As a professional involved in an FDA

Requirements of Laws and Regulations Enforced
by the U.S. FDA for Medical Devices

By Dan Zrymiak

As a professional involved in an FDA-regulated company, I receive requests on FDA compliance. I have prepared the following summary of the common FDA laws affecting the manufacture and sale of Medical Devices into the United States.

This summary is adapted from FDA guidance publications, and is intended to provide a brief description on the following elements which are common to FDA Medical Device Regulation:

* Classification of Devices
* Reclassification
* Premarket Notification for New Devices
* Requirements for all Devices
* Adulteration
* Misbranding
* Device Registration and Listing
* Good Manufacturing Practice Regulations
* Inspection, Administrative Detention, Records and Reports
* Notification; Repair, Replacement or Refund; Mandatory Recall and Tracking
* Banned Devices
* Investigational Devices
* Custom Devices
* Imported Devices

The Medical Device Amendments of 1976 revised and extended the device requirements of the 1938 Federal Food, Drug, and Cosmetic Act. The Federal Food, Drug, and Cosmetic Act was subsequently amended by the Safe Medical Devices Act of 1990 (SMDA) and the Medical Device Amendments of 1992. Under the Federal Food, Drug, and Cosmetic Act, a device is defined as any health-care product that does not achieve its principle intended purposes by chemical action in or on the body or by being metabolized. The term "devices" also includes components, parts, or accessories of devices, and diagnostic aids.

Classification of Devices

The Federal Food, Drug, and Cosmetic Act (Sec. 513) requires that all devices, for human use, marketed in the United States prior to the passage of the 1976 Amendments be classified by FDA, based on recommendations of expert panels, into one of three regulatory classes.

Class I- General Controls: Class I products are subject only to the general controls which apply to all devices, irrespective of class. General controls include the registration of manufacturers, recordkeeping requirements, labeling requirements, and compliance with Good Manufacturing Practice Regulations.

Class II- Special Controls: Devices for which general controls are not sufficient to ensure safety and effectiveness, and for which enough information exists to develop special controls to provide such assurance, including performance standards, postmarket surveillance, patient registries, guidelines, recommendations and other appropriate actions.

Class III- Premarket Approval: Implanted and life-supporting or life-sustaining devices are required to have FDA approval for safety and effectiveness before they can be marketed unless FDA determines that premarket approval is not necessary. Premarket approval can be required of other devices if general controls are not sufficient to ensure safety and effectiveness and there is not enough information to establish special controls.

Reclassification

Any interested person may petition the Agency to reclassify a device either to lower the classification from III to II or from II to I, or in some instances to raise the classification. FDA may also begin a reclassification action on its own initiative.

Premarket Notification for New Devices

Unless specifically exempted by regulation, all manufacturers are required to give FDA 90 days notice before they intend to introduce a device on the market by submitting a premarket notification (Sec. 510(k)). During the 90-day period, FDA will determine whether the device is or is not equivalent to a pre-amendment device. A device may not be marketed until the firm receives a notice from the Agency that their device is substantially equivalent to a device that does not require preamendment approval.

Those firms submitting premarket notifications (510(k)) claiming substantial equivalence to preamendment Class III devices must certify that they have conducted a reasonable search of all known information about the predicate device, and provide to FDA a summary of all adverse safety and efficacy data, and make such information available to FDA upon request. Those firms submitting premarket notifications to FDA for Class I and II devices must provide an adequate summary of safety and efficacy data which is available to FDA upon request, and made available to the public within 30 days of any request once the device has been found to be substantially equivalent.

Unless and until FDA determines that the device is substantially equivalent to a device that does not require premarket approval the device is Class III. The manufacturer will then have to provide FDA with a premarket approval (PMA) application containing evidence which substantiates that the device is safe and effective before the device may be commercially distributed to the public. The manufacturer may, however, try to convince FDA to reclassify the device by filing a reclassification petition.

A manufacturer must submit a premarket notification when introducing:

- A new device to the market.
- A device new to a particular manufacturer even though a similar device may already be marketed by another manufacturer.
- A device which is a modification of an existing product if the modification has a significant impact on the safety and effectiveness of the device.
- An old device with a major change in intended use.

A premarket notification to FDA must include the following information:

- The trade and common name of the device.
- Labeling and advertisements describing the device, its intended use, and directions for use.
- The classification of the device.
- A statement of how the device is either similar to or different from others on the market, with data to support the statement.

The regulation for premarket notification is found in 21 CFR Part 807, Subpart E.

Requirements for All Devices

The Food and Drug Administration may initiate an enforcement action (seizure, injunction, prosecution, and/or civil penalties) to protect the public from adulterated or misbranded devices.

All medical devices are subject to the following general control requirements:

Adulteration

A device is considered adulterated (Sec. 501):

(1) if it consists in whole or in part of any unsanitary substance,

(2) if it has been manufactured, packed or held under unsanitary conditions;

(3) if its container is composed of a poisonous substance;

(4) if it contains an unsafe color additive;

(5) if its quality or purity falls below that which it purports to possess;

(6) if it does not comply with an applicable performance standard;

(7) if it does not comply with an applicable premarket approval requirement;

(8) if it is a banned device;

(9) if it is not manufactured in accordance with Good Manufacturing Practice Regulations; or

(10) in the case of an investigational device, if it fails to comply with applicable requirements under the investigational device regulations.

