The Framework for Adding Software to Drug Labels: Q&A with Marty Culjat

Marty Culjat
SVP
Global head of digital medicine
and regulatory innovation
EVERSANA

FDA recently proposed new draft framework for prescription drug use-related software (PDURS), or software being added to a drug’s label. EVERSANA’s SVP and global head of digital medicine and regulatory innovation Marty Culjat spoke with Pharmaceutical Executive about the framework and how it may impact the use of this technology.

Pharmaceutial Executive: What does FDA allow in regards to adding software to drug labels?
Marty Culjat: Up until now, there have been no viable methods to formally pair software to a drug. There are many branded companion apps today that are intended to support patients for functions such as injection training, medication reminders, or copay and refill support. There are also regulated digital solutions that are intended to be used alongside a class of drugs, such as insulin dosing calculators and digital therapeutics that must be used adjunctively with prescription drugs, such as Pear Therapeutics’ reSET-O (with buprenorphine) and Otsuka’s Rejoyn (with anti-depressants).

The only way to formally pair software to a drug that provides clinical value to patients has been with a combination product. However, the risk and rigor of combination products has been too high – so much so that there still isn’t a single example of an FDA-approved drug-software combo.

Fortunately, the FDA has introduced a new framework which was originally created to foster innovation with prescription drug use-related software, or PDURS. Recent draft guidance from the FDA now enables software to be added onto the drug label, specifically in the clinical studies section of the prescribing information, if the manufacturer can demonstrate that the software provides a clinically meaningful benefit to the drug. This would allow a provider to optionally prescribe the software to a patient along with the drug.

PE: What are some examples of software being added to drug labels?
Culjat: This PDURS guidance was issued at the end of 2023. It is still in draft form, but several large pharmaceutical companies and digital health startups are exploring solutions and have begun to engage with the FDA on this. Although the guidance talks about both device-connected software and standalone software, pharma companies are most interested in standalone software and software with unregulated wearables, such as smart rings and watches.

The examples under development focus primarily on four areas: personalized dosing solutions that can optimize treatment plans; side effect management solutions that can improve tolerability and safety for brands with serious risk profiles; behavioral support solutions that use digitized behavioral therapies to influence lifestyle change; and digital prognostics that can be used to predict disease severity and flares. The common theme in many of these is that they are gathering active and/or passive patient inputs to optimize or improve treatment. 

PE: What impact will this have on the life sciences industry?
Culjat: If all goes well with the final guidance, this is expected to unlock a new commercial model for startups and software developers in the digital health space who have generally struggled with reimbursement and commercialization. Specifically, it opens the door for meaningful partnerships with the pharma industry when a brand has an unmet clinical need that can be addressed with a digital solution. You might even say this is a lifeline for startups who have pharma-adjacent digital solutions. All that said, I should caution that there is no direct reimbursement necessarily tied to PDURS yet. The value generally comes with a commercial uplift to the brand.

For the pharmaceutical industry, this could be a catalyst. Large pharma has had so many ups and downs with digital over the past several years. There is no question about the value that many of the intended uses described above can bring to patients. However, until now, the regulatory burden to build these solutions, anti-kickback laws that have restricted the distribution of digital companions, and the inability to promote the value of digital companions, have all been a hindrance.

PE: What are the benefits of adding software to drug labels? What are the risks?
Culjat: Aside from the clinical benefits as noted earlier, there are many potential commercial benefits. The first is brand differentiation in competitive markets. For example, when there are multiple drugs in a class that all have a similar safety gap, if one can mitigate that gap with PDURS it immediately has a competitive advantage. Treatment duration is another big one – if you can better manage the side effects and tolerability of a drug, patients will naturally be more adherent and stay on therapy longer. Branded products with PDURS solutions can also help to maintain their elevated value compared to generics. And for brands approaching loss of patent exclusivity, PDURS could be a way to maintain brand demand.

The PDURS framework is “live” now in that one can engage on PDURS with the Agency today, and it is moving forward into final guidance in the next year or so.

However, there is some risk that the final guidance may move away from the FDA’s original intent of fostering innovation. The biggest question is what type of clinical evidence will be required for a PDURS to demonstrate a meaningful clinical benefit to a drug – the expectation and hope is that this will be a fit-for-purpose approach based on the benefit/risk profile and intended use, with lower risk PDURS being able to utilize phase 4 studies and/or real world data that do not put the drug itself at risk.

There are logistical questions about how this will work in practice, such as how a PDURS will be prescribed. There are also questions about how the anti-kickback statute applies to PDURS in different scenarios – initial informal legal opinions on this are positive, and groups such as the Digital Therapeutics Alliance (DTA) are working on building industry consensus so that we can approach regulators and get out ahead of these concerns.

For anyone interested in seeing PDURS make a big impact, now is a great time to jump in with the DTA to help build this industry consensus. For pharma manufacturers interested in exploring how PDURS can impact their pipeline and building a PDURS strategy, now is also a great time to initiate that assessment. In either case, feel free to reach out!This could be the single most impactful initiative at the intersection of digital and pharma in years.