By Manny Jurado, Principal, Director of Digital Health & Access Innovation Strategy, The Dedham Group, Austin Speier, Chief Strategy Officer, Click Therapeutics, and Steven Lee, Director, Strategy, Click Therapeutics
In September 2023, the FDA released a new guidance document titled Regulatory Considerations for Prescription Drug Use-Related Software (PDURS). This guidance outlines how the FDA intends to apply its drug labeling authorities to software outputs associated with prescription drugs or drug-device combination products. It also opens several opportunities for brand differentiation and commercial success. Here’s what pharma manufacturers need to know about this guidance and how to prepare.
Understanding the PDURS Guidance
The PDURS guidance reflects the FDA’s current thinking on how to regulate software that is used in conjunction with prescription drugs. This includes software that might offer additional clinical benefits when used alongside a drug. For instance, studies have shown that digital health interventions like virtual reality, wearables, and apps have improved care and outcomes for patients with Alzheimer’s disease and dementia, and apps also have helped monitor mental health conditions like anxiety and depression. A video game for oncology patients increased patients’ treatment efficacy, and apps for rheumatoid arthritis patients have helped them get information about the disease, track disease progression, and encourage healthy habits.
The PDURS guidance’s section on added clinical benefit is particularly significant. It indicates that manufacturers can now incorporate data demonstrating the added benefit of their software directly into the drug’s package insert, providing a clear regulatory pathway for integrating software with existing drug products.
The guidance was issued in draft in September 2023 and is open for public comment until final guidance is issued, potentially in September of this year, though it may take longer. During this period, manufacturers may still engage with the FDA to discuss how PDURS could apply to their products, even though the guidance is in draft form.
Why this Differs from Previous Digital Health Opportunities
While opportunities for digital health in pharma have been under discussion for years, the arrival of the PDURS guidance marks something entirely new. The FDA has now indicated that manufacturers can combine software with drugs to demonstrate added clinical benefits directly in the drug label. This effectively allows for ‘digital dosages’ of drugs that can be tied to new or enhanced treatment claims. We anticipate that as soon as one drug establishes such additional clinical claims for a digital dosage in a competitive class, it will become table stakes to offer a digital dosage in that category. Furthermore, this opens new opportunities to improve existing and legacy drug products over time, since digital dosages can be added later in a product’s lifecycle, and the digital dosage itself can be iterated on over time (v1.0, v1.1, v2.0, etc.).
Importantly, the issuance of this guidance coincides with the arrival of a new generation of well-validated and FDA-regulated digital treatments that are increasingly showing robust evidence of clinical benefit on top of background pharmacotherapy. These products are developed under standards for software-as-a-medical-device, creating regulatory certainty and greater reliability for digital offerings, and covering diverse compliance needs such as cybersecurity and artificial intelligence. These products are particularly well-suited for adaptation to the FDA regulatory paradigm for drugs and so can meet the compliance and quality needs of global pharmaceutical companies. It’s a break from the digital offerings of the past, which were developed more as optional tools for patient convenience (e.g., co-pay or patient assistance programs) or clinical research tools (e.g., digital endpoints in clinical studies).
Preparing for PDURS: Strategic Implications
The new guidance presents several opportunities and challenges for pharma manufacturers. Here are some key aspects to consider:
- Clinical benefit demonstration: The PDURS guidance has given pharma manufacturers more leeway to differentiate their drug and biologic products by adding software-based benefit claims to product labels. To do so, manufacturers need to conduct at least one adequate and well-controlled clinical study to demonstrate the clinical benefits of their software. Exact evidence requirements will need to be determined on a per-product basis in consultation with FDA. Studies may include traditional randomized controlled trials or potentially more innovative designs, such as use of Bayesian approaches leveraging historical controls (e.g., existing drug-only clinical data). Real-world evidence might also play a role, depending on FDA acceptance.
- Regulatory pathway adjustments: Traditionally, introducing a drug-device combination product requires an original new drug application (NDA). However, the PDURS guidance appears to allow for submission of a supplemental NDA (sNDA) to modify the label of an existing drug to include software-related benefits. This could open a new regulatory pathway to enhance the efficacy of existing drugs by integrating software into the treatment experience.
