The Omnipod Insulin Management System

Published Date: 02 Nov 2017

Answer: Any establishment involved in manufacturing or distribution of a medical device intended for commercial distribution in the United States must register with the USFDA.1

According to the 21 C.F.R. Part 807, "device manufacturers, repackagers, relabelers, specification developers, and distributors of medical devices or ready to use components in commercial distribution must register their establishment."2

However, the revised Title 21 CFR, Part 807 (August 2, 2012) mentions a few additions to the list of establishments that need to be registered. According to this revision, the current list of establishments that require registration include- contract manufacturers (including contract packagers), contract sterilizers, Complaint File Establishments, Establishments Located in Foreign Trade Zones and Single-Use Device Manufacturers both in the US and operating outside US who intend to produce or commercially distribute the medical device in US3.

Why register?

Answer: Registering the establishment informs FDA the physical location of the establishment and the devices manufactured at the facility. The knowledge of the establishment’s location helps FDA to prepare and respond to public health emergencies. Registration information also helps FDA to conduct inspections and provide the establishment important information by mass-mailing.4, 5

How do you register?

Answer: Registration of the medical device establishment is a two step electronic registration process.

Step I entails payment of annual user registration fee and Step II entails completing the registration process.

The first few steps in registration are same for ‘Initial Registration’, ‘Annual Registration for firms without Registration number’ and ‘Annual Registration for firms with Registration number.’

These are:

Payment of Annual Registration Fee via Device Facility User Fee (DFUF) website and receiving the Payment Identification Number (PIN) and Payment Confirmation Number (PCN) after confirmation of payment clearance.

Submitting registration information using FDA’s Unified Registration and Listing System (FURLS)/ Device Registration and Listing Module (DRLM).

In case of an ‘Initial Registration’, one has to open a new account on FURLS and include the owner/ operator information along with official correspondent information if applicable, select DRLM and continue registration by adding information about the medical devices manufactured, processed or distributed at each facility along with their Pre-Market Submission number and details.

In case of ‘Annual Registration for firms with Registration number’ after logging into FURLS account, one has to enter DRLM and review the registration information. In case of ‘Annual Registration for firms without Registration number’ after logging into FURLS account, one has to enter DRLM and select. "Change Registration Information for a facility" and proceed.

In all the three cases viz. ‘Initial Registration’, ‘Annual Registration for firms without Registration number’ and ‘Annual Registration for firms with Registration number’ the final step of registration includes certifying that all information is correct an entering the PIN and PCN number when prompted6.

When do you register?

Answer: For an ‘Initial Registration’, the establishment has to register within 30 days of initiating any activity (like manufacturing) or introducing the medical device into commercial distribution. For establishments that export devices to US, they must register before exporting products to US and for importers; registration is must before importing the product. The device cannot be registered before premarket submission is cleared or approved7.

For Annual Registration, the registration information must be submitted each year between October 1 and December 31, even if there are no changes7.

Question 1b

What does the term "medical device listing" refer to?

Answer: Medical device listing refers to listing of medical devices with the FDA which is mandatory for most establishments that are required to register with FDA1.

Who is required to list a medical device?

Answer: Most establishments that are required to register with the FDA are also required to list their medical devices with FDA. These establishments include both US based and foreign based manufacturers, relablers, repackagers, contract manufacturers and packagers, contract sterilizers, specification developers, reprocessors, remanufacturers, establishments maintaining complain files and establishments located in foreign trade zone1.

Why list, and in what time frame do you list your device?

Answer: Listing gives information to the FDA about the devices manufactured at the facility. This knowledge helps FDA to prepare and respond to public health emergencies, to conduct inspections and send important information related to the device to the establishment or industry as a whole via mass mailing.4,5

For an ‘Initial Listing’, the establishment has to submit the listing information within 30 days of initiating any activity (like manufacturing) or introducing the medical device into commercial distribution. . The device cannot be listed before premarket submission is cleared or approved7.

The listing information can be reviewed annually between October 1 and December 317.

Why would the agency be interested in having this and medical device establishment registration information?

Answer: The agency would be interested in having the listing and the registration information to know the location of the facility and devices manufactured there. This information helps the agency to prepare itself for any emergency situations that it needs to respond, to conduct inspections and to communicate important information with the establishment via the mass mailing system.4, 5

Question 2

What are some examples of how you can claim substantial equivalence other than a direct one to one comparison of a product [such as company 'A' has an orthopedic plate used for fixation of forearm fractures and your company is introducing a plate for the same indications with essentially the same features]?

Answer: Substantial equivalence means that the new device is at least as safe and effective as the predicate8.

A device is substantially equivalent to a predicate if it has the same intended use and technological features OR if it has the same intended use but different technological features that do not give rise to additional questions on safety and efficacy AND the device is at least safe and effective as the predicate8.

Apart from a direct one to one comparison of the product there are other ways to confirm substantial equivalence of the new product and the predicate. These include similarity in intended use, design, chemical composition, manufacturing process, performance, safety, effectiveness, labeling, biocompatibility, standards, and other characteristics, as applicable8.

Some examples of substantially equivalent devices that have equivalence other than direct one tone comparison are:

A toothbrush with antibacterial coated bristles as compared to a regular toothbrush.

A metal implant that holds two pieces of a fractured bone by ‘hinging’ them or by any other means other than a plate and screw construct.

Question 3

Compare the product description with predicate.

