Diagnostic companies can use the US FDA Emergency Use Authorization (EUA) for COVID-19 testing to fast-track the approval process; however, they should plan ahead to ensure their product remains on the market after the public health emergency subsides.
Invetech’s Stephen Hess recently spoke with Fran White, President of Regulatory Affairs at MDC Associates, Inc., to discuss this opportunity, how to prepare for EUA submissions, and ways IVD instrumentation companies can plan for an eventual 510(k).
Watch the interview or read the transcript below.
Can you start by giving us an overview of your background?
Sure, I founded MDC Associates 30 years ago with the goal of providing technical support and regulatory consulting to the in vitro diagnostics (IVD) market. We’re probably one of the very few regulatory consulting groups that specializes only in IVD products, and we provide early startup information, quality systems, product development advice, and support for managing and helping monitor clinical trials all the way through to final FDA clearance.
What's required by the FDA for IVD devices under the EUA guidelines?
The EUA guidelines for COVID-19 diagnostic tests are very reduced compared to a normal 510(k) process; many 510(k) elements are not required. The agency (FDA) wants to know your intent to market.
You can do a pre-EUA to give the FDA information as to what and how the product is going to work. And they’ll give you some guidance on the data they’ll want to see. Then, you can submit a final EUA requesting the agency to authorize your product for sale during this emergency.
The agency can cancel that EUA at any time, and then you cannot sell unless you get a 510(k). However, the agency has said that they see this emergency use being in place for quite a long time — much longer than others we have seen.
Requirements are minimal. There are product performance requirements specific to limit of detection (LOD), cross-reactivity and performance with spiked samples.
The agency’s getting closer to asking you to test some real samples. Initially, you couldn’t get your hands on any real samples, but the samples are becoming available, with more testing that’s done. So, the FDA wants to see that.
Things such as software validation, process validation, and other information specific to a 510(k) are not required.
How are the other global agencies dealing with their emergency use?
In Europe, there is no emergency use. You still need to get a product CE marked and the CE mark hasn’t really changed. All these products are self-declared. So the requirements are minimal, but you do have to provide a technical file and provide the information needed in that technical file to get your CE mark.
There is an EUA process in Korea, China and Japan. They each have a different approach, but all are very much the same in the fact that very minimal data is required.
Some companies may start to think, “There’s so many products out there, maybe I don’t need to submit anymore. It’s not going to be worth my while.” But everybody’s talking about testing, a million tests a day, two million tests a day. For serology, people are saying we need three to five million tests a day to see who’s developing immunity.
To date, the majority of the EUAs that have been cleared are either manual products or products that are being performed on platforms that are already FDA cleared with another assay. If you have a brand new platform, you should still submit, but the process may be more difficult.
“If you have a brand new platform, I’d advise doing a pre-EUA as soon as possible to get feedback from the agency as to what they might want to see.”
For those companies, I’d advise doing a pre-EUA as soon as possible to get feedback from the agency as to what they might want to see, because now they’re clearing a platform as well as an assay. Start the discussion with the agency early so you understand the path forward.
Is there capacity at the FDA for a pre-EUA process?
Capacity at the FDA seems to be a real challenge. I think they are trying to keep up with Coronavirus at the expense of any other new product. And especially within the division that is responsible for reviewing COVID-19, which is the infectious disease group at the agency.
And, in my opinion, I think one of the problems is that there are a lot of companies with very little experience pursuing an EUA, so the quality of the submissions has been poor. That makes it much harder for the agency to get these products through and reviewed and cleared because they have to interface with the company and try to help them along.
Aside from the pre-EUA, what should companies do to prepare their submissions?
Plan carefully. Collect the data in a very organized fashion. Do not shortcut the process.
It’s also important to know some general rules about submissions that I think some people without experience don’t know. You don’t just submit a summary of the data. The agency’s going to want to see your line item data, even in the EUA process. They want to see an organized submission saying how you did your studies with a protocol if you can provide it on an outline of how the studies were done.
If you’re going to get samples for serology, indicate where you are going to get those samples. To show specificity, one of the new requirements is that they’d like you to test 75 pre-COVID samples. Those samples are readily available, but you have to decide where you’re going to get them and be able to document that they are pre-COVID.
The FDA defines “pre-COVID” as samples that are collected just before December 2019 in the United States. This is another challenge for international companies because the FDA has very specifically said those specificity samples should be from the US population and only the US population.
“Plan carefully. Collect the data in a very organized fashion. Do not shortcut the process.”
You want to be sure to be clear in your design process. The FDA has said you don’t have to follow all your design processes. You don’t have to validate production. You don’t have to do usability studies. But you want to be sure that you have sufficient design information so that you are collecting what you’re going to need for the EUA. Don’t just finish your design and say, “Now we’re going to test this and go to EUA,” because you will have challenges.
When do you think the FDA will issue guidelines for bringing EUA products through the 501(k) process?
In my opinion, I think maybe within the next three to six months. Companies will need to start planning ahead and thinking about all the things they didn’t have to do for EUA that now will be required for 510(k).
And what you will see is a lot of products are going to drop out and not go for 510(k). And then there’s going to be less competition in the market, which means if you’re going to put in the time to develop a product, you really want to be prepared to do that 510(k) so you can stay in the market.
Is there anything critical to focus on throughout the EUA process to eventually get that 510(k) even though it's not defined yet – especially for IVD instrumentation companies?
Plan carefully. With software or an algorithm, make sure that even if it isn’t required, you’re validating that algorithm. Electrical safety — get your electrical safety done, the agency hasn’t included that as part of the EUA, but plan to meet the EMC requirements.
And once you get your product into the market under an EUA, think ahead as to next steps. Maybe you’re going to have to expand on your analytical testing, do stability testing, or start to think about clinical testing.
And if it’s a serology product, what are you going to compare it to? Are you going to do outcome studies to confirm patients truly were positive? How will you demonstrate product performance beyond EUA?
Know you are going to have to do all this. You just don’t have to do it today.
Can the data that is being collected with patients under the EUA be applied to the 510(k) process?
Absolutely. Work with your sites and see what they’re collecting so that you can start to define and capture that data to help eventually with a 510(k).
Sites have to keep all data since this is a reportable disease. So you, as well as everybody else, has to know their positivity rate. And if they do think they see false negatives, you should be prepared to help them try to figure out why. You must have a system in place for complaint reporting and medical device reporting to the agency. Any adverse event, any complaint received, must go back to the FDA.
Are there any closing comments you'd like to make regarding EUA and the 510(k) process?
To date, the FDA has been very open and helpful. So reach out if you have questions; they will answer them through the email address — email@example.com.
Make sure you have an organized submission to send to the FDA so that you can get through the process quickly and are able to sell your product. MDC Associates Inc. has done some submissions. We structure them as we would structure a 510(k) with a lot of information you would provide that the agency hasn’t asked for, like a CDRH Premarket Review Submission Cover Sheet, comments about your manufacturing process, and comments on previous submissions. There isn’t a big emphasis on quality system regulations right now, but there will be. So I think organization is probably the biggest and most important thing.
“There isn’t a big emphasis on quality system regulations right now, but there will be. So I think organization is probably the biggest and most important thing.”
And don’t just think short-term, “I just need to get this done and get to the agency.” Think about performance and organizing your submission so that you’re ready for the next step.
About Fran White
Fran is President, Regulatory Affairs at MDC Associates and a highly regarded IVD regulatory expert. She founded MDC Associates more than 30 years ago to provide her expertise to the broader IVD industry. Under her direction and leadership, the company has grown and extended service offerings to include quality systems development, managing clinical trials and developing and supporting IVD customer training.