FDA Pre-Cert v1.0 Explained: 2019 and the Promises of Years to Come

By Jacob Graham, VP QA/RA & Cofounder of Enzyme. Learn more about Jacob.

This past Monday, January 7th 2019, FDA announced and published documents which form the foundation of the Software Pre-Cert Program: the long-awaited 1.0 version of the Working Model for the Software Precertification Program (Pre-Cert) along with a corresponding Regulatory Framework and Test Plan. The program underwent multiple iterations through the course of the Pre-Cert pilot last year, as FDA worked closely with pilot participant companies and solicited feedback from stakeholders at large. The Working Model will now be tested in 2019 to demonstrate whether the proposed Pre-Cert process for SaMD (Software as a Medical Device) product approvals will yield an equivalent review rigor to the traditional 510(k) and De Novo submission and review processes in determining whether a product is safe and effective.

Fig. 1: A reimagined approach for the regulation of software [Fig. 1 from the Working Model v1.0]

TL;DR Should your company try for Pre-Cert this year?

For a mid-market/enterprise company, there’s potential strategic value in helping FDA better refine the Pre-Cert process and thus having a seat at the table as the program is tested and evolves. Once finalized the program can be promoted to Congress and formalized into law as an alternative marketing approval pathway.

For startups, unfortunately, the additional 2019 Pre-Cert overhead may not be worth it.

We explain why below, but in short participating in this requires doing all the Pre-Cert work AND all the work toward a traditional 510(k) or De Novo submission.

There’s one large exception though; we agree with our colleague David Amor, VP QA/RA at Pear Therapeutics, when he says that Pre-Cert will be unusually well-suited at the outset for companies making AI products.

“If you’re establishing a complex neural network you are going to change based on the data sets that you have and that’s only going to increase as the company progresses in iterating on that model,” Amor said. “In that system you have to have a trust in the organization’s process.”

If this describes your company’s situation and you would like to discuss the pros/cons of doing Pre-Cert this year, please get in touch with us. We’d be happy to help.

What’s this “Pre-Cert” thing again?

All software regulated by FDA is considered a “medical device” and subject to the same general class of regulations as products such as pacemakers, stents or contact lenses. This was fine when the sum total of software regulated by FDA was limited to things like MRI firmware, but software has “eaten the world.” Not only can it be iterated upon much more quickly, the pace of innovation in new types of products such as digital therapeutics and AI-powered diagnostics depends on how quickly they can be iterated upon.

Current FDA medical device approval timelines range from 90 days to 180 days, and delays can double that number; a timeline that is incompatible with modern software development.

Thus, Pre-Cert. Instead of requiring a thorough review of the company and its product for each of its product iterations, FDA proposes to certify a company and its software development process for conformance to Principles of Excellence. Once certified, company products that fall below a certain risk threshold can undergo a “streamlined review” or no premarket review at all.

What do you mean by “test” the proposed Pre-Cert process?

Much as FDA requires companies to demonstrate their products are safe and effective before granting approval, FDA is now in the hot seat to demonstrate their Pre-Cert Program will yield the same decisions as the traditional submission and review processes. Essentially, FDA is using the year 2019 to methodically perform the required testing to provide evidence that the Pre-Cert Program works.

It’s vital that the proposed new process decision (approval or denial) for SaMD products correlates with the decisions from the traditional processes; this ensures the same adequate level of prevention and control of patient risk. A successful test will provide the evidence to lobby congress to grant the FDA these authorities. Multiple Senators have already expressed wariness of Pre-Cert, highlighting FDA’s mandate to safeguard patient safety. So, this evidence will undoubtedly be crucial for any bipartisan support in Congress.

Wait, How will FDA Test a Program They Can’t Yet Formally Implement?

When a company tests a physical product before commercializing it and thereby, usually, destroys samples of the product, the test product is then almost always discarded, having fulfilled its purpose in providing sufficient safety and performance evidence. The built and destroyed product is part of the inherent cost of demonstrating the product is safe and effective. Similarly, FDA must generate the evidence to support the validity of Pre-Cert without yet officially implementing it; there’s no way to avoid an added, temporary, regulatory overhead through this testing. Some of the burden will be on companies, and the rest will be FDA’s.

Additional Overhead?

