The concept of Substantial Equivalence is existing since mid-1976 when 510k was created. But what is that a 510k? (I should write it 510(k) process, but I prefer to remove the bracket to make it more business casual)

What is a 510k

510(k) is a Premarket Notification outlines in 21 CFR 807 Subpart E . It is used to classify individual post-amendment devices:

Either find a device substantially equivalent to a predicate; or

Find a new device that must be placed automatically into class III and require PMA, de novo, or reclassification before marketing in U.S.

So you can see that the predicate is an important part of the success of the 510k. If you cannot find a predicate you are following a more stringent regulation.

When is a 510k required?

A 510k is required when:

Introducing a device to the U.S. market for the first time

Changing a device’s indication for use/intended use

Making modification(s) to device that could significantly affect safety or effectiveness

But it’s not required when:

It’s a Private Label Distributor who does not modify the device or labeling; or adds company name or language like “distributed by…”

Re-packager or re-labeler who does not alter the labeling

Not selling device in U.S.

Manufacturer of parts

Did you know? 510k submissions are assigned a “K number” – the letter K followed by six digits. If you have a closer look at those number you will notice that, the first two digits indicate the year it was submitted to FDA for review. The next four digits are sequential starting at 0 and indicate the order in which the submission was received. As 510k started on 1976, the first of it is the K760001. The owner of it is Zimmer (now called Zimmer-Biomet). One other story is about the number K000001. It’s the first 510k issued on 2000. And the winner is Boston Scientific.

Now that you know more on what is a 510k process and when to start it, let’s focus on one big part of the process which is the “Substantial Equivalence to a Predicate”.

Why is that so important?

Let’s start with some statistics to help you understand why you should really focus more on the Substantial Equivalence.

75% of 510k are rejected at the first submission to FDA Out of those rejection, 85% are rejected specifically because of Substantial Equivalence issue during the scientific review



It’s one of the 2 key component of the 510k.

To have a successful 510k you need to show: a very strong “Substantial Equivalence” a solid risk mitigation strategy



I think this is not to be neglected. Industry should take really a deep breath and dig on it.

From our side, let’s dig more on the meaning of Substantial Equivalence.

What is substantial equivalence?

Many industry think that this is a no-brainer. But as you can see on previous statistics, it’s not as simple.

What is the official definition from FDA?

Substantial Equivalence Definition: LINK (i)(1)(A) For purposes of determinations of substantial equivalence under subsection (f) and section 520(l), the term “substantially equivalent” or “substantial equivalence” means, with respect to a device being compared to a predicate device, that the device has the same intended use as the predicate device and that the Secretary by order has found that the device (i) has the same technological characteristics as the predicate device, or (ii)(I) has different technological characteristics and the information submitted that the device is substantially equivalent to the predicate device contains information, including appropriate clinical or scientific data if deemed necessary by the Secretary or a person accredited under section 523, that demonstrates that the device is as safe and effective as a legally marketed device, and (II) does not raise different questions of safety and effectiveness than the predicate device. (B) For purposes of subparagraph (A), the term “different technological characteristics” means, with respect to a device being compared to a predicate device, that there is a significant change in the materials, design, energy source, or other features of the device from those of the predicate device.

How can I interpret the definition of Substantial Equivalence?

So a device must be compared to a legally U.S. marketed predicate device that does not require a PMA, i.e.:

A pre-amendment device

A device found by FDA to be Substantially Equivalent

A reclassified device

A device classified by a de novo petition

For the regulatory affairs departments or consultant working on a 510k dossier, they need to define how similar are the product that they want to market in comparison to the predicate that they choose.

How can we do that?

What is the reason to get a rejection?

The main reason for a rejection is only because your failed to convince the FDA. If you follow my previous advice, you should then present your data on a better way.

At the end, it’s not a matter of right or wrong. It’s a matter to convince the FDA. You should sell the regulatory logic to the FDA. Transform yourself to a sales person for your organization and put all the chance on your side. Put your Substantial Equivalence on a gift package for the agent.

