Digital Therapeutics and Prescription Drug Co-Promotion Compliance

Digital Therapeutics and Prescription Drug Co-Promotion Compliance ⟦c1⟧.

DTx-Drug Co-Promotion as a Compliance Problem MLR Teams Cannot Delegate Away

Prescription digital therapeutics are no longer a side experiment sitting next to the drug pipeline. As more of these products get paired with prescription drugs under formal co-promotion deals, the combined offering picks up two regulatory regimes at once: CDRH oversight for the software itself, and OPDP oversight for how it gets promoted⟦c4⟧. The device and software layer that a DTx brings into the room asks questions those teams were never set up to answer⟦c5⟧. Pairing a PDT with a drug does not divide the compliance work between two calmer, simpler problems ⟦c4⟧⟦c6⟧. It multiplies it into one harder problem, and the rules that are supposed to govern that harder problem are still being drafted⟦c6⟧. Prescription digital therapeutics (PDTs) are moving from pilot programs to commercial scale (Grand View Research valued the global DTx market at USD 7.67 billion in 2024, with Precedence Research placing PDTs at 29.40% market share by product type in 2025 ⟦c3⟧).

PDTs and PDURS: the compliance distinction

That's a device classification, plain and simple. But not every app that sits near a drug counts as a DTx, and the category that actually triggers the compliance questions this piece is about is called prescription drug use-related software, or PDURS: software disseminated by or for a drug sponsor that produces output tied to that sponsor's drug, whether by supplementing it, explaining it, or otherwise connecting to it in text⟦c8⟧. What happens next depends on what evidence the sponsor brings forward. Submit proof that using the PDURS leads to a clinically meaningful benefit, and FDA treats the output as required labeling, subject to the agency's own review and approval⟦c9⟧. Skip that evidence, and the output typically gets treated as promotional labeling instead, which is the fork in the road that matters most here, because it drops PDURS straight into OPDP's jurisdiction⟦c10⟧. PDURS is a draft guidance category right now, not a finalized statutory definition, and FDA still hasn't issued a formal regulatory definition of "prescription digital therapeutic," a gap AMCP has flagged directly in its own policy recommendations⟦c11⟧. Click Therapeutics' Rejoyn, developed with Otsuka for major depressive disorder, and its migraine product CT-132, are both FDA-authorized examples that make the category concrete, even without settling every question about how each one gets classified going forward⟦c12⟧. PDTs are defined as software-based therapies that deliver a clinical benefit either alone or in combination with other treatments, and are regulated by FDA as Software as a Medical Device (SaMD) under Section 201(h) of the FD&C Act ⟦c7⟧.

The PDURS guidance journey as of September 2026

FDA put out its draft PDURS guidance in September 2023, and it holds a specific distinction: it's the first FDA guidance document to address the meeting point of digital health and pharma from a commercial angle, rather than a clinical-trial one⟦c13⟧. As of a report from Inside Health Policy, that guidance had just advanced to the White House Office of Management and Budget for review the week before, a real procedural step, though still a step short of finalization⟦c14⟧. None of that changes the basic fact that the guidance has sat in draft form for roughly three years, and during that entire stretch, co-promotion deals got signed, promotional materials got reviewed and cleared, and products launched, all without a finished rulebook to check against⟦c16⟧. Other pieces of the regulatory picture keep moving too. CDRH's FY2026 guidance agenda lists planned guidance on clinical evidence for digital mental health treatment devices, including computerized behavioral therapy devices, a topic Hogan Lovells calls well-timed given how boom-and-bust this sector's cycles have been⟦c17⟧. And on January 6, 2026, FDA issued updated guidance on clinical decision support software and general wellness devices, with Commissioner Makary describing the changes, per Latham & Watkins, as the agency getting "out of the way as a regulator ⟦c18⟧." The lesson for anyone running review right now is straightforward. A draft guidance that has reached OMB is still a draft, not a rule, and review processes need to be built sturdy enough to hold up through that gap, not just for the day the rule finally lands⟦c19⟧. The American Telehealth Association characterized PDURS as both "de-regulatory" (supporting pairing of software and drugs without the traditional combination product framework) and "deflationary" (enabling integrated solutions without added system cost) ⟦c15⟧.