Answer: Example I

Approved medical device

Pearl Diabetes Management System (K100567)15

Predicate

Animas Model IR 1200

(K032257)16

Continuous, programmable insulin delivery system with no infrared user interface

Continuous, programmable insulin delivery system with no infrared user interface

Single use pump

Multiple use pump

Occlusion sensor present

Occlusion sensor absent

Pump provides drive mechanism and battery power

Pump incorporates serial infusions by means of an infrared user interface

Described differences : The differences in the user interfaces (infrared and non-infrared), single and multiple use mechanisms and occlusion sensors are all technical and configurational differences. The end use and indication of use is same.

Thus they are have substantial equivalence but not a direct one to one comparison.

Example II

Approved medical device

Omnipod Insulin management system

(K122953)13

Predicate

iXL II diabetes management system

(K042792)14

Made up of disposable insulin infusion pump and associated wireless remote controller

Made up of disposable insulin infusion pump and associated wireless remote controller and electroluminescent backlit liquid crystal display

Described differences: In the above example the ‘electroluminescent backlit liquid crystal display’ is the only mentioned prominent difference in 510 K of the predicate. The technology and indications of use as well as design features are exactly similar There appears to be a one-to one direct comparison.

Question 4

Please provide a recommended plan of action to reduce the possibility of this situation occurring. If this scenario did occur, what would be next steps in order for this clinical investigation to begin?

Answer:

To reduce the possibility that IRB disagrees with the determination that the device is a non-significant risk device there should be sufficient amount of data provided to IRB to conclude the safety of the device.

The other solution could be to design the clinical trial design in such a way that participating patients are exposed to minimum risk and provide mechanisms to assure safety of patients in case of an untoward event that arises during the trial.

If one of the IRB’s disagree with my company’s determination that the device is a non-significant risk device, the study would require an IDE and the study would be monitored by the IRB as well as the FDA. As a sponsor company I cannot challenge the IRB’s decision and would go forward with the IDE.

However, if the FDA rejects the IDE stating that the device is a non-significant risk device, I would request the IRB to reevaluate its decision9.

Question 5a

You are conducting your quarterly clinical monitoring visit at one of your clinical sites. You audit reveals that the investigator is entering patients that do not meet the inclusion criteria of the clinical protocol. What is your plan of action to address this issue? Do you address the issue immediately? Please provide your recommendations using the regulations as a basis for your decision.

Answer: The recruitment of patients who do not meet the inclusion criteria is a serious concern as it may be harmful to the patients and detrimental to the trial. I would address this issue immediately. As per the provisions under 21 CFR 812.46 it is my responsibility as a sponsor to seek compliance from the investigator.

Following the provisions mentioned under 21 CFR 812.46, I would seek compliance from the investigator as the first step or move forward to discontinue shipments of the device to the investigator and terminate the investigator’s participation in the clinical trial10.

Question 5b

What would you recommend to the investigator in order to support him in his quest to help these "other" patients?

Answer: Since the investigator believes that the device would be useful to a group of people outside the inclusion criteria the only way to support his desire would by going for the ‘Compassionate use’ provision and submit an IDE supplement requesting a protocol deviation under 21 CFR 812.35(a)11.

However, this decision would be taken after closely following the trials for some more time. Although by supporting the investigator and going for additional trials would mean additional financial burdens and delays in trial, it would be a risk worth taking if it benefits patients.

Question 6

Case Study

Answer:

Since it is evident that the device in discussion is a medical device my first step would be to determine the class of the device.

After searching for similar devices on the FDA’s medical device search database it is conformed that this device has predicates and taking into consideration its technical description, use and location of use (inside the body as an implant) I conclude it to be a Class II medical device with significant risk potential.

Due to the significant risk potential, the device will require an Investigational Device Exemption (IDE).

The first step now would be to gather as much possible data about the technical details of the device and its comparisons with other similar devices.

Then the team would forward a Pre-IDE meeting request to FDA to understand more on the details to be focused in the clinical development plan and understand FDA’s expectations.

Then the plan of the trial will be submitted to IRB for review and approval.

After IRB approval IDE submission will be done.

Next, if approved the trials will begin and data will be collected.

After the trials are over and reports are submitted to FDA, a traditional 510 K will be submitted with data obtained from trials and information about predicate devices.

510 K submission will be done and the device awaits approval.

Although the company has plans to complete the regulatory submission in 3 months, the practical time required could be more than expected. Also after the device approval, a special 510 K shall be submitted to approve the modifications in the product.

Question 7

When do you think that it would be appropriate to request that FDA re‐classify (down classify) a device?

Answer: A sponsor may request FDA to re-classify (down classify) a device if he intends to seek marketing approval for a device by not submitting the PMA. Due to the huge costs, extensive research and time requirements that PMA entails, the sponsor may chose to request FDA a down classification of a class III device to device to class II or even class I.

It would be appropriate for the sponsor to request a down classification of a device if he indicates that there is sufficient data available to conclude that the device is safe and effective.

The FDA could accept the sponsor’s request and down classify the device to class II if sufficient data is provided that proves that special controls (performance standards, postmarket

surveillance etc12.) assure the device’s safety and effectiveness and that general controls do not assure safety and effectiveness12.

The FDA could accept the sponsor’s request and down classify the device to class I if data provided proves that general controls (like compliance to Quality system regulations, establishment registration and device listing12 etc.) could assure safety and effectiveness of the device112.

Can you think of any reason requesting re­classification of a medical device might place a company at a disadvantage?

Answer: Requesting a reclassification of a medical device might place a company at disadvantage in the following ways:

The down classification of a device may make the way of approval easy for the competitors as they may follow the sponsor company’s path of 510K or 510 K exempted approval and launch their products in the market. Thus, this may give rise to increase in similar devices and market competition.

The delays in reclassification may cause lose of time and delayed marketing approval12.