Medical Device Registration and Clearance is NOT the same as Approval
TASA ID: 4338
Introduction
Since 1976, the FDA has classified devices as low (1), medium (2) and high (3) risk. This article goes into detail about what medical device manufacturers are required to do to sell their products in the USA. I've been working on a case as an expert witness for a very experienced attorney. Our discussions made me realize that many of us are unaware of the details that separate a device tested in humans before being put on the market, from the vast majority of devices that are tested in the laboratory only and then sold. Let's go to a brief overview and then I will explain how to investigate potential problems with devices - what information is publicly available and what is internal to the manufacturer of the device. If you represent a plaintiff that is a patient, that internal information is discoverable. If you represent a defendant such as a manufacturer or a health care facility, that internal information should be checked for compliance to the FDA's regulations and correlated to public data.
Background
Only class 3 medical devices require clinical trials and post market reporting, similar to the way new drugs are approved. There are class 2 devices that require post-market surveillance1 but they do not have the pre-market human trials requirement of class 3. Class 2 devices represent the largest share of new devices coming to market each year2 - for example, in fiscal year 2013, the FDA cleared 2,895 class 2 devices and approved 44 class 3 devices.
Class 1 devices are for the most part exempt from quality systems regulations but still need to be manufactured according to current Good Manufacturing Practice (cGMP) and the manufacturer must list and register all devices manufactured in the USA or in foreign countries.3 Manufacturers and initial importers/distributors also must keep a complaint system for class 1 devices.
Back in 1976 when the current classification system started, the FDA grandfathered in devices that were on the market, and if a manufacturer of an existing device made modifications due to advancements in technology or cost savings, the idea for a class 2 device (moderate risk) was to prove “substantial equivalence” to the current device. The practical implementation of this idea was and is the FDA’s “510(k)” application4 to inform the FDA of intent to market a device. A 510(k) application has sections applicable to biocompatibility and safety testing, software testing (if applicable) and bench testing for physical performance features, but there is no requirement for clinical (human) testing. So the tests are carried out by manufacturers using cell culture in a test tube or petri dish (in vitro), in animals (in vivo), to physical standards for performance, and simulations to test software. The tests can be performed in house if the manufacturer has the resources, or most commonly at independent research labs. The lab will produce a report making reference to the standards and protocols used in running the test, and the manufacturer will include the report in the 510(k) application. When the FDA accepts all the manufacturer’s claims in the 510(k) application after review and discussion by the FDA’s device division, the the FDA issues a letter stating the device is now “cleared” to market.
Class 3 devices are “approved” by the FDA after a process that includes a premarket application (PMA) including clinical trial data and specific post-market reporting requirements. I have not myself worked on PMA device filings because the costs to bring such devices to market are high and out of reach for smaller manufacturers. Most PMA devices come from larger companies or spinoff ventures of a research institution.
Investigating Problems
The regulatory environment means it’s up to manufacturers to estimate risk and identify hazards in their devices. Manufacturers must continue to monitor their devices for adverse events once the devices are sold and used on patients. The FDA has limited resources (the “F” stands for “Food”) and their many field offices and regional labs are quite busy with food producer inspections. The FDA is charged with protecting patients and has the power to initiate recalls of unsafe devices5 but often the media reports stories of unsafe devices before the FDA is made aware. My intent is not to bash the FDA because the people I know who work there are swamped. It’s being realistic to say that the regulators cannot be everywhere and see everything.
There is no universal standard for assigning risk to a medical device, and competing manufacturers of devices may quantify risk differently for similar identified hazards. One manufacturer may identify a hazard as a high enough risk to warrant triggering an alarm, and their competitor may decide that same hazard is not such a high risk and just note it as a “feature” for the label.
If a patient experiences an adverse event and the medical device is suspected to have caused or contributed to the problem, the FDA medical device reporting (MDR) comes into effect6 and that data is put onto a public searchable database called MAUDE. MAUDE data can be searched by product code, manufacturer, dates, regulation sections and geography. It’s fast and free, but the data is not perfect. It’s up to manufacturers and clinical sites to report the data, which can be underreported, missing, incorrect and subjective. However, all clinical sites are supposed to file reports within 10 days of the event, and manufacturers must file within 30 days of the event. The FDA can also request a 5 day report of the manufacturer if it suspects there is a severe problem with the device. MAUDE also has a section link in each search called total product life cycle (TPLC) where recall information is available for devices. It can be useful to compare for each product code – it shows which manufacturer or the FDA has initiated recalls for that type of device.
The FDA warning letters and 483 citations are available as a follow on search of public, free data for device problems. The FDA warning letters7 and 483s8 are originated by trained inspectors and reviewers at the FDA and show detail of what the FDA thinks is a problem with the manufacturer’s compliance or deviation to quality systems regulations.
If public information shows a trend then the manufacturer’s own internal documents should reflect awareness of the situation with their medical device and what is being done to correct the problem. Manufacturers must keep complaint files no matter the class of device. Also all manufacturers must have documented good manufacturing practices (cGMP) and correct labeling of the device. The FDA considers a device to consist of: 1. The physical device itself; 2. Packaging; 3. Labeling; 4. Instructions for use; and 5. Applicable quality systems regulations. The FDA considers a device adulterated if it is not in compliance with any of these areas and can consider the device as being illegally marketed in the USA.
Internal documents must be reviewed by manufacturers when taking corrective action/preventive action (CAPA) to reduce risk to an acceptable level. Most applicable are the device’s complaint file, risk file, device history file, and medical device reporting file. All medical device manufacturers should regularly review these files and compare the information to what is public data on the the FDA web site. It can be a big problem if deaths or severe injuries are reported on the FDA’s site and the manufacturer has incomplete information on the event.
Endnotes
This article discusses issues of general interest and does not give any specific legal or business advice pertaining to any specific circumstances. Before acting upon any of its information, you should obtain appropriate advice from a lawyer or other qualified professional.
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