by Bill Sutton (November, 2011)
Hello. My name is Bill Sutton, and I am Deputy Director of the Division of Industry and Consumer Education (DICE) and FDA's Center for Devices and Radiological Health. Welcome to CDRH Learn, FDA's web page for industry education. CDRH Learn is our latest innovative educational tool. It consists of a series of training modules describing many aspects of medical device and radiological health regulation, covering both pre-market and post-market issues. This tool is intended to provide the medical device and the radiological health industry with an information resource that is comprehensive, interactive, and easily accessible. This module is intended to provide an overview of the regulatory requirements for medical devices or what is sometimes referred to as Devices 101.
The US Food and Drug Administration (FDA) is responsible for regulating and supervising the safety of foods, dietary supplements, drugs, vaccine, biological medical products, blood products, medical devices, radiation-emitting products, veterinary products, and cosmetics. Within FDA, the Center for Devices and Radiological Health (CDRH) is responsible for ensuring the safety and effectiveness of medical devices and eliminating unnecessary exposure to radiation-emitting products.
Now, let's take a closer look at the organization chart for the Center for Devices and Radiological Health. At the top of the organization chart is the Office of the Center Director and includes the CDRH Ombudsman, followed by seven offices. Each office serves a function that collectively ensures that all medical devices placed on the market in the United States are deemed reasonably safe and effective throughout the total product life cycle.
Let's begin by looking at the Office of Compliance. This is the office responsible for ensuring that all medical devices, once placed on the market, remain safe and effective. This is the office that reviews the establishment inspection reports and recalls.
The next office, the Office of Communication, Education, and Radiation Programs, is the office that's responsible for the education of the staff, through our Staff College. This is where our Radiation Program is administered. This is where the Industry Assistant's Office is located, as well as the television studio where I'm taping this program today.
The next office, the Office of Device Evaluation, is responsible for all the pre-market reviews of applications, the pre-market notifications 510(k)s, the pre-market approval PMAs, as well as the investigational device exemptions.
The next office, the Office of In Vitro Diagnostic Device Evaluation and Safety, is the office that reviews all the pre-market applications for in vitro diagnostics, as well as all the post-marketing activities associated with in vitro diagnostics. The next office, the Office of Management Operations, is the office that is responsible for our building, our budget, general administrative requirements at the Center for Devices and Radiological Health.
Next, the Office of Science and Engineering Laboratories is where our Center's laboratories are located. They do independent lab testing, work with standards organizations, universities, and other academia.
Next, the Office of Surveillance and Biometrics is the office that's responsible for the post-marketing activities or adverse event reports with regard to medical devices.
"Who We Are" –
The Center for Devices and Radiological Health is a team of dedicated and highly skilled employees with a variety of backgrounds. Many are scientists, biologists, chemists. This slide provides an example of the type of backgrounds that are working collectively to review these medical devices. The CDRH mission is to assure that all medical devices, once placed on the market, are reasonably safe and effective. We do this by looking at the benefit/risk, when we review these medical device applications. Once a device has been found reasonably safe and effective, our job is to ensure that once they are placed on the market, they remain safe and effective.
And finally, we get this information to our stakeholders through our web site and through electronic notifications on how we make these determinations of safety and effectiveness.
Let's look at the definition of a medical device. It can be found in Section 201(h) of the Federal Food, Drug, and Cosmetic Act. It's a very broad definition. It basically says a medical device is “any instrument, machine, contrivance, implant, in vitro reagent that's intended to treat, cure, prevent, mitigate, diagnose disease in man”. Some examples could be a simple tongue depressor, or a thermometer, all the way to an advanced robotic surgical device. The definition also goes on to say that a medical device does not achieve its primary intended use through a chemical activation on or within the skin, and it's not required to be metabolized to achieve that primary intended use. If it's one of those two, the FDA would regulate that product as a drug.