If you are not good to do that, you can even be pushed to a more rigorous regulation. Clearly, you need to create a story and imagine all the question that the agent can ask himself. Playing devil advocates can be good. Let’s say that you do that with a colleague. One should try to find a way to reject your file and you can use his arguments to improve your copy.

Example of scenario

Let’s imagine that moment. The scenario that can happen to you, but I really hope that this will remain a possibility for you.

You inform your manager that your reached a milestone and that you are ready to submit your 510k to the FDA. You push the SEND button on your compute and the clock start. Day after day you are looking at your email box. Each time you see FDA, you think this is the answer. And after 9 months you receive THE Email. You open it. And it says, “we have the regret…”. You remember the emails or letters you were receiving when you applied for a job. They mainly all started by this kind of sentence. If you were like me, you stop there and don’t read the rest. Oh my god! They rejected your dossier. What was the reason mentioned? Because of “Substantial Equivalence”.

If this happen, this would be really bad. You waited so long for that. What will you say to your Manager now. He needs this dossier to launch the design of a common product. Did you anticipated this answer? Are you able to respond back immediately or should you spend one more month to think of how to solve the problem?

What are the consequence of a rejection for your company?

The consequence of a rejection can be:

Delay to put your product to the market

Waste of money (No sale, more work on the dossier)

Risk to be pushed to a PMA

So think really carefully when you have to tackle this section of the file. Don’t think that just mentioning a competitor product which look similar will be a Bingo. Instead of praying that this pass, make everything possible so that it doesn’t fail.

Step 1: Separate the main components

A lot of industry are mixing labeling or intended use and technology when it comes to Substantial Equivalence. One good practice is to address “intended use” and “technology characteristics” separately.

Intended use

First FDA will check if both device have the same intended use. So the technique is to create a matrix where you will compare both products.

As I like color coding, I would recommend you to highlight with color the different words.

For example like a traffic light:

Green: Wording is similar and have the same meaning

Wording is similar and have the same meaning Yellow: Words are similar but the meaning can be a bit different

Words are similar but the meaning can be a bit different Red: Completely different words or different meaning

If you see a lot of Green than this is a good sign. But if you see a lot of Red, maybe this is not a good predicate or if there no other predicate then it could become a “de novo”

Technology characteristics

Then I create a technology matrix where we compare both technologies. Same method. I highlight with different colors the wording. I will emphasis differences and similarities.

Additionally, you need to be more specific and include some data, or perform testing. or identify a range of parameters on both products.

More similarities you can show more probably the Substantial Equivalence will be confirmed.

Some industrial are not putting themselves on the shoes of the Agent. He do have tons of files to review, with tons of pages. Sometime I noticed that a lot of submission come in with raw data, without any explanation. The Agent will really not spend time to try to interpret some tables with lot of number. It’s not a good approach and the perception of your file and company will be really bad.

To put yourself on the shoes of the Agent you should tell a story and make his life easier. Remember when you were in College and performing an essay. You should start with an introduction, develop some argumentation with all the information that you’ll get from your matrix and then finalize with a conclusion. It should be a readable document and easy to understand. If the Agent is able to understand everything, the result for you will be better.

Step 2: Analyse the Product Code

The second aspect is also to look at the Product code of the predicate.

If the product code of my predicate is ABC. Then my product should be the same ABC. I should use the same technology for this product code.

What is a Product Code? An FDA product code describes a specific product and contains a combination of 5 to 7 numbers and letters. The easiest way to identify the product code is to get more familiar with the product itself. You should check the label, the processing information, the intended use of product, the container type, who will use or consume the product, etc. The product code has 5 components: Industry code: Broadest are into which a product falls

Broadest are into which a product falls Class code: Only 1 letter and directly related to the industry

Only 1 letter and directly related to the industry Subclass: It’s also 1 letter. It describes the primary material that should contact and/or holds the product

It’s also 1 letter. It describes the primary material that should contact and/or holds the product Process Indicator Code (PIC): It’s again 1 letter. Some industry as Medical Devices do not have a PIC and are represented with hyphen

It’s again 1 letter. Some industry as Medical Devices do not have a PIC and are represented with hyphen Product (Group): 2 characters in length with letters or numbers. Relates directly to an industry/class combination.

