification to CDRH. A not-classified device is a post-amendments device for which the Agency has not yet reviewed a marketing application or for which theAgency has not made a final decision on such a marketing application”.
Although FDA recommends an unclassified device to be submitted through their 510(k) process, I recommend the developer follow the Q-Submission pathway first to get concurrence from FDA regarding the risk class for their device. An alternative to this pathway is a De Novo request. A De Novo request is explained in part on FDA’s website as follows,
“a pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legallymarketed predicate device. De Novo classification is a risk-based classification process.
Devices that are classified into class I or class II through a De Novo classification request (De Novo request) may be marketed and used as predicates for future premarket notification [510(k)] submissions.”
A De Novo request is similar to a Q-Submission in that both are seeking concurrence from FDA regarding the risk classification of the product. That risk classification is essential to define, in order to proceed with the design and development pathway in implementing those pertinent requirements, controls, and studies. A new device indicated for the treatment of Covid-19 could be considered for development through the De Novo request pathway as the technology is still considered novel. However, as those kinds of technologies are not only novel, they are needed under an emergency situation making other pathways opportunities for expedited deployment.
Breakthrough Devices Program
Covid-19 and Medical Device Innovation
With the challenges encountered due to Covid-19, breakthrough pathways and Emergency Use Authorization pathways have become hot topics for emerging technologies intended to help fight the outbreak. Although these pathways have existed for a long time, their popularity as a pathway for bringing new technologies to market has been noticeably increasing with the crisis.
Let’s break down each of those pathways individually to understand better how they work.
FDA reports on their website,
“The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and De Novo marketing authorization, consistent with the Agency’s mission to protect and promote public health”.
In order for a product to be eligible for the Breakthrough Devices Program the device must demonstrate greater effectiveness over current treatment or diagnosis technologies available in treatment of life-threatening or irreversibly debilitating human diseases or conditions. Additionally, that product must meet at least one of the following requirements:
- Represents Breakthrough Technology
“FDA considers whether the device represents a novel technology or novel application of an existing technology that has the potential to lead to a clinical improvement in the diagnosis, treatment (including monitoring of treatment), cure, mitigation, or prevention of the life-threatening or irreversibly debilitating disease or condition”. 
- No Approved or Cleared Alternatives Exist
“FDA considers whether there is a drug, biological product, device, or combination product that has received FDA marketing authorization after premarket review for the same indication(s) being considered (i.e., whether there is an alternative product that FDA has approved, cleared, or licensed, or for which FDA has granted a De Novo request)”.
- Offers Significant Advantages over Existing Approved or Cleared Alternatives,
“FDA considers the potential, compared to existing approved or cleared alternatives, “to reduce or eliminate the need for hospitalization, improve patient quality of life, facilitate patients’ ability to manage their own care (such as through self-directed personal assistance), or establish long-term clinical efficiencies.””
- Device Availability is in the Best Interest of Patients
“FDA considers whether the proposed device and indications for use provide another type of specific public health benefit”.
In addition to this guidance referenced above, FDA has published a variety of development guidances and tools intended to assists companies with providing FDA with the data they need in an expedited manner. This is also the case for technologies pushed through Emergency Use Authorizations.
Emergency Use Authorizations
Emergency Use Authorizations (EAUs)may be initiated by FDA if they determine there is an emergency need which is unfulfilled. In order to obtain an EUA for your product, FDA expects your organization to set up a pre-EUA meeting. Templates exists on FDA’s website for the information they are seeking to initiate the EUA pathway. Once the Pre-EUA meeting has kicked off, FDA will provide guidance on how they want to collaborate with your organization to proceed with development and release of your product.
Humanitarian Device Exemption
Humanitarian Device Exemption and Humanitarian Use Devices are pathways for consideration for devices which are intended to be used on a small patient population. FDA defines a Humanitarian Use Device (HUD) in part as
“a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year”. 
HDEs allow exemption from the requirements to demonstrate effectiveness of the device in accordance those requirements prescribed within sections 514 and 515 of the Food Drug and Cosmetic Act.Sticking with our cardiovascular examples, HDEs have been issued by FDA for pediatric ventricular assist devices because those patient populations meet FDA’s criteria to constitute that condition being eligible under their HDE pathway (IE. that disease or condition affects or is manifested in not more than 8,000 individuals in the United States per year).
Although FDA has the intention of being transparent within those processes they offer to the public, those processes at times can be cryptic and daunting. I was an Investigator for the Food and Drug Administration seven and a half years before taking the leap into consulting. During my time as a regulatory consultant I’ve assisted with these FDA regulatory pathways for medical devices. The leap from regulating to coaching on design, manufacturing, and compliance has been refreshing. Its also enabled me the opportunity to take on innovative and entrepreneurial projects which is something I am passionate about.
Need help to figure out the best FDA pathway for your medical device? Consult Adam Freeman for regulatory support.
OR View other FDA submission experts on Kolabtree.
- Federal Food, Drug, and Cosmetic Act: https://www.govinfo.gov/content/pkg/USCODE-2014-title21/pdf/USCODE-2014-title21.pdf
- Title 21 of the United States Code of Federal Regulations: https://www.govinfo.gov/content/pkg/CFR-2011-title21-vol8/pdf/CFR-2011-title21-vol8-chapI-subchapH.pdf
- FDA’s CPGM 7382.845, Inspection of Medical Device Manufacturers: https://www.fda.gov/media/80195/download
- FDA’s Premarket Notification Website: https://www.fda.gov/medical-devices/premarket-submissions/premarket-notification-510k
- The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] Guidance for Industry and Food and Drug Administration Staff: https://www.fda.gov/media/82395/download
- Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program Guidance for Industry and Food and Drug Administration Staff: https://www.fda.gov/media/114034/download
- FDA’s Premarket Approval (PMA) Website: https://www.fda.gov/medical-devices/premarket-submissions/premarket-approval-pma
- Acceptance and Filing Reviews for Premarket Approval Applications (PMAs) Guidance for Industry and Food and Drug Administration Staff: https://www.fda.gov/media/83408/download
- Guidance for Industry and FDA Staff Premarket Approval Application Modular Review: https://www.fda.gov/media/73513/download
- Medical Device Classification Product Codes Guidance for Industry and Food and Drug Administration Staff: https://www.fda.gov/media/82781/download
- FDA’s De Novo Classification Request Website: https://www.fda.gov/medical-devices/premarket-submissions/de-novo-classification-request
- FDA’s Breakthrough Devices Program: https://www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program
- FDA’s Guidance Breakthrough Devices Program Guidance for Industry and Food and Drug Administration Staff: https://www.fda.gov/media/108135/download
- FDA’s Humanitarian Use Device (HUD) Designation Program:https://www.fda.gov/industry/developing-products-rare-diseases-conditions/humanitarian-use-device-hud-designation-program