Memorandum

FDA clears Insulet’s Omnipod Dash as ACE Pump, continuing drive to AID interoperability – September 23, 2019

~Three-month FDA review (stealth!); key for smartphone-based Horizon and Tidepool Loop hybrid closed loops; second ACE Pump clearance of 2019 after Tandem t:slim X2 in February

This morning, Insulet announced FDA 510(k) clearance of Omnipod Dash as an interoperable ACE pump (alternate controller enabled) – a key regulatory step towards commercializing automated insulin delivery (AID) systems with interoperable components, secure Bluetooth communication, and smartphone control.

FDA’s review of Dash as an ACE Pump was a little under three months (submitted June 24, 2019) – see the 510(k) listing here. Notably, Insulet kept this FDA submission very stealth – the past three calls shared plans to eventually go for an ACE Pump indication, though this is the first we’re hearing it had already been submitted in June.

Omnipod Dash is now the second ACE pump cleared in 2019, following the creation of this new interoperable insulin pump category in February with Tandem’s t:slim X2. As part of the submission, Insulet had to show that Dash meets the same special controls around cybersecurity, reliable communication, design, and transparency. Similar to the t:slim X2, the cleared indication for Dash states that it reliably and securely communicates with compatible, digitally connected devices, including automated insulin dosing software, and that it can receive, execute, and confirm commands from these devices. Dexcom’s G6 has a similar indication on the iCGM side.

For Insulet, becoming an interoperable ACE pump is a key regulatory step as it works on its two hybrid closed loop systems – Horizon (internal) and Tidepool Loop (partnership). Both of these systems will have smartphone control, where interoperability and secure Bluetooth communication are musts. Horizon is expected to enter its pivotal study in 4Q19 (launch in 2H20), while Tidepool Loop remains in its observational study. See our AID landscape here.

Along with iCGMs (currently only Dexcom’s G6, but FreeStyle Libre 2 could follow soon), ACE Pumps are part of the vision of a plug-and-play, interoperable ecosystem of AID components – where people with diabetes can mix-and-match different devices, companies can more easily integrate pump-CGM-algorithm combinations, and FDA has less regulatory hassle to deal with all permutations. For instance, once an AID algorithm like Tidepool Loop is approved to work with any iCGM and any ACE pump, a variety of devices could quickly integrate – leveraging a single hybrid closed loop algorithm without having to run individual clinical trials and submit duplicative PMAs to FDA. The interoperable paradigm regulates the three components separately and makes it easier to stitch them together, which should unlock faster innovation, more patient choice, more options for companies, and better focus/specialization.

For Insulet, ACE Pump labeling should also offer easier Omnipod integration with other AID algorithms and other iCGMs, should it choose to pursue these as they become available.

  • An “iController” pathway for AID algorithms will be the last step needed for the complete plug-and-play, mix-and-match vision to be a reality. Tidepool (and potentially Tandem/Dexcom with Control-IQ) are working on this de novo pathway with the FDA. In his D-Data talk in June, FDA’s Dr. Alain Silk suggested potential to make the AID controller class II, 510(k)-regulated software with special controls – bringing the entire closed-loop category down from its current class III PMA level, regulating the components separately, and allowing them to be stitched together and updated quickly. Read a complete summary of Dr. Silk’s talk below.

  • For ACE Pumps and iCGMs, formal company agreements are still needed to share device data and update labeling – i.e., ACE Pumps and iCGMs and AID algorithms cannot automatically be used together unless business relationships are in place. That means even if FreeStyle Libre 2 obtains iCGM labeling, Insulet and Abbott would need a business relationship in place. Still, the process will be faster than in the old world of complete “system” regulation, which would require the business piece and a new PMA. As we understand it, incorporating a non-ACE pump into an AID system will still require traversing the rigorous PMA process – a barrier only for Medtronic now.

  • Medtronic is now the only insulin pump company in the US without Bluetooth and an ACE pump interoperable designation; it does plan to submit for both, following its partnership with Tidepool Loop announced in June. Read more in Medtronic 2Q19.

Close Concerns’ Questions

Q: Will Insulet’s Horizon or Tidepool Loop come to market first? How will users weigh the different experiences? How will patients decide between Tandem’s Control-IQ, Medtronic’s MiniMed 780G, Insulet’s offerings, and others?

Q: Will Insulet choose to integrate with other AID algorithms and other iCGMs (i.e., beyond Horizon, Tidepool Loop, and Dexcom’s G6)? For example, could Insulet integrate with the Dexcom-owned Control-IQ algorithm? Will Insulet integrate with FreeStyle Libre 2 and Senseonics Eversense, once they obtain iCGM labeling?

Q: Who will be first with an iController algorithm? Have Tandem and Dexcom submitted Control-IQ as an iController or as a traditional PMA?

Q: Will companies have clear customer service processes for interoperable systems? How much of a challenge will this be with 1,000 vs. 10,000 vs. 100,000 users? How difficult will it be for patients to navigate multiple suppliers?