- Increased value of software-as-a-medical-device: Generally, by claiming clinical benefit due to the software, the software has a medical intended use, which means it is regulated as software-as-a-medical-device (SaMD). Most SaMD products must meet the requirements of class II medical devices, including quality management systems, with application of rigorous development and on-market controls, and provision of robust clinical data to validate safety and effectiveness. Thus, software developed as SaMD, such as prescription digital therapeutics (PDTs), is well-suited to establish added clinical benefit claims under PDURS compared to digital health, commercial companion applications or digital research tools that do not meet these standards.
- Competitive differentiation: The ability to demonstrate added clinical benefits through software gives manufacturers a significant competitive advantage. Manufacturers can differentiate their brands not just through traditional means (e.g., contracting, patient support programs, distribution models) but also by showcasing enhanced efficacy and patient outcomes facilitated by their software. This truly enables manufacturers to unlock the full potential of their respective pharmacotherapy.
- Stakeholder engagement: Beyond regulatory approval, manufacturers must consider the perspectives of healthcare providers, payers, and patients. The data generated should resonate with all these stakeholders to ensure adequate reimbursement, adoption, and demand. And importantly, developing and commercializing high-quality digital experiences as part of product offerings – experiences that offer meaningful clinical benefit, backed by evidence and FDA review – can yield a new type of long-term, persistent digital relationship between the manufacturer and patients and providers.
Demonstrating Meaningful Clinical Benefits
To leverage PDURS effectively, manufacturers first need a deep understanding of current treatment gaps and TA-specific unmet needs for brands to guide them towards the largest opportunities. After that, they can leverage and customize digital therapeutics to address key customer and patient challenges with side-effect monitoring, dose optimization, and behavioral health support. Manufacturers have historically been limited in solutions, and digital interventions activate a new channel of innovation to enhance the value of pharmacotherapies. From a regulatory perspective, they should focus on generating robust clinical evidence by designing and conducting rigorous studies that adhere to GCPs and include control conditions to establish the efficacy of the software in conjunction with the drug. Engaging with the FDA through regular meetings with the agency’s review divisions can help manufacturers align their study designs with regulatory expectations. Additionally, real-world evidence can supplement these findings and provide additional insights into the software’s benefits over time.
Commercial Benefits of PDURS
The PDURS guidance opens several opportunities and supports future commercial success for manufacturers. By enhancing existing clinical benefits through their software, manufacturers can further stand out in competitive therapeutic areas. But most importantly, this combination pathway supports further innovation and eases historical access and commercial struggles for software-only therapies by enabling reimbursement of both the software and drug through the traditional pharmacy benefit model of existing pharmacotherapies (an important topic our firm will address further at a later date). Ultimately, this guidance arms manufacturers with future opportunities for FDA-label enhancement. This will be a key resource to build value-perception and support future stakeholder discussions with U.S. payers and HCPs for enhanced access and adoption. Finally, as legacy brands continue to mature and face non-branded competition, the combination of integrated software can help maintain demand by offering unique robust clinical benefits that generic competitors can’t replicate.
Strategic Adjustments for Manufacturers
This guidance, while still early, demonstrates the FDA’s recognition of therapeutic synergy between software and traditional pharmacotherapy by providing a novel tool for brand strategy planning. Therefore, to capitalize on the PDURS guidance, manufacturers should:
- Identify current & future gaps: Conduct internal in-line and pipeline assessments to identify priority therapeutic unmet needs that may be supported by non-pharmacotherapy intervention
- Invest in digital innovations: Develop sophisticated, personalized software that can enhance clinical patient outcomes and differentiate their products
- Build long-term relationships: Leverage digital therapeutics to engage patients continuously, gathering real-world data that can inform future drug claims and market strategies
- Plan for data integration: Ensure that clinical and real-world data are collected, analyzed, and utilized to strengthen the drug’s value proposition across all stakeholders
By understanding and preparing for this new regulation, manufacturers can innovate and thrive in the evolving healthcare landscape. Above all, manufacturers should start planning now to stay ahead of the competition and harness its full potential.
To learn more about The Dedham Group’s digital health consulting practice and how we can help guide you to success, contact us. To learn more about product development collaboration under PDURS pathway, contact Click Therapeutics.
