Medical device manufacturers may need to re-think their approach to demonstrating substantial equivalence (SE) in the 510(k) notification process, due to the FDA’s recent finalization of the guidance document “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications.” The release of the final version of this guidance cements certain changes to the core of the 510(k) program namely, FDA’s determination to disallow the use of ‘split predicates’ (using one predicate device for its intended use and another predicate device for technological characteristics), and its intention to require much more detail and specific information to be presented in the 510(k) Summary.
Although it is generally agreed that little has changed between the draft version (released December 27, 2011) and the final version, it should be noted that the final guidance document focuses only on the traditional 510(k). FDA announced that it will address and finalize the sections from the draft guidance on special and abbreviated 510(k)s in separate documents. The final guidance document also does not address combination products.
The new guidance includes non-binding recommendations that set out FDA’s current thinking on:
- the appropriate use of multiple predicates (Section IV.C);
- the processes associated with determining whether a new device with new indications for use has a new intended use (Section IV.D);
- the process for determining whether different technological characteristics raise different questions of safety and effectiveness (Section IV.E);
- when performance data, with special emphasis on clinical performance data, may be necessary to support a SE determination (Section IV.F); and
- how to develop 510(k) Summaries to promote greater transparency in the 510(k) decision-making process (Section IV.G),
In addition, the guidance also offers updated information in its appendices:
- Appendix A contains a new 510(k) Decision-Making Flowchart, which FDA states that it has revised in an attempt to simplify the flowchart’s visual structure and to incorporate certain terminology changes from amendments to section 513(i) of the FD&C Act.
- Appendix B uses a point-by-point narrative format to describe the Requirements for a 510(k) Summary taken from 21 CFR 807.92.
- Appendix C is a new Sample of a 510(k) Summary that FDA considers to be compliant with 21 CFR 807.92. The Sample Summary provided in the final guidance document is a robust, detailed and rather lengthy template. It follows FDA’s trend of requiring much more information and transparency in a traditionally sparse and generalized (because publically available) document.
- Appendix D contains a Glossary of Significant Terminology utilized in the final guidance document.
The fact that this document contains very few changes from the draft is a reminder to medical device manufacturers to pay attention to the following major points:
- A 510(k) submission should not rely on ‘split predicates.’ FDA states that Decision Points 1 – 4 in the Flowchart should be established with one device.
- A primary predicate device should be clearly established even though multiple predicates or more than one indication for use under one intended use are allowed.
- In cases where a medical device has successfully advanced through Decision Points 1 – 4 on the Flowchart with a single predicate device, submissions may be able to utilize an appropriate ‘reference device’ (and an accompanying scientific rationale justifying its use) to support scientific methodology or standard reference values at Decision Point 5a.
- Once FDA has determined the indications for use of a new device upon review of its proposed labeling, FDA may rely upon relevant clinical and/or scientific information that does not appear in the proposed labeling submitted with the 510(k), regarding the safety and effectiveness of those indications for use. For example, FDA may rely upon publicly available scientific information or Agency knowledge about how a disease progresses to determine whether indications for use to treat a certain disease or anatomical site constitute a new intended use.
FDA acknowledges that a new medical device does not need to be identical to its predicate in order to be designated as SE. The guidance document states that it is ‘rare’ for a new device to be identical to a device that is currently on the market. Companies must carefully navigate FDA’s requirements for demonstrating and documenting SE.
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