Example of medical device product code

Product: First Aid Kit including drugs

Product Code: 76–RR Product Code

Structure Industry Class Subclass Process Identification Code (PIC) Product Format Number Letter Letter or Hyphen (-) Letter or Hyphen (-) Letter or Number Sample 79 L Hyphen (-) Hyphen (-) RR Meaning General & Plastic Surgery Kit Kit, First Aid

Read also: Review all the FDA information on the product code Review all the FDA information on the product code LINK

It’s important to identify it on your predicate and check the similarity with your product.

Same technique. I want to do all what I can to remove all the possibility for FDA to come back to me and reject my 510k.

Step 3: Is it really the right classification?

Classification justification: Create a few paragraph why my device is this classification.

It’s sometime obvious to think that the product has the same classification as the predicate. But don’t assume it, I would recommend to justify it even with 1 sentence on your dossier. This will help to confirm it and also will help to stress on the similarities.

Remember, our objective is to stress the similarity and reduce focus on differences. What I would like you to do is to mitigate the differences or to dismiss them.

Step 4: What are the rules for a Predicate

Regulation says in order to have 510k you should have a predicate, but it doesn’t say how close the technology or how old the predicate should be. I would have a predicate as close as possible to the product and as recent as possible.

Example: If a predicate was in the market a year ago and another one 10 years ago. If the one marketed 10 years ago is more suitable you should use it.

But one other technique that can help you is to explain also on the 510k that a predicate marketed 1 year ago exist. And you should explain why you will not consider it for your file. This will also show to the Agent that you really made a deep dive and not only selected any existing predicate.

Remember, regulation doesn’t say how old the predicate should be. It’s up to us to decide. Regulation is not micro-managing us which is good. We still have the choice to take any product that we think is similar to ours.

Examples of Substantial Equivalence analysis

For those that like simple explanation, I want to give you an example from your daily life.

Imagine that you need to define Substantial Equivalence of a Car with a Truck as a predicate. How would you do that?

First let’s review the similarities. Both have:

an engine

Wheels

Frame

Brakes

Seats

Work with fuel

Need someone to drive them

Go on roads

Have lights

Can transport stuff

Second let’s review the differences

A car have 4 wheels and Truck can be a 18 wheeler

Cars use regular gas when Truck use gasoline

A car can transport few luggage when trucks can transport lot of goods

Car weight less than a truck

…

Obviously, you will focus on the similarities. But if we want to reduce the gap on those difference we can also take a predicate on the same family. Example a Pick-up truck. It’s really closer to a car than a 18 wheeler.

Substantial Equivalence Poker Face

As a sales representative of your company, your mission is to show all the similarities and to not draw attention to the differences.

Maybe a strategy that you would choose is to not talk about the differences.

I would say this is possible. Maybe the agent will not notice them. But If you’re going that way, I should really advice you to work on the argumentation anyway. In case the difference are noticed you need to also show that you are a professional and already anticipating these questions.

This is a poker game but it’s how it works. Industry should sometime take risks but reduce them as small as possible t put all the chances on their side.

How to help the industry?

To summarize the strategy:

Separate Intended Use and Technological Characteristics review

Include an analysis of the product code

Don’t forget to confirm the classification

Take a predicate that is really close to your product even if it was marketed 10 years ago

If a recent similar product exist on the market and it’s less relevant than an old one, mention that on your file

Sell your SE with a storytelling

If you want to play poker, be sure to prepare yourself to answer back in case of more questions.

Finally, remember that a 510k can be kicked back not because you are wrong but because you are not convincing FDA.

I hope this article helped you to have a better understanding of the Substantial Equivalence. I wish you a lot of success on your submissions.

Reference: FDA Guidance: The 510k program: Evaluating Substantial Equivalence in Premarket Notification (Version July 28, 2014: The 510k program: Evaluating Substantial Equivalence in Premarket Notification (Version July 28, 2014: LINK

Medical Device expert. Monir founded Easy Medical Device to help Medical Device companies to place compliant products on the market. He proposes his consulting services so don’t hesitate to contact him at info@easymedicaldevice.com or +41799036836 My objective is to share my knowledge and experience with the community of people working in the Medical Device field.