Misbranding

A device is considered misbranded (Sec. 502):

(1) if its labeling is false or misleading;

(2) if the label does not contain: the name and address of the manufacturer, packer, or distributor, and an accurate statement of the quantity of contents;

(3) if the required information is not prominently and legibly placed on the label in English;

(4) if the established name of the device does not appear in type at least half as large as the proprietary name used;

(5) if its labeling does not bear adequate directions for use and adequate warnings against unsafe use;

(6) if it is dangerous to health;

(7) if it is a restricted device and its advertisements are false or misleading or do not meet minimum requirements for disclosure of product information;

(8) if it is a restricted device and it is not sold, distributed, or used in compliance with regulations;

(9) if it does not comply with an applicable performance standard labeling requirement;

(10) if it was made in an establishment not registered under Section 510, or not listed under Section 510(j), or if a notice respecting a device was not provided as required by Section 510(k); or

(11) if there was a failure to comply with requirements for notification, records, and reports.

Device Registration and Listing

Foreign manufacturers of devices are not required to register, but are encouraged to do so. However, they are required to list their devices with FDA.

Good Manufacturing Practice Regulations

Manufacturers of finished devices are required to comply with regulations prescribing Current Good Manufacturing Practice for devices (21 CFR 820), to prevent production of defective products.

Inspection, Administrative Detention, Records and Reports

FDA investigators are authorized to enter and inspect any factory, warehouse or establishment where devices are manufactured, processed, packed, or held. Manufacturers of restricted devices must permit FDA investigators to inspect all things in the facility, including records, files, papers, processes, controls and facilities with the exception of certain financial, sales, personnel, or research data (Secs. 704 and 304(g)). Manufacturers of all devices must permit investigators to inspect and provide copies of records required to be kept by the Good Manufacturing Practice Regulations.

In accordance with the Medical Device Reporting (MDR) requirements manufacturers shall notify the FDA's Center for Devices and Radiological Health as soon as possible but no later than five calendar days after receipt of information, concerning any device that has been responsible for, or is associated with, a death or serious injury. A device malfunction that would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, shall be reported by the manufacturer to FDA within 15 working days (21 CFR 803). Device user facilities (not physicians' offices) must report deaths associated with the use of a device to the FDA and the manufacturer, and those incidents involving serious injury be reported to the manufacturer of the device. FDA is also requiring distributors of medical devices to report deaths, serious illnesses and serious injuries to FDA that are attributed to medical devices. Distributors are also required to report certain device malfunctions to the manufacturer and to submit an annual report to FDA which certifies the number of medical device reports filed during the preceding year, or that no reports were filed (21 CFR 804).

Notification; Repair, Replacement or Refund; Mandatory Recall and Tracking

The Food and Drug Administration can order manufacturers to notify the public of any product defect that represents a health hazard, and can order manufacturers to repair, replace, or refund the cost of these defective devices. In those situations where there is a reasonable probability that continued use of a device would cause serious injury or death, FDA can issue an order to cease further distribution and notify consignees of our concerns. After an opportunity for a hearing, FDA may amend the order to vacate it, order the modification of the device to eliminate the risk, or order the recall of the device. Firms must conduct audits to assure their system is effective and will be capable of locating possibly defective devices in case of a recall situation.

Banned Devices

FDA may issue a regulation banning any device that presents a substantial deception or substantial unreasonable risk of injury or illness. Where a change in labeling may suffice, manufacturers are provided the opportunity to correct the device's labeling before a ban is initiated. Where a device presents an unreasonable, direct, and substantial danger, FDA may order the ban to take effect upon publication of the proposed banning regulation.

Investigational Devices

Devices that qualified experts use on human subjects, to conduct investigations of their safety and effectiveness, are considered "investigational devices" (Sec. 520(g)). Sponsors who wish to conduct these investigations can be granted exemptions from certain requirements of the Federal Food, Drug, and Cosmetic Act that would otherwise impede these studies by filing an application for an Investigational Device Exemption.

Custom Devices

Certain devices ordered by members of the health professions to conform to their own special needs or to those of their patients are considered custom devices and are exempt from registration and from otherwise applicable performance standards or premarket approval requirements. The exemption applies only to devices not generally available to or used by other health professionals. Custom devices are not exempt from other provisions of the Federal Food, Drug, and Cosmetic Act and regulations.

Imported Devices

Manufacturers of finished devices for importation into the United States are required to comply with Good Manufacturing Practice Regulations. If the manufacturer does not comply with these regulations, their devices may be detained. If the shipment is the initial importation of the device into the United States, the initial importer is required to file a premarket notification with the Food and Drug Administration. However, the Agency will accept premarket notifications from foreign manufacturers.

Requirements of Laws and Regulations Enforced by U.S. FDA - MEDICAL DEVICES
copyright 1999-2000 by Dan Zrymiak and Management Science Institute