This slide gives some examples of the products we regulate at the Center for Devices and Radiological Health: anything from MRI equipment, to stethoscopes, adhesive bandages, and latex gloves.
FDA was given the authority to begin regulating all medical devices on May 28, 1976. This is when the President signed the Medical Device Amendments Act. FDA interprets the law that was written. We write proposed rules. We put those proposed rules in the Federal Register. Think of the Federal Register as the US government's daily newspaper. We ask for comments. We consider those comments. We then write a final rule. That final rule is posted in the Federal Register. Once those rules go final, they're placed in the Code of Federal Regulations, Title 21, Parts 800-1299.
So, I always like to say that it's the medical device amendments that give FDA authority to regulate medical devices. It's the regulations in 21CFR, Parts 800-1299, that give FDA and industry guidance on how to comply with the provisions of the Act.
This slide describes the device classification. FDA has classified all medical devices into either Class I, II, and III. Currently, in the Code of Federal Regulations, there are about 1700 devices that have been classified by the FDA. They can be found in 16 medical specialties or device panels.
Here's an example: Anything that begins with Part 870 is a cardiovascular device. Anything that begins with Part 880 is general hospital, and so on.
Here's an example of a regulation and how product codes play a part in the regulation classification of a medical device: If you were to look under Part 880.5780, you would see a short identification for a medical support stocking. Now, look closely at the identification. A medical support stocking that is intended to prevent the pooling of blood in the leg is a Class II medical device and requires a pre-market notification. FDA will assign a distinct product code, DWL, for these types of devices.
If you are intending to label that medical support stocking for general medical purposes, it's now Class I, and it's exempt from pre-market notification 510(k). The product code FLL is unique for the Class I exempt medical support stockings.
So it’s very important to look online at our product classification database. Look at those regulation numbers. Look at those product codes to ensure that you have identified the most appropriate regulation product code for your device. I said earlier that FDA has classified about 1700 device types. Let's look at how these are broken out by class.
Class I devices are the low-risk devices.
There are about 780 of those. They require general controls, and I'll talk about those general controls next.
Class II devices require general controls and special controls.
There are about 800 Class II medical devices. These are our medium to moderate risk devices.
Finally, Class III require general controls and pre-market approval, PMA.
Those are the lower number of classified devices, about 120; however, these are high risk, generally life-supporting, life-sustaining devices.
So, let's look at those general controls that apply to all classes of devices,
Class I, Class II, Class III.
The law is very clear in that no medical device shall be adulterated or misbranded. Those are the two violations that the Office of Compliance will issue a letter for to medical device firms. An example of adulteration would be manufacturing a device that is not in compliance with our quality system regulation, our current good manufacturing practices. Adulteration could be placing a device on the market that requires a marketing application such as a 510(k), but the firm failed to get that 510(k) clearance.
Misbranding, that could be putting an intended use on a device labeling that FDA did not clear that device for. It could also be selling a device over the counter that requires a prescription labeling. That's misbranding, and that's prohibited under the federal Food, Drug and Cosmetic Act.
Next, electronic establishment registration.
I'll talk more about that. This is a requirement for all finished device manufacturers, as well as importers of medical devices. Manufacturers must also list their medical devices with the FDA at the time they plan to market their device.
General controls may be a pre-market notification or 510(k), and I'll talk more about the 510(k) program. General controls require that all finished device manufacturers comply with our quality system regulations, our current good manufacturing practices. General controls require that all medical devices be properly labeled.
Also, general controls require that all manufacturers, user facilities, and importers report when there's been an adverse event with a medical device. This is known as our Medical Device Reporting program or MDR.
Now, let's look at those special controls for those Class II medical devices. A special control could be a guideline. Here's an example of a glove manual: This glove manual will give the manufacturers specific information about how to prepare a 510(k) application for a medical glove. A special control could be a mandatory performance standard. Today, FDA has only written one mandatory performance standard,
and that's for patient cables and electro lead wires. However, the FDA has been able to recognize over 800 voluntary standards. These could be other recommendations or actions.
