The FDA Path of the Digital Pill

Why Digital Pills Need a Distinct FDA Path

As the convergence of pharma and digital health accelerates, the regulatory landscape has had to evolve to keep pace. Among the most complex products emerging from this evolution are digital pills – medications combined with ingestible sensors that monitor and transmit data about medication intake in real time.

Unlike traditional pharmaceuticals or standalone medical devices, FDA digital pills are often classified as combination products. They typically involve a physical drug, a sensor component, and companion software or data platforms.

This hybrid nature raises important questions: How should they be reviewed? Under what standards? And what evidence is required to show safety and effectiveness?

The U.S. Food and Drug Administration (FDA) has addressed these questions through two main regulatory pathways: 510(k) and De Novo. Each is suited to different types of digital pill technologies, depending on novelty, risk profile, and predicate availability.

Understanding these pathways is essential for innovators, clinical trial sponsors, and regulatory teams looking to bring a digital pill to market in the United States. In this guide, we’ll explore when each pathway applies, what clinical validation is expected, and how post-market oversight works.

For foundational context on how digital pills work, see: Ingestable sensors and ‘digital tablets’: what’s inside?

510(k): When Substantial Equivalence Works

The 510(k)pathway is one of the most widely used FDA approval mechanisms for medical devices. It is built on the principle of substantial equivalence: if a new device is demonstrably similar to one already on the market (a “predicate”), it may be cleared without the need for extensive new clinical trials.

For digital pills, the 510(k) pathway is only applicable under specific circumstances. Most commonly, this involves non-pharmaceutical ingestible sensors that are not chemically active and do not alter the pharmacological profile of the medication. These devices are submitted as medical devices – independent from any drug approval process.

A notable example: some ingestible event markers that simply log ingestion without delivering medication may qualify for 510(k) if a similar product exists and performance is comparable. In such cases, clinical validation may still be required – especially if data handling, signal transmission, or patient safety could be affected.

While 510(k) is generally faster and less costly than De Novo or full combination product review, it comes with limitations. It restricts innovation to incremental updates and is not suitable for entirely novel digital mechanisms or drug-device hybrids.

Regulatory teams considering this route must clearly demonstrate that their device performs “as well as” an existing solution — under the same intended use and technological characteristics.

De Novo: For First-of-a-Kind Systems

When a digital pill is so novel that no legally marketed predicate device exists, the FDA offers an alternative pathway: De Novo classification. This route is designed for first-of-a-kind medical devices with moderate risk, for which the 510(k) pathway is not appropriate.

In the world of FDA digital pills, De Novo has become the go-to route for companies launching sensor-based ingestion monitoring systems without an existing analogue on the U.S. market. One of the best-known examples is the ID-Cap™ System from etectRx, which in 2019 became the first standalone ingestible event marker to receive De Novo clearance.

Unlike 510(k), which relies on substantial equivalence, De Novo requires a full demonstration of safety and effectiveness, typically via:

• Bench and usability testing
• Software and cybersecurity validation
• Robust clinical validation in humans, especially if the device informs medical decisions

In the case of ID-Cap, the company submitted real-world data from healthy volunteer studies, demonstrating >97% accuracy in ingestion detection, as well as favorable tolerability and system usability. This cleared the path for broader clinical research and integration with digital platforms.

Importantly, once a De Novo device is approved, it establishes a new product classification that can serve as the predicate for future 510(k) submissions — effectively opening a new regulatory category.

Additional 2025 Considerations

Since October 1, 2023, the FDA requires inclusion of a Software Bill of Materials (SBOM) in all new submissions for medical cyber devices – a category that includes ingestible sensors – under §524B of the FD& C Act. This applies to both 510(k) and De Novo submissions, with the aim of improving transparency and cybersecurity readiness across the medical device ecosystem.

In parallel, the EMA Innovation Task Force in Europe is engaging with digital pill developers, but no centralized approval exists yet across the EU. U.S. De Novo precedent remains the most robust example of digital pill regulation to date.

Post-Market Surveillance

Obtaining FDA clearance – whether through 510(k) or De Novo – is only the beginning. Once a digital pill reaches the market, manufacturers enter a new phase: post-market surveillance (PMS). For these hybrid devices, ongoing safety and performance monitoring is not optional – it’s a regulatory expectation.

External Research & Sources

For those seeking to go deeper into the science, policy, and precedent behind the FDA’s regulation of digital pills, the following peer-reviewed studies and official publications offer the most reliable and current insights.

You can also explore related regulatory frameworks and digital health innovations in our dedicated How Technology Is Changing Pharma: A Complete Guide — a centralized space covering smart therapeutics, ingestible devices, and FDA-EMA alignment.