The Pre-Cert Working Model v1.0 details the primary Pre-Cert premise that a portion of the current traditional submission and review processes can be extracted and reviewed separately — and can then be referenced in future “streamlined” new product submissions or product updates by the company. The review of the submission will then be “more efficient” and presumably faster. Being faster is key because, as FDA acknowledges, the nature of evaluating software and the subsequent versioning process occurs differently from traditional devices as well as on a very different timescale.

The Test Plan for 2019 contains steps that are summarized below in Table 1 which also depicts who the primary owner is (company or FDA), whether it is consistent with the traditional submission/review overhead, or is additional (and whether temporary or permanent).

Table 1: Summary of 2019 Pre-Cert Program steps

As you can see, it’s a mixed bag of existing and additional overhead that will increase costs for 2019 Pre-Cert participants.

Figure 2: RWPA Post-Launch Product Monitoring Domains [Fig. 8 from the Working Model v1.0]

The key aspect is the long-term goal of a more streamlined review process that will (in theory, and hopefully in practice in 2019) be “more efficient”, therefore faster.

What are the benefits of the Pre-Cert Program?

FDA touts the future ‘Streamlined Review’ and ‘No Review’ benefits of the Pre-Cert Program, in particular that they will be more agile and result in patients getting access to new SaMD products and updates to SaMD products in a much faster and more efficient manner. The speed of updates, particularly those that add risk control measures, could be as fast as the company has them ready for deployment (e.g. weekly, monthly). This vision has always been in essence the promise of Pre-Cert, allowing software teams to release FDA-regulated software as fast as they develop it. Ensuring the ability of that timeline for low-risk modifications to products is a key tenet of the Pre-Cert Program.

Something FDA only hints at in the Working Model v1.0 but deserves more air time is that the (future, once implemented) cumulative Excellence Appraisal, Path Determination (and Risk Categorization), and Streamlined Review will on average require lower overhead for both companies and FDA. Given this is the primary future benefit of the 2019 temporary additional overhead required to test Pre-Cert, FDA should provide additional supporting arguments to further convince potential participants of the broader long-term benefits of the program.

There are two aspects to this, and FDA only mentions one. The Excellence Appraisal would apply to all future streamlined review submissions, thereby only requiring it once until significant changes are made in the organization that trigger a new appraisal. So, this benefit applies to all companies that plan to commercialize more than one product (granted, almost all companies — but perhaps not some startups whose efforts may be geared toward mere exits).

Additionally, there is an underlying and significant value of separating considering the Excellence Appraisal, Path Determination (and Risk Characterization), and product-specific submission information individually. There are a significant number of failed submissions that could have succeeded if companies engaged the agency earlier. Pre-submissions are growing in popularity, but the process is still under utilized. With more frequent feedback from FDA, companies can course-correct earlier, reducing their overall product development cost and time-to-market.

We recommend FDA publish current data on submission rejections and estimates on rework for both affected companies and FDA, specifically on what FDA deems were avoidable rejections.

This will add key real data into the benefits assessment of the proposed Pre-Cert Program.

Finally, though not a benefit FDA can admit, 2019 Pre-Cert participants will likely garner some goodwill from FDA in going above and beyond to support the evaluation of Pre-Cert. Participants will be sacrificing resources for the greater good; while there will be no quid pro quo involved, this represents a superb opportunity to develop strong working relationships with FDA. The experience of participation is also a prime opportunity to gain insight into FDA’s thought process and to provide valuable feedback to FDA for v2.0 of the Model.

What’s Next?

After the 2019 Pre-Cert test is complete, and assuming the results are positive, FDA will propose the necessary statutory changes to Congress for permanently implementing Pre-Cert Program. A broader political question is “will Congress be in a position to pass such a law if the decision comes during the 2020 election year?” Further, there is a risk of continued government shutdown further delaying all product reviews and therefore the testing and development of the program. All that said, the Pre-Cert and the FDA Digital Health team, helmed by Associate Director Bakul Patel, have significant FDA leadership support, including Jeff Shuren (Director of CDRH) and Scott Gottlieb (FDA Commissioner). So odds are that the Pre-Cert Program is here to stay.

If you have questions or topics you want us to discuss, email us at info@enzyme.com.

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