A special control could be special labeling. Here's an example (on this slide) for special labeling for a cranial orthosis. There's special labeling for IVDs, for hearing aids, for condoms. So, very important to look to see are there special labeling requirements for your medical device?
And, finally, a special control could be a guidance document.
FDA has written many guidance documents, not a guidance for every medical device application. The FDA Good Guidance Practices Database provides a listing of all those guidance documents, and FDA encourages you, the manufacturer, to look for those guidance documents to assure that you're going to meet the requirements that we would expect to see in those medical device applications.
I talked earlier about a general control being Establishment Registration and Medical Device Listing. This is a good point to make, that FDA requires the finished device manufacturers to be the ones that register to list and submit those medical device applications. This is done now electronically. It's done after the manufacturer has received their 510(k) or PMA clearance, or at least within 30 days of going to market with their medical device.
And yes, firms outside the United States must also register and list, as well as name a US agent for that foreign establishment. The US agent must reside in the United States, must be familiar with the operations of that foreign establishment, and FDA may contact that US agent if we need to get information to the foreign manufacturer. At the same time a manufacturer registers their establishment, they also want to list their medical devices. This let’s FDA know where the medical device is being manufactured and what type of device is being manufactured, so that that manufacturer can be found for an inspection later by the FDA field offices.
Annual registration is done every October through December for the upcoming calendar year.
Another general control that I talked about is the pre-market notification or 510(k) program. I only have a couple of slides to talk about the 510(k) program. This is a general overview. This is something that we could talk probably a couple of days about, but it's important to know that a 510(k) is a marketing clearance process. It is not an approval; again, it’s a marketing clearance process. There is no form. However, there is a format on content and format. There's guidance online that will assist the applicant on preparing that 510(k) application.
The 510(k) must be submitted at least 90 days prior to market.
The purpose of a 510(k) is to demonstrate that one device is substantially equivalent to another legally-marketed device. This could be a device that was on the market prior to 1976 or has since been found equivalent through the 510(k) program.
So, what does substantially equivalent mean?
It means it's just as safe and it's just as effective as the predicate device. Again, not an approval; it's a clearance, and FDA is determining Substantial Equivalence.
So, when is a 510(k) required?
When an applicant is planning to introduce a device on the market for the first time under their name or if they made significant modifications to their currently marketed device and those modifications may have significant effects to safety and effectiveness that would require a new 510(k). The good news is that we do have a guidance document on helping manufacturers determine when a modification may or may not require a new 510(k). Now, some medical devices are exempt from 510(k), so general controls is a 510(k) unless exempted by statute.
In 1997, through the passage of the FDA and Modernization Act,
Congress authorized the FDA to exempt all Class I medical devices, remember, those low-risk medical devices. FDA was not comfortable with exempting all Class I devices, and there are still about 50 device types that require a 510(k). We refer to those as Reserve Devices, but there are about 93% of those Class I devices that are exempt, or about 730 devices.
Congress also gave FDA authority to begin regulating some Class II medical devices. There's about 9% or 70 of those Class II devices that are exempt from 510(k).
You don't have to guess if you're exempt. Again, the regulation in the Code of Federal Regulations will identify or state whether the device requires a 510(k) or if it's exempt from 510(k).
We do have a Third Party Program that was mandated through the passage of the 1997 FDA and Modernization Act. We currently have third parties both in the United States and outside the United States that can review 510(k)s on our behalf. They make recommendations and submit those recommendations and the 510(k) to the FDA for review. This is also known as our Accredited Persons program.
The special 510(k) –
I talked earlier about making modifications to a legally cleared device.
If an applicant needs to make or makes modifications that require a new 510(k), they may be eligible for a special 510(k) by submitting a Conformance to Design Controls, which is a part of our quality system regulation. FDA agrees that it meets the criteria for a special 510(k). We're committed to reviewing that within 30 days.
