Regulatory Pathways for Medical Devices

A Case Study

Moshe Ben Yitzhak, MBA, MScGGMP Solutions

IntroductionA small start-up company, lead by a pediatrician with 35 years of experience, is entering the medical device field. The doctor is convinced that he can design certain medical devices that are more user-friendly. In order to attract investors, he has recruited a small team to develop the business plan. His first two employees are the Regulatory Affairs (RA) Manager and Engineering Manager. He has tasked the RA Manager with learning as much as possible about the FDA and the regulation of medical devices. He has given the Engineering Manager the task of designing a prototype.

The Presentation• The RA Manager started the presentation.• She opened her computer to the FDA’s home page, and then clicked on the

Medical Devices tab.

The Presentation

Scrolling down, she indicated a number of areas in

which the FDA

offered free

advice to start-ups

that qualified for help.

She pointed out that if the device would be distributed in the U.S.,

the firm would have to be registered with the FDA.

The fee the FDA charged for registering an establishment changed yearly, and would have to included in the company’s upcoming budget.

Under the “Tools & Resources” section, there is a database of devices that have been submitted to the FDA.

These databases, she explained, were updated at different frequencies. They could be searched, and would help the start-up refine and differentiate the device from similar products.

She typed in the words “infusion pump,” to demonstrate, and selected

“Infusion pump management unit, mobile.”

The search returned an impressive list of results! Too many to sort through one-by-one. However, users could also filter and sort the results to match certain criteria.

Global Unique Device Identification Database

• This table gives you four types of information: the device name, the three-letter product code, the device class, and the regulation number.

– Device name is the general name, like blood pressure cuff.

– Device class shows which risk category a type of device falls into and the controls that are necessary to mitigate the risks to health.

• Class I, and a device like a heart-lung bypass machine would be Class III, because problems with one of those could be serious.

• Class II, for devices that are moderate risk.

– The regulation number shows the part of the Code of Federal Regulations that identifies that type of device and establishes the class.

Finding Problems before R&D Starts

“The device I want to introduce is an infusion pump that is not implanted in the patient,” said the doctor, “therefore it would probably be a Class II device.”

“That’s right,” said the RA manager.

“But we also want to learn what problems other companies have had, so we can avoid them” the Engineering manager said.

“The FDA has databases for that too,” she replied.

There are three different databases that companies can search to understand what problems others have encountered.

Finding Problems before R&D Starts• After researching infusion pumps

in the FDA databases, the Engineering manager and the doctor met.

• The doctor began. “We have the formula on the drug release rate, and we’ve nailed down the critical attributes and parameters.

– How are we going to design the method of delivery—electronically or mechanically?

– Have you learned enough to know which technology has a better chance of standing up to regulatory scrutiny and succeeding in the marketplace?”

Finding Problems before R&D Starts

“I love my smart phone,” the Engineering manager started. “I use it to organize my life, find information, and play games and videos. But unlike a lot of my friends, I still have a landline.

Why? My smart phone demands constant program updates and upgrades to fix bugs and improve functionality, and every once in a while, it freezes. Not my landline. It does just one thing, but it does it well and consistently and cheaply. That’s what your device would work best in a mechanical, fully disposable for.”

The doctor considered this and said, “Let’s look at mechanical infusion devices that are similar to my device. Those CDRH databases will make it easy to figure out what’s already on the market.”

The Path to MarketAt the next meeting, the team reviewed where they were. The Engineering manager had a prototype ready, and they were there to discuss the next step.

The RA manager cautioned, “Before we can sell the device in the U.S., we have to obtain either approval or clearance from CDRH. If we can prove the device is novel or if it is high risk, we can seek premarket approval, or PMA. That would allow the product to be legally marketed in the U.S.”

“Let’s get started on a PMA!” said the doctor.

She shook her head. “PMA is for high-risk devices, Class III. It usually requires clinical trials to gather data demonstrating safety and efficacy, which involves more time and investment. And to use a device in a trial, you may have to submit another application, for an Investigational Device Exemption, or IDE. The whole process could take years, and you need to have a realistic business plan.”

The doctor looked out his office window, and finally said “You’re right, it would be long and costly. That could spook investors.”

The Path to Market

The Path to MarketThe Engineering manager spoke next.

“Remember, we think this pump is a Class II device, which puts us on a different path. Now, we’ve already sized up our competition and we may be able to cite a competing product as a predicate device. So, let’s start by:

• Finding a similar legally marketed device that we can use as the predicate and document that the intended uses of the products are the same.

• Then, we’ll demonstrate that even if there are technological differences between the two devices, these differences don’t raise new questions of safety and effectiveness.

• We’ll also need to provide sufficient performance data to demonstrate that your device is at least as safe and effective as the predicate.

“This pathway is called premarket notification, or 510(k).” He continued, “And if all goes well, or if we submit a 510(k) application but FDA finds that the device is not substantially equivalent, there’s still another path: the de novoprocess.”

The Path to Market

Suddenly alarmed, the doctor interrupted, “you said data. What kind of data?”

The engineer was ready. “Class II devices are subject to regulations that the FDA calls general controls and special controls. That means:

• We’ll have to follow the Quality System Regulation, also known as Current Good Manufacturing Practices, cGMPs.

• It’s all about quality assurance—making sure the product’s design, packaging, labeling, and manufacturing meet certain standards, and the data provided for evaluation are sound.

• We’ll need to apply statistics to product development activities, things like verification testing and process validation.”

The Path to Market

“We’ll need to apply statistics to product development activities, things like verification testing and process validation.”

The Path to Market

Sensing that his managers were on top of things, the doctor asked, “What else do we need to put in our business plan? We need to show that we are looking forward.”

The RA manager jumped in. “There are a lot of things to do, but many of them can be done at the same time.

– We’ll identify the relevant regulations, standards, & guidance docs.

– While we are preparing for the submission process and planning the studies, we could seek advice from FDA through the Pre-Submission process.

– Once we get clearance for marketing, we’ll need to register and list the device with the FDA.

– And we’ll need to be sure that post-market surveillance controls are in place, which includes tracking of adverse events.

Then, we go to market with the device!”

Resources

Design Controlhttps://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm070627.htm

Overview of Regulatory Requirements: Medical Deviceshttp://fda.yorkcast.com/webcast/Play/040308365ec8405bad39b06de8561bdc1d

The 510(k) Program http://fda.yorkcast.com/webcast/Play/f59814465f674e59a19f3b61c6880ea81d

The Investigational Device Exemption (IDE) http://fda.yorkcast.com/webcast/Play/8553ad7df9054febb5ef0048e359ad1e1d

http://fda.yorkcast.com/webcast/Play/46344ca5abbb465e88404a92eed542f71d

Quality System Regulationshttps://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=820&showFR=1