The FDA (Food and Drug Administration) has authority over products intended for the diagnosis, treatment, or mitigation of human disease. They're regulated, and the FDA has the authority to pull products to ensure human safety and efficacy.

Eteplirsen

Recall from Week 7 - Bioinformatics#Rapid Testing for COVID-19 & DMD that exon-skippin is an approach to treating DMD. The drug eteplirsen masks the exon that contains a mutation that causes the dystrophy gene to fail. The exon is then skipped during transcription and thus the mRNA that leaves the nucleus is shorter, but functional.

The early trials were concluded by the FDA to not work for a larger trial. However, some parent still wanted to try the treatment, so a "fast track" method was implemented to speed the approval process for patients with dire needs.

Eteplirsen was granted approval for this in 2016, and more clinical studies are occurring until 2020 (and more on other drugs have come out over the years). But let's look at the normal approval process for drugs.

FDA Approval Process for Drugs

You can see:

for more details.

Stem Cell Therapies

Some stem cell therapies have been discussed; however, there are very few uses for them to date. The FDA has no ability to regulate procedures which take stem cells from a persons body, isolate them, and then re-inject these stem cells back into the body in a different location. Scientists and physicians agree that these unregulated stem cell therapies are ineffective and often harmful.

A Great Idea!

How do you get rich off of your medical device/app idea? Let's look at an example; SleepCycle. It's an app that uses the microphone and accelerometer app to monitor a persons' sleep, and serves as an alarm clock that only uses light to wake the user at precisely the right time.

Is SleepCycle a Medical Device: YES or NO?

It is not a device. The developers of it cleverly marketed the device:

• They made no claims that it would actually make you more refreshed
• They restate findings of other studies to suggest, but not implicate, the app's usefulness
• The FDA defines a device as: "Any article or health care product intended for use in the diagnosis of disease or other condition or for use in the care, treatment, or prevention of disease that does not achieve any of its primary intended purposes by chemical action or by being metabolized." Since the product in question doesn't diagnose, treat, or prevent a disease, it's not a medical device.

Instead, they are considered a home health product. Examples include:

• Calorie counters
• Stop smoking apps
• Help with pychiatric disorders
• Information about drug/supplement interactions
• Asthma warnings based on location
• Symptom screening linked with potential diagnoses

Types of Medical Products

Classification of a product as a drug, biologic, medical device or combination product depends primarily on that product's intended use and principal mode of action:

• Biologics: derived from living sources. Different from most drugs which are chemically synthesized and have known structure. Examples are: human blood, plasma.
• Medical Devices: any article or health care product intended for diagnosis, treatment, or prevention of disease without any chemical action.
  • Class I device - Non-life sustaining, failure poses no risk to life, and no need for performance standards
  • Class II device - non-life sustaining, but must meet some performance standard
  • Class III device - sustains or supports life, failure is life-threatening
• Software is also regulated
  • Class I - subject to general controls relating to misbranding, registration, record keeping, etc.
  • Class II - general control are insufficient to ensure safety and effectiveness, performance standards help to provide assurance
  • Class III - generally considered life-sustaining, possibly implanted in the body.

Approval Process

The FDA want to protect US citizens from harm. The approval process for medical devices is very similar to that for drugs:

• preclinical research
• clinical trials
• manufacturing practices
• marketing materials

Let's look at a few more details of the process:

• Some products can avoid full review:
  • Exempt status - certain well-defined categories of class I and a small number of class II products are eligible for a request for exemption from the normal approval process.
  • Pre-market notification or 510k clearance allows a manufacturer to market a product which is substantially similar to other approved class II products. Not available to class III products.
• Other products posing a significant risk must undergo the Premarket Approval (PMA) process. Required for class III devices
  1. Non-clinical tests - document safety and effectiveness of device before being used on humans. Can include bench tests, simulations, or animal studies
  2. Investigational Device Exemption (IDE) - Non-clinical testing is submitted to FDA to request an IDE which allows investigators to begin clinical testing on human subjects. The device is only allowed to be used in the studies described in the IDE application.
  3. Clinical Trials - Even with an FDA approved IDE, clinical trials must be approved and monitored by an Institutional Review Board (IRB). Trials are conducted in phases:
     • Phase 1: Healthy subjects tested to look for harmful side effects
     • Phase 2: Small sample of diseased patients to determine proper dosing or procedures
     • Phase 3: Large sample to determine efficacy and potential risks

FDA requirements for clinical studies include:

• written investigator agreement
• investigator training
• approval by IRB
• informed consent
• ...

When all studies are complete, they are submitted to the FDA for PMA, then the marketer can market and sell their product to the public.