And, finally, the abbreviated 510(k) is where the applicant is complying to a recognized standard, a guidance document; and, hopefully, with the reduced data that's going to be provided in that 510(k) and by the reviewer just primarily looking at the summary of that data, we may be able to review those devices quicker than 90 days.
There is a 510(k) device user fee.
This began in the year 2002. There will be a standard fee for the 510(k), as well as a small-business fee for that 510(k), and the small business fee would be looking at the applicant, including the applicant, if they have a parent firm, if they have affiliates, that their combined gross receipts and sales for the most recent tax year were 100 million or less. They can apply for that small business fee, which may reduce that fee by 50%.
Now, let's look at the Pre-Market Approval Program, or PMA.
The pre-market approval is an application required for the high-risk medical devices, those Class III medical devices I referred to earlier. A PMA is going to be required if the regulation or classification in the Code of Federal Regulations require the PMA. It could also be for a device that there is no equivalency. It's not substantially equivalent to any other device like that on the market. In other words, it's new. There's no basis for substantially equivalent. This could be because there is no predicate device labeled with the same intended use on the market, FDA's never seen that device before, or it could be that the predicate was not cleared for those intended uses.
And, again, we at the FDA have not seen that type of device before, or it could be that technology associated with that device raises new questions of safety and effectiveness that may require a PMA or pre-market approval application.
And the purpose of the PMA is to show the FDA or to demonstrate to the FDA that through valid scientific evidence, the device is reasonably safe and effective on its own. So, where the 510(k) is really a comparison or a "me too" to the predicate device, the PMA device is standing on its own, and that's primarily done through a lot of clinical studies.
Now, there is a PMA device user fee for that device review by the FDA.
Just like the 510(k), there's a standard fee, as well as a small-business fee.
The good news is that for that PMA device, if it's the very first PMA application for that applicant and the applicant is able to demonstrate that their most recent gross receipts and sales for the most recent tax year were 30 million or less, FDA is going to waive that fee. If it's 100 million or less, there will be a reduced fee.
Now, so far, I've talked about the two types of marketing applications at the FDA: the pre-market notification 510(k), as well as the pre-market approval or PMA. FDA is also responsible for the review of all unapproved device studies, the devices and the studies themselves that are going to be used on human subjects in the United States. So, what does that exempt the applicant from? They don't submit marketing applications. They don't register/enlist with the FDA. There are a few other exemptions, as well, but again, these are regulations for unapproved medical devices.
The way that FDA looks at unapproved medical devices is we put them into one of two categories: significant-risk devices or non-significant-risk devices. Think of those significant-risk devices as those high-risk Class III devices, life-supporting, life-sustaining devices. Before the applicant or sponsor of that study can begin that study, they must obtain IDE approval from the FDA first. However, if it's deemed to be a non-significant-risk device, FDA does not need to approve that study, but what FDA does require is what we refer to as the abbreviated IDE program. That's going to require institutional review board oversight, so basically the IRB will serve as the surrogate FDA and have oversight of that study, and also there must be informed consent. So, the subjects participating in that study must know that this is an unapproved medical device. They must be made aware of the benefits, as well as the risk in participating in this study. The IDE program is intended, again, to be used on human subjects, to collect safety and effectiveness data, and most importantly, they are intended to protect those human subjects in the study.
I spoke earlier about the general controls.
That includes medical device labeling. What I'd like to say about this slide is that labeling is really anything associated with that device. It can be the labeling that's on the device. It can be instructions for use, advertising and promotional material. It's all labeling, and FDA would like to see all of that in the marketing application. Labeling must provide adequate directions for use, unless it's exempt, and what that refers to is our prescription requirements for devices.
Most medical devices placed on the market are prescription devices.
