510(K) vs PMA: Understanding the Finer Nuances

Medical devices that are to be placed in the United States market must meet the regulatory requirements of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the regulations in Title 21- Code of Federal Regulations (21 CFR) Parts 1-58, 800-1299.

The regulatory controls and marketing pathways depend on the risk of the device – all of which have been designed to drive better safety and effectiveness of the devices within reasonable limits.

The marketing pathways include -

• Premarket Notification (510(k))
• De Novo Classification Request
• Exempt
• Premarket Approval (PMA)
• Product Development Protocol (PDP)
• Humanitarian Use Exemption (HDE)
• Biologics License Application (BLA)

What is the Right Regulatory Process for a Particular Medical Device?

To know the appropriate pathway for each device, the following four steps form the basis:

• Step One: Classifying the device and understanding applicable regulatory controls
• Step Two: Selecting and preparing the correct premarket submission
• Step Three: Sending the premarket submission to the FDA and interacting with FDA staff during review
• Step Four: Complying with applicable regulatory controls, including the establishment registration and device listing

In this context, it is important to understand the difference between Premarket Notification (501(k)) and Premarket Approval, which may sound similar but address different classes of devices. Both require different levels of effort, operational processes (and cost), and documentation and therefore, understanding this difference is critical for faster time-to-market.

Eligibility for 510(k) Clearance: The Details

510(k) clearance from the FDA is required for the marketing of medium-risk medical devices, while PMA (premarket approval) is meant for devices with higher risk, or ones that are novel and have no precedent.

Typically, FDA needs at least 90 days to review and approve Class I devices for use in the United States. Therefore, the manufacturer is expected to submit it accordingly.

In addition to safety and effectiveness, the submission should also demonstrate substantial equivalence to a legally marketed device (section 513(i)(1)(A) FD&C Act) by comparing it with other similar legally marketed devices and supporting their claims with evidence. Such devices are called predicates and they must also have been approved under the norms.

The device can claim substantial equivalence when

• its intended use is the same as the predicate and
• the technological characteristics are the same as that of the predicate

or

• the intended is the same as the predicate and
• though its technological characteristics are different, there is no risk to safety and effectiveness

FDA determines equivalence by reviewing the methods used to evaluate differences in performance data and technological characteristics. The performance data assessed include:

• Clinical data and non-clinical bench performance data
• Engineering performance testing
• Sterility
• Electromagnetic compatibility
• Software validation
• Biocompatibility evaluation

Following the review by the authorities, the manufacturer submitting the device for approval will receive an order in the form of a letter from the FDA. Only upon getting the clearance from FDA can the device be placed for commercial distribution.

The process of 501(k) submission also facilitates the classification of new devices - that is, devices that were not in commercial distribution before May 28, 1976, or not classified as per current-day parameters.

Typically, FDA does not inspect the facility prior to 510(k) clearance. On receiving the approval, the manufacturer can place the device on the market and expect an FDA quality system (21 CFR 820) inspection any time after.

If substantial equivalence is not available, then the submitter may submit afresh with new data, request a Class I or II classification using the De Novo Classification process, petition for reclassification, or submit a premarket approval application (PMA).

FDA specifies who can apply for 501(k). These include:

• Domestic manufacturers who are releasing a new device in the US market
• Finished device manufacturers of the device based on their own specifications and wish to market it in the US. These include accessories to finished devices also and if they are to be sold to the end user as spare parts.
• Specification developers who outsource the manufacturing to a contracting firm and wish to release a device in the US market
• Re-packers or re-labelers who make changes to the labels or whose operations can impact the safety and effectiveness of the device.
• Foreign manufacturers/exporters or US representatives of such companies wishing to introduce a device in the US market

Eligibility for PMA: The Details

PMA submissions take longer to get approvals. The evidence to be submitted is also more as it is applicable to Class III medical devices and requires clinical trial data proving its safety and effectiveness for its intended users.

Since Class III devices are typically used to support or sustain human life and are critical to preventing the impairment of human health, general and special controls alone are considered insufficient for verifying their safety and effectiveness. Except for pre-amendment devices that may require a Class III 510(k), these Class III devices require PMA application under section 515 of the FD&C Act for obtaining marketing approval.

The PMA application must be submitted by the inventor/developer and manufacturer who may be an individual, a partnership, a corporation, an association, a scientific or academic establishment, a government agency or organizational unit, or any other legal entity that owns the rights or has authorized access to the data and other information.

Governed by Title 21 Code of Federal Regulations (CFR) Part 814, Premarket Approval of Medical Devices, a Class III device that does not meet PMA requirements cannot be marketed as it is considered adulterated under section 501(f) of the FD&C Act.

Any device which has no predicate for reference, is governed by a classification regulation in the CFR, and is a high risk, must get an approved PMA before being commercially distributed in the US.

The application must include administrative elements and scientific and clinical data for review and approval by the FDA.

• The submission must be complete, accurate, consistent, include critical information, and be organized well for a quick approval.
• A quality control audit of the PMA application before FDA submission will improve the chances of fast approval.

To improve the chances of approval of devices by providing the right documentation, use a cloud-based quality management system such as ComplianceQuest. It aligns with ISO standards, the foundation of the FDA, and helps with quality audits, documentation, and compliance for increasing the chances of FDA approval.

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