8.4: More Regulations

Medical Device Labeling

Any label or written material on the device or material that accompanies the device. Labeling must provide adequate directions for use unless exempt and labeling must not be false or misleading. Labeling must have adequate directions for use, proper operating instructions, and warnings where the device's use may be dangerous. The FDA recognizes three types of labeling for devices. A. FDA-approved labeling. B. FDA-promotional labeling and C. Package-insert labeling. The basic outline for labeling specific to medical devices includes the manufacturer, Device Name, Description, Indication, Contraindications, Warnings, and Precautions, Use in Specific Populations, Prescription device statement, Adverse reactions, and Date of issue. To learn more about device labeling: https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/DeviceLabeling/default.htm

Labeling Enforcement

FDA can enforce labeling violations through Notices of Violation (NOVs), Warning Letters, or judicial action (consent decrees, injunctions, and seizures). The FDA looks at a company's website, videos, commercials, brochures, bulk mailings, and press releases to determine if there is any misrepresentation of labeling a device. The FDA responds to violations with the least stringent action depending on the potential to jeopardize public health.

Misbranding

Section 502 of the FFDCA contains provisions on misbranding and false or misleading labeling. A device is considered misbranded if it is false or misleading in any way and if it does not include adequate directions for use. Other examples of misbranding from the FDA website:

• It is in package form, and its label fails to contain the name and place of business of the manufacturer, packer, or distributor; and an accurate statement of the contents regarding weight, measure, or numerical count;
• Any required wording is not prominently displayed as compared with other wording on the device, or is not clearly stated;
• It is dangerous to health when used in the dosage or manner or with the frequency or duration prescribed, recommended or suggested in the labeling;
• If the device's established name, its name in an official compendium or any common or usual name is not prominently printed in type at least half as large as that used for any proprietary name;
• If the establishment is not registered with FDA as per Section 510, has no device listed as per section 510(j), or obtained applicable premarket notification clearance as per Section 510(k);
• If the device is subject to a performance standard and it does not bear the labeling prescribed in that standard" (FDA.gov).

Quality System (QS) Regulation - CFR 820

"CFR 820 covers the design and manufacture of devices sold in the US and is like ISO 13485. Part of this regulation states manufacturing facilities will be inspected by the FDA. The quality system regulation includes requirements related to the methods used in and the facilities and controls used for designing, purchasing, manufacturing, packaging, labeling, storing, installing, and servicing of medical devices. Manufacturing facilities undergo FDA inspections to ensure compliance with the QS requirements. www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/QualitySy stemsRegulations/default.htm

Code of Federal Regulations (CFR) Citations

• 21 CFR Parts 50, 56, 812: Clinical Studies
• 21 CFR Part 807
  • Establishment Registration and Listing
  • Premarket Notification [510(k)]
• 21 CFR Part 814: Premarket Approval (PMA)
• 21 CFR Part 812: Investigational Device Exemptions
• 21 CFR Parts 801, 809, 812, 820
  • Medical Device Labeling
• 21 CFR Part 820: Quality System Regulation
• 21 CFR Part 821: Tracking Requirements
• 21 CFR Part 803: Medical Device Reporting

The Flexibility of the QS Regulation

"The QS regulation for devices embraces the same "umbrella'' approach to the CGMP regulation of drugs. Because the regulation must apply to so many different types of devices, the regulation does not prescribe in detail how a manufacturer must produce a specific device. Rather, the regulation provides the framework that all manufacturers must follow by requiring that manufacturers develop and follow procedures and fill in the details that are appropriate to a given device according to the current state-of-the-art manufacturing for that specific device.

Manufacturers should use good judgment when developing their quality system and apply those sections of the QS regulation that apply to their specific products and operations, 21 CFR 820.5 of the QS regulation. Operating within this flexibility, it is the responsibility of each manufacturer to establish requirements for each type or family of devices that will result in devices that are safe and effective. The responsibility for meeting these needs and for having objective evidence of meeting these requirements may not be delegated.

Because the QS regulation covers a broad spectrum of devices, production processes, etc., it allows some leeway in the details of quality system elements. It is left to manufacturers to determine the necessity for, or extent of, some quality features and to develop and implement specific procedures tailored to their particular processes and devices" (FDA.gov).

International Harmonization

The FDA has been a strong advocate for international harmonization of regulations. They worked in collaboration with the Global Harmonization Taskforce (GHTF) to develop QSR that promotes incorporation of international harmonization. In 2011, the GHTF re-organized to become the International Medical Device Regulators Forum (IMDRF), which includes representatives from the US, Canada, Australia, Brazil, Japan, and Europe. More information can be found here: http://www.imdrf.org/

ISO Device Regulations - ISO 13485

ISO 13485 is the standard for a quality management system for the design and manufacture of medical devices. Although ISO 13485 is a stand-alone document, it is harmonized with ISO 9001 with a few important exceptions: It does not need to demonstrate continual improvement, and it does not have customer satisfaction requirements. What it does have, is a focus on risk management and design control, which is essential for device manufacturing. ISO 3485 also includes inspection and traceability requirements for implantable devices. It promotes awareness of regulatory requirements but also in-line with IMDRF

Post-Marketing Activities

The FDA requires medical device manufacturers to participate in many post-market activities, maintaining a quality system, inspections, post-market surveillance studies, tracking, reporting device malfunctions and injury, and death.

• Medical Device Reporting (MDR) 21 CFR 803: If a device causes death or serious injury, it must be reported. There are also instances where malfunctions must also be reported and allows the FDA to monitor problems. The report must be made within 30 days, and there is a form and a website called Med Watch.
• Medical Device Recall: A medical device recall is an action that takes place to address a problem with a medical device that may be in violation of an FDA law. Recalls occur when the device is defective; it causes a risk to health or both. A recall does not necessarily mean the product must be returned, sometimes it just needs to be adjusted, or clarification safety instructions provided. 21 CFR 7 provides guidance so that responsible firms may conduct an active voluntary recall.

Examples of the types of actions that may be considered recalls:

• Inspecting the device for problems
• Repairing the device
• Adjusting settings on the device
• Re-labeling the device
• Destroying device
• Notifying patients of a problem
• Monitoring patients for health issues

A recall is either a correction or removal of a product. A Correction addresses a problem with a medical device where it is used or sold; a Removal addresses a problem with a medical device by removing it from where it is used or sold. In most cases, a company voluntarily recalls a device on its own. When the company has violated an FDA law, the company must recall the device (correction or removal) and notify the FDA. Legally, the FDA can require a company to recall a device if a company refuses to do so under 21 CFR 810, Medical Device Recall Authority. 21 CFR 810 describes the procedures the FDA follows in exercising its medical device recall authority under section 518(e) of the FD&C Act. It is important to note that a recall does not include a market withdrawal or a stock recovery. When there is a minor infraction not subject to legal action, the FDA may approve a market withdrawal. In the end, almost all recalls are conducted on a voluntary basis by the manufacturer.

A list of recalls by date, https://www.fda.gov/Safety/Recalls/, and a comprehensive searchable recall device database www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm

Device recalls following the same general recall procedure as previously discussed for drugs, which includes classification of recall (I, II or III), developing a recall strategy, and providing the FDA with recall status reports. To learn more about Device Recalls, visit the FDA device recall web page, and watch the FDA Video: http://fda.yorkcast.com/webcast/Play/1b95461f64be40ecbe3415195cb394911d