Where compliance responsibility lives in co-promotion deal structures

Big pharma companies generally don't move at software speed, and the DTx sector has grown around deal structures that hand R&D to one partner and commercial responsibility to another, a split that HLC's writing on pharma-DTx collaborations lays out clearly⟦c20⟧. The clearest working example is Boehringer Ingelheim's partnership with Click Therapeutics on CT-155, a digital therapeutic for schizophrenia⟦c21⟧. Under the original 2020 deal, Click and Boehringer shared R&D duties, but Boehringer held exclusive worldwide rights to commercialize the product, which put promotional compliance squarely on the pharma side of the table⟦c22⟧. MobiHealthNews reported the deal at more than $500 million⟦c23⟧. Then, in April 2026, the structure flipped ⟦c24⟧. Under a new agreement, Boehringer handed full product responsibility back to Click, including commercial rights and marketing authorization, while also making a $50 million Series D investment and providing dedicated funding to support Click's commercial launch, according to FierceBiotech⟦c24⟧. That kind of mid-lifecycle reversal is exactly where compliance risk hides. When the party running commercialization changes, promotional labeling responsibility, OPDP obligations, and fair balance requirements shift completely, so materials that were reviewed and cleared under the old structure may no longer reflect who's actually accountable for them⟦c25⟧. This isn't a new pattern, either. Sandoz, a Novartis division, partnered with Pear Therapeutics in early 2018 to commercialize reSET and reSET-O, then walked away from that relationship during a Sandoz reorganization, a documented case of co-promotion fragility that MobiHealthNews covered at the time⟦c26⟧. The shape of it tends to repeat: a pharma partner funds and commercializes for a while, then exits, and the DTx developer is left holding whatever compliance infrastructure the pharma partner built, or didn't bother to build⟦c27⟧. That's why co-promotion contracts need to spell out, in writing, who owns each piece of promotional material once the deal structure changes, for both parties, not just one. Click Therapeutics, for its part, launched Click SE™ in October 2024 specifically in response to FDA PDURS guidance, aimed at developing "software-enhanced drug therapies," proof that the industry is already building commercial strategy on top of a guidance document that hasn't been finalized yet⟦c28⟧.

The dual-classification problem: when one promotional piece triggers two regulatory regimes

A single piece of promotional content in a DTx-drug co-promotion can be two things at once ⟦c4⟧⟦c29⟧. It can be device promotional material governed by CDRH's standards, and it can simultaneously be prescription drug promotional labeling governed by OPDP⟦c29⟧⟦c30⟧⟦c31⟧. King & Spalding's analysis of the PDURS guidance describes the pairing of drug use and software as sitting in "regulatory limbo," and that's a fair description, given that the software itself may or may not count as a regulated medical device, and the drug's approved labeling may or may not have room for digital tools baked into it⟦c32⟧. The guidance tries to draw a line through this, and it's not a clean one. FDA's position is that PDURS end-user output generally counts as promotional labeling and appears in materials outside the Prescribing Information itself, not within it⟦c33⟧⟦c34⟧. At the same time, prescribers need to know about the additional device features that might shape how they prescribe. The guidance, in King & Spalding's phrase, "walks a fine line" on how PDURS content should be reflected in the PI, without giving co-promotion teams a bright-line rule to follow⟦c35⟧. Play that out in an actual review room and the risk becomes obvious. A reviewer trained to check fair balance in drug promotion might sign off on a DTx co-promotion piece and completely miss a device claim that needed its own independent substantiation ⟦c2⟧. A device-focused reviewer, meanwhile, might miss the drug promotional labeling trigger sitting in the same document⟦c36⟧. This isn't an abstract worry confined to rare edge cases. Diabetes is the single largest DTx application area, holding 29.75% of the market in 2024 according to Grand View Research, and it's a therapeutic space already thick with drug-device combinations, insulin pumps, continuous glucose monitors, and medication management apps among them, which makes getting dual-classification review right an urgent problem, not a theoretical one⟦c37⟧.

The impact of 2025 OPDP enforcement activity on teams reviewing DTx materials in 2026

