New Final Guidance of 510(K) by the FDA

On July 28, 2014, FDA issued the newest "Final Guidance of The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]" after revised draft guidance issued in Dec 28, 2011. The final guidance gives more examples than the 2011 draft guidance to better illustrate the decision-making process during a 510(k) review. It also includes a sample 510(k) summary which is more much detailed than most 510(k) summary documents found on the FDA website. Special and Abbreviated 510(k) sections were removed. FDA intends to finalize these sections separately. Although FDA states that this guidance is "not intended to implement significant policy changes," the guidance clarifies and addresses many key issues in the 510(k) program.

The US FDA requires that the manufacturers demonstrate safety and efficacy of the product, unless the devicecan be shown to be substantially equivalent (SE) to a predicate product that is legally marketed in the United States (via the 510(k)). For most new products, those without predicates, and certain high-risk products (typically Class III), a PMA is required. Certain Class I and exempted Class II medical devices are permitted to be marketed without the FDA’s prior authorization, although manufacturing(Quality System Regulations) and/or documentation controls may still apply. Some important points are summaried below:

Predicate Device

Predicate device is a the legally marketed device a legally marketed device, which is a device that (i) was legally marketed prior to May 28, 1976 (preamendments device) and for which a PMA is not required; or (ii) has been reclassified from Class III to Class II or I; or (iii) has been found SE through the 510(k) process. Although a manufacturer can identify multiple predicate devices, FDA recommends identifying a primary predicate in the submission.
In the guidance, FDA emphasizes that "split predicate" is not allowed in the submission. Split predicate is a situation in which a manufacturer is attempting to “split” the 510(k) decision making process by demonstrating that a new device has the same intended use as one marketed device while comparing the new device’s technological characteristics with a second marketed device that has a different intended use.

Critical Decisions Points

FDA updates the 510(k) review flowchart that was first introduced in 1986. Accroding to the flowchart in Appendix A of the guidance, the critical decisions points in the decision-making process (flowchart) the FDA uses to determine substantial equivalence are:

1. predicate device legally marketed
2. Do the devices have the same intended use
3. Do the devices have the same technological characteristics
4. Do the different technological characteristics of the devices raise different questions of safety and effectiveness
5. (or 5a), Are the proposed scientific methods for evaluating new/different characteristics’ effects on safety and effectivenessmethods acceptable
6. or (5b), Do the performance data demonstrate substantial equivalence

 

Reference Devices

Reference devices may be used to support scientific methodology or standard reference values at Decision Point 5a after a manufacturer successfully navigates through Decision Point 4 on the Flowchart using a single predicate device. However, a reference device is not considered a predicate device and it cannot be used to address Decision Points 1-4.

Intended Use and Indications for Use

These two terms are easy to be confused.  According to the guidance, the term intended use means the general purpose of the device or its function, and encompasses the indications for use. The term indications for use, as defined in 21 CFR 814.20(b)(3)(i), describes the disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the patient population for which the device is intended. A finding of substantial equivalence means that the indications for use of the new device fall within the intended use of the predicate device and, therefore, the two devices have the same intended use.