How the FDA regulates pharmaceutical apps

By MHN Staff
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Bradley Merrill ThompsonBy Bradley Merrill Thompson

Mobile apps seem all the rage in the pharmaceutical industry.  According to the website InPharm, there are presently over 100 of them publicly available. Based on what I'm hearing from pharmaceutical companies directly, that's only a small number compared to the apps in development.

Recently there's been a debate going on in the UK about whether pharmaceutical apps are medical devices under EU law. Consulting firms Bluelight & d4 suggested in a January report that many health-related apps are indeed medical devices in the UK. Specific to pharmaceutical apps, the report suggests that at least in the UK "if your app will be associated with, contributes to or makes a clinical decision, assume that it will be classified as a medical device…." The report stirred quite a controversy among champions of innovation and free speech.

In the US, there've been a couple of events recently that have caused pharmaceutical companies to focus on these issues. First, FDA held a public hearing in March to take testimony on whether greater reliance on patient decision support software could allow certain drugs to be switched from prescription status to over-the-counter. That prompted companies to wonder how such software would be regulated. Further, on May 18, in an issue briefing for congressional staff, Dr. Jeff Shuren, the director of the center at FDA that regulates devices, spoke plainly about the agency's intention to deregulate certain apps used for low-risk pharmaceutical management.

In my series of posts on this website 2 years ago, I laid out the basics of FDA regulation of mHealth. Now I'd like to expand that to address FDA regulation of pharmaceutical apps.

iPhone_FDARegulatory Categories

The starting point is to understand the four different possible regulatory categories into which pharmaceutical apps might fit. Those four categories are:

1. Heaven on Earth, a.k.a. Apps not Actively Regulated by FDA.  Just about everyone wants their app to be unregulated. And Utopia it nearly is. But, not to be a Debbie Downer, I need to be clear this just means unregulated by FDA (and even that status may change in the future).  Most apps would still be regulated by the Federal Trade Commission, and indeed it was FTC that brought one of the first enforcement actions against a mobile app developer. Further, nearly all apps would be subject to state regulators, Lanham Act challenges by competitors, and tort law if they hurt somebody.  So it's probably still a good idea if app developers exempt from FDA regulation nonetheless test their apps to make sure they work.

2. Drug labeling. FDA law makes it clear that information provided by a pharmaceutical company in support of its drugs qualifies as a regulated drug labeling even if it is not physically near the drug itself. Generally there are two kinds of labeling:

  • Prescribing information—also sometimes referred to as product labeling or a package insert—provides carefully crafted information regarding instructions for use.  This information is highly regulated and, for new prescription drugs, is the subject of much negotiation between the manufacturer and the agency.
  • Promotional labeling—is used to help sell the drug. This kind of labeling comes in all different shapes and sizes from brochures and booklets, videotapes, refrigerator magnets, cups and other giveaways to virtually anything else where a pharmaceutical company tries to convey a message about its drugs.  There are different levels of promotional labeling; for example, a reminder advertisement is intended merely to convey the brand name.

A full discussion of the contours and scope of promotional labeling is well beyond this post, but suffice it to say that apps and other software used to convey information about a prescription drug will typically be regulated at least as drug labeling. As such, the labeling must include (at a minimum) full prescribing information, and perhaps need to be filed with FDA at time of first use.

3. Medical device. Yes, I said a medical device. In my previous posts, I explained the medical device definition ad nauseum, and I don't want to bore you with the details of that again. Basically software, if intended for a medical purpose in the treatment or diagnosis of disease, can be a medical device.  In the guidance document FDA published last summer on mobile medical apps (MMA), FDA outlined its thinking on when mobile medical apps would constitute a medical device. A specific category mentioned in that guidance is standalone clinical decision support (CDS) software, or software that is not connected to any medical device but provides information used in the treatment or diagnosis of disease. The agency explained that it was beginning a process to refine its definition of the scope of regulated CDS, and then they held a public workshop on the topic in September of 2011. At that workshop, FDA suggested that there were three primary elements to CDS, including:

  1. Data taken from any source, for example, a medical device, environmental data or demographic data;
  2. A conversion, by which the FDA seemed to be referring to the use of algorithms, formulas, database lookups or other analytic steps to produce;
  3. An actionable result, which I understood to have two key defining characteristics: (i) a specific patient and (ii) a specific recommendation, not a list of possibilities.

The agency then gave some examples of what they would consider CDS, and offered up BMI calculators, trending algorithms, medication reminders and drug/drug interaction software to be examples of low-risk CDS. On the high-risk side, the agency mentioned radiation dose calculators, medical imaging analyzers, cancer treatment software and complex analyzers for untrained users.

The agency is working on a CDS guidance, but in the MMA guidance the agency made it clear that it does not plan to regulate:

  • Electronic copies of medical textbooks;
  • Apps that are simply used to provide clinicians with training;
  • Apps that are used for general health and wellness, and not disease; or
  • The traditional electronic health record apps used as an electronic health record.

FDA also indicated that they would use enforcement discretion to hold back on regulating certain apps they consider to be medical devices, but that are low-risk. The draft guidance wasn't very specific, and hopefully the final guidance will elaborate more, but in a footnote (#13) FDA mentioned apps “that may meet the definition of a medical device [and] have functionality either to automate common medical knowledge available in the medical literature or to allow individuals to self-manage their disease or condition.” Remember, always read the footnotes!

As I mentioned above, on May 18, 2012 Dr. Shuren spoke at a Capitol Hill briefing where he revealed a little bit of the agency’s thinking. He explained that the items listed above are low-risk CDS and would likely not be actively regulated. Putting the pieces together, it would seem that although FDA might say that they qualify as medical devices, they plan to exercise enforcement discretion and not regulate them presently. Dr. Shuren specifically mentioned not regulating:

  • Educational tools (e.g., apps that provide a list of questions to ask physicians);
  • Medication reminders for therapy adherence;
  • Simple, common calculators (e.g., for tabulating an apgar score);
  • BMI calculators;
  • Drug-drug interaction formulae;
  • Diabetes management guides (e.g., nutritional guides or pre-diabetes risk assessments); and
  • Substance abuse behavior guides.

Because it was part of an informal panel discussion, we don't have much detail on specifically the scope of each of those categories.

4. Combination products.  This category only applies if the app first is a medical device. If that's true and the app cross-references a drug to be used with the app, and if likewise the drug cross-references the app to be used together, that creates what is called a combination product. Below I'll give some examples of combination products, but for the moment it’s simply important to understand that if an app and a drug together constitute a combination product, it means the FDA regulatory process gets a bit more complex. Literally it means that two different centers at FDA—the drug people and the device people—get actively involved in regulating the product. FDA has put in place some procedures for improving the coordination of the reviews between those two centers, but it is not without its challenges.

Okay, that's the background. Now let’s get to the interesting stuff: the apps.  The easiest way to organize this part of the discussion is to divide the apps between those for professionals and those for patients.