FDA issued more than 70 Untitled and Warning Letters in 2025, and while a lot of that enforcement centered on direct-to-consumer advertising, it reached well past that: HCP websites, corporate webpages, influencer content, earned media, and patient testimonials all drew scrutiny, per ProPharma Group's analysis⟦c38⟧. A handful of recurring themes in that enforcement matter directly for anyone reviewing DTx co-promotion material ⟦c2⟧. Risk information needs to be clear, conspicuous, and neutral, a standard that applies across every format the information is delivered in, not just the primary one⟦c39⟧⟦c40⟧. Claims need substantiation, and that gets particularly tricky when a benefit claim, especially around magnitude of benefit, time to onset, or quality-of-life improvement, comes from DTx clinical data rather than the drug's own trial data⟦c41⟧. Layer structural change on top of that enforcement pattern and the picture gets tighter still. OPDP's Division of Promotion Policy, Research and Operations was eliminated in April 2025, cutting into the agency's capacity to issue new guidance and likely slowing down advisory review timelines⟦c42⟧. Leadership inside OPDP also turned over following that same restructuring, leaving real uncertainty about how consistent review will be going forward⟦c43⟧. A January 2025 executive order known as "One-in-Ten-Out" puts long-standing draft guidances, including several OPDP documents that MLR teams currently rely on day to day, at risk of being withdrawn without much warning⟦c44⟧. For DTx co-promotion specifically, teams can't count on getting a quick informal read from OPDP to settle the novel dual-classification questions their materials raise ⟦c39⟧. Advisory response times are slower now, and the answers, when they come, are less predictable than they used to be⟦c45⟧.

Requirements for an MLR Review Process Built for DTx Co-Promotion

The MLR review, sometimes called the Promotional Review Committee or PRC, exists to check three things: that promotional content matches approved labeling, that it makes no false or misleading claims, and that it satisfies every applicable regulatory requirement ⟦c46⟧. The DTx context stretches all three of those tests in ways a standard drug-only review was never designed for⟦c46⟧. A few gaps need to get closed directly, not patched over. Clinical benefit claims that come from DTx-specific trial data need their own substantiation, separate from the drug's efficacy data, because a co-promotion piece that mixes the two together without clearly attributing each claim is both a fair balance problem and a substantiation problem⟦c49⟧. None of this holds together without the contract doing its part. Co-promotion agreements need to spell out which party owns MLR sign-off at each stage, what happens to material that was already reviewed and cleared when commercialization responsibility changes hands (as it did in the Boehringer and Click reversal), and how the deal handles a regulatory guidance update that lands mid-campaign⟦c51⟧. That last point isn't hypothetical. With the PDURS guidance sitting at OMB as of September 21, 2026, it's entirely possible the guidance finalizes while a current co-promotion campaign is still running, so review processes need a built-in trigger to re-review material the moment that happens⟦c52⟧. Reimbursement adds one more wrinkle. Payers like Premera still treat PDTs for substance use disorder as investigational, per a policy last revised April 1, 2026 ⟦c53⟧. Any promotional material that implies broad coverage or reimbursement for that kind of indication creates a separate false-impression risk MLR needs to catch before it goes out⟦c53⟧. Standard MLR teams may lack a reviewer trained in SaMD regulatory requirements, and reviewing dual-classified material requires both drug promotion and device promotion expertise in the same review ⟦c47⟧. Approved labeling for the drug and the 510(k)/De Novo authorization for the DTx must both be accessible to reviewers, with claims traceable to one or the other rather than conflated ⟦c48⟧. Given FDA's position that PDURS output generally should not be described in the PI, reviewers must verify that co-promotion materials do not inadvertently import PDURS claims into drug labeling territory ⟦c50⟧.

Compliance and regulatory infrastructure tools for MLR teams

Strip away the regulatory detail and the dual-classification problem is, at its core, a workflow and audit-trail problem. MLR teams need to be able to show, material by material, that both device claims and drug promotional claims were checked against the correct reference documents, by reviewers who actually had the right expertise to check them⟦c54⟧. That's what purpose-built promotional review software needs to deliver in this setting. Version control matters just as much, especially with re-review triggers built in for the moment the PDURS guidance finalizes or commercialization responsibility transfers mid-campaign, the exact scenario that played out in the Boehringer and Click reversal⟦c56⟧. And the audit trail itself needs to hold up under scrutiny: if OPDP ever comes asking questions, the documentation needs to show the material was reviewed with full awareness of both regulatory regimes bearing on it⟦c57⟧. More than 70 enforcement letters in 2025 alone, slower OPDP advisory timelines, and a guidance landscape that keeps shifting produce a situation in which the documentation side of a review platform now matters as much as the workflow side, as these enforcement and timeline patterns show ⟦c58⟧. If an untitled letter arrives, the audit trail is the defense⟦c58⟧. Teams evaluating platforms for this kind of work should look for review tracks that can be configured by regulatory classification, reference document management that keeps device authorizations and drug labeling clearly separated rather than lumped together, and workflow rules that can be updated fast when guidance changes, because in this environment, guidance changes faster than most review systems are built to handle⟦c59⟧. Claim-level annotation and reference linking connects each benefit or safety claim to its specific source document (510(k) summary, drug PI, or clinical publication) so reviewers can verify the correct regulatory basis ⟦c55⟧.