What that means is they can only be sold to or on the order of a physician, and labeling must not be false or misleading. If it is, it's misbranding; and as I talked about earlier, that is a violation of the Federal Food, Drug and Cosmetic Act. The Quality System Regulation or current good manufacturing practices is a good quality assurance program that the manufacturers must follow when marketing that device. What that does is it gives FDA assurance that once FDA has cleared that device for market, that it's going to be manufactured consistently, according to the specifications for which FDA granted marketing clearance or approval. It's very similar to the International Standard 13485, and it's the standard for which we audit and spec medical device manufacturers against.
Next, Medical Device Reporting, or MDR, is a general control.
This is our adverse event reporting program. It's a mechanism that FDA has in place for identifying, monitoring, and capturing adverse events involving medical devices. This is when a medical device may have caused or contributed to a serious injury, death, or if a malfunction was to reoccur, may cause or contribute to a serious injury or death. That must be reported to the FDA. Who needs to make those reports? Manufacturers, user facilities, and importers of medical devices.
Let's now take a look at post-market studies.
Post-market studies are a means by which FDA can collect safety and/or effectiveness data for a 510(k) cleared or PMA-approved device. The first type of post-market study is a post-approval study. A post-approval study is a study that is required as a condition of approval for a PMA. A PMA may actually have more than one post-approval study and may include both clinical and non-clinical studies. In general, a post-approval study is a clinical study intended to collect long-term safety and/or effectiveness data for the approved device or to collect data that shows the device's safety and/or effectiveness in a real-world setting.
Now, Section 522 Post-market Surveillance Studies, on the other hand, are studies that are mandated by FDA any time after a 510(k) is cleared or a PMA is approved. The criteria for a 522 study are a Class II or Class III device are –
One: for which failure of the device would be reasonably likely to have a serious adverse health consequence; Two: it's expected to have significant use in pediatric populations; Three: it's intended to be implanted in the body for more than 1 year; or Four: it's intended to be a life-supporting device used outside of the user facility. Section 522 studies are typically designed to address specific questions. After completion of a post-approval study or a Section 522 Post-market Surveillance Study, the labeling for the device is updated to reflect the findings.
Now let's look at medical device tracking, another post-marketing tool the FDA has in place to ensure the device remains safe and effective once granted marketing clearance or approval. Much like the post-market or post-market surveillance devices, medical device tracking devices are either going to be Class II or Class III-- again, the failure of which would reasonably have a serious public adverse health consequence--is implanted in the body for more than 1 year, or is life-sustaining, life-supporting, used outside of the device user facility, a hospital. Here's a couple of examples: a replacement heart valve, mechanical, or a ventilator used in the person's home is a tracked device. And the purpose of a tracked device, again, is for the manufacturers to know exactly to the end user who has that device, so that if they become aware of a problem that needs to be corrected quickly with these high-risk devices, that they can get that notification to the end user as quickly as possible.
I've gone through many of the regulatory requirements for medical devices.
This slide is intended to provide a reference for where the viewer can look for more information on these various programs. I encourage you to look at the Code of Federal Regulations online for these references to get more information.
Now, I have covered a lot of information here. It was a general overview of our device regulations. The good news is there is a mandated division where you can go and get assistance 5 days a week, Monday through Friday, 8 to 5, and that is known as the Division of Industry and Consumer Education (DICE). We help everybody. This slide provides our e-mail address. We have a toll-free number. We have a fax number. As I said earlier, there are medical device specialists from 8 to 5 to help answer your questions.
We're going to cover and help assist you with any questions you have from pre-market to post-market, importing/exporting medical devices. Again, I encourage you to e-mail us. I encourage you to call our office if you have any questions regarding any of the information that I covered during this module. And with that said, I want to thank you for watching. There's our Web site. I hope you found this module informative and helpful, and it's given you a better broad overview of how the FDA regulates medical devices. I encourage you to look at the other modules online at CDRH Learn to learn more information and go into more depth about the information that I've covered today. I thank you for watching, and have a good day.