Q: Will reimbursement/out-of-pocket cost continue to drive uptake of pumps CGM, and AID? Will this be more important than user experience? Which system will offer the most compelling business model and economics? Will Insulet launch Horizon with no upfront cost, similar to Dash?

Q: Will these next-gen AID user experiences drive significantly larger uptake of pumps and CGM? Will the uptake be rapid (1-3 years) or gradual (5+ years)? When we will we see the vast majority of type 1s on AID? Will cost remain the gating factor?

Background: FDA’s Dr. Alain Silk – D-Data, June 2019

FDA’s Dr. Alain Silk (Acting Branch Chief, Diabetes Diagnostic Devices) provided a thoughtful update on streamlining automated insulin delivery regulation via new regulatory frameworks (iCGM, ACE Pump, a potential iController/iAlgorithm pathway). In line with FDA talks over the past year (ATTD 2019, JDRF/HCT Interoperability Meeting, ADA 2018), the focus was on enabling devices to come to market faster, reducing wasted effort, enabling faster AID component updates and innovation, and propelling more patient choice.

  • Dr. Silk emphasized the regulatory advantages of the new interoperable iCGM and ACE Pump device frameworks, contrasting them with the previous class III PMA world. As we’ve heard from Dr. Lias, the class III path for AID (first graphic in the slide below) carried a “heavy regulatory burden,” evaluating the complete “system” and making it hard to update individual components – especially when different manufacturers were involved. Updating a CGM in the old framework, for instance, required three separate PMA submissions, creating a lot of work (for both FDA and companies) and time delays. The entry barrier for small companies was also high in the PMA model, and FDA was seeing “too much regulatory and contractual burden” as far back as the MiniMed 530G. “We don’t want manufacturers spending time on things that don’t add value. [At FDA] we also have limited resources, and we wanted more efficient ways to deal with this.” The graphic below shows how much better the iCGM path alone is in this model, reducing three PMA submissions down to one 510(k)! (The relevant real-world example here is when Dexcom moved from G4 to G5 (one PMA), followed by Animas and Tandem updating their G4-integrated pumps to add G5 (two more PMAs).)

  • Dr. Silk used a new analogy – a men’s suit – to illustrate the difference between system vs. component regulation and the necessary pre-defined integration plans. There is flexibility in combining different suit components (e.g., jacket, pants, shoes), as long as rules are laid out and followed in terms of how the components can be combined. For instance, to match with this pair of pants, a suit jacket has to be blue or black and it cannot have elbow stripes, and the shoes must be black, etc. In this framework, only compatible components that meet certain pre-defined criteria can be mixed-and-matched into a complete suit. Component-based regulation also requires clearly defined separation of responsibilities. When different companies are involved in an interoperable system (e.g., Dexcom, Tandem), there must be processes in place when someone calls with a problem about the system. “If someone calls with a complaint about the outfit, and you are the pants maker, is it that the pants are baggy? Is the jacket cut too high?” We thought this analogy worked really well, illustrating that business relationships and clearly defined integration plans will be critical in the interoperable AID world – it won’t be true mix-and-match like we see in consumer electronics. Still, the regulatory and product innovation advantages are going to be huge, and we imagine most pump and CGM companies will move to this model over time (given the speed and component-update advantages).

  • “We’re 2/3 of the way there... the third part that is absent is the controller. We do think that a class II, 510(k) pathway with Special Controls may be a way to get to regulation of the software controller as a medical device. We are looking for input on this and would like to tap into your collective wisdom. Do you have thoughts on what the Special Controls would look like?” To us, an iController designation seems like a matter of when, rather than if. Who will be first? We also wonder what the Special Controls will be on a class II, 510(k)-regulated AID control algorithm – it is arguably more nuanced than iCGM accuracy benchmarks or ACE pump communication. What parameters will an algorithm have to meet? Will iControllers only be approved to work with iCGMs and ACE Pumps? Will minimum CGM accuracy be required? What algorithm parameters will have to be specified, especially if the algorithm is complicated or a “learning” algorithm that adapts? When will a clinical trial be required for an iController? What sort of algorithm updates would require a new trial vs. a label update and communication plan? What algorithm updates would be FDA reviewed?

Background: Tidepool Loop – Howard Look at FFL, July 2019

Howard Look shared the inspiring Tidepool story and provided an update on Tidepool Loop following the eventful ADA. Download his slides here. As they usually do, Tidepool kept expectations realistic about their hopes for the timing of the Tidepool Loop FDA submission. When asked, Mr. Look said, “We never want to be the company that contributes to mis-set expectations (like ‘a cure in five years’), so we want to keep expectations low. We hope it's measured in months, not years. We let the FDA know that we set an aggressive target of trying to have a submission prepared before the end of the (calendar) year (2019), but there’s a lot that's out of our control, so that's just an estimate. We promise to keep the community up to speed as things proceed.” This reflects fast progress since the October 2018 announcement to build a regulated version of the DIY iOS app, of Insulet joining in November, the Jaeb observational study kicking off in January, and partners Dexcom and Medtronic joining in June. Tidepool meets with the FDA frequently and is currently working on the submission path – will it receive an iController designation?

--by Adam Brown and Kelly Close