Presented by:Mr.SURAJ P.S

1st M. Pharm-RA

JSSCP, Mysore.

APPROVAL PROCESS FOR MEDICAL DEVICES IN UNITED STATES

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What is medical device?

•"an instrument, apparatus, implement, machine, contrivance, implant, in

vitro reagent, or other similar or related article, including a component part,

or accessory which is:

• recognized in the official National Formulary, or the United States

Pharmacopoeia, or any supplement to them,

• intended for use in the diagnosis of disease or other conditions, or in

the cure, mitigation, treatment, or prevention of disease, in man or

other animals, or

• intended to affect the structure or any function of the body of man or

other animals, and which does not achieve its primary intended

purposes through chemical action within or on the body of man or

other animals and which is not dependent upon being metabolized for

the achievement of any of its primary intended purposes."

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Classification of medical device

Class I

Class I Medical Devices are simple in design and have little to no potential

risk. Medical devices classified as type I must follow general FDA policy

which includes registering the medical device,

proper branding and labeling,

proper manufacturing techniques

and

the FDA must be notified prior to marketing the device. Class I Medical

Devices include tongue depressors, elastic bandages, hand held dental

instruments and examination gloves.

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Cont…..

Class II

Class II Medical devices are more complicated in design and pose a minimal

risk. Medical devices classified as type II must follow general policy and

special labeling, mandatory performance standards and post market

surveillance.

Most medical devices fall into the Class II medical devices category such as X-

ray machines, powered wheelchairs, infusion pump and surgical and

acupuncture needles.

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Class III• Class III Medical Devices are intricate in design and have the strictest guidelines

because they pose the greatest risk. Class III Medical Devices must follow Class I

and Class II guidelines but must also be pre-market approved by the FDA and a

scientific review of the medical device must be made prior to marketing.

• Class III medical devices support or sustain human lives therefore malfunction is

absolutely unacceptable.

• Class III Medical Devices include implanted pacemakers, heart valves and implanted

cerebral simulators.

Cont…..

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• Code of Federal Regulations (CFR), Title 21, Parts 862–892

• Medical Device Directive 93/42/EEC regulates most devices.

Classification rules are listed in Annex IX of the directive.

• Active Implantable Medical Devices (AIMDs) Directive 90/385/EEC.

AIMDs are regulated as high-risk devices.

• In Vitro Diagnostics (IVDs) Directive 98/79/EC. Most IVDs are

regulated as low-risk devices, except for tests that underpin the safety of

blood and blood products (blood group, HIV and hepatitis tests), where

additional specific requirements equating to a high-risk category apply.

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REGULATION’S

Overview of Device Regulation

• Medical devices are classified into Class I, II, and III.

• Regulatory control increases from Class I to Class III.

• The device classification regulation defines the regulatory

requirements for a general device type.

• Most Class I devices are exempt from Premarket Notification

510(k);

• Most Class II devices require Premarket Notification 510(k);

and

• Most Class III devices require Premarket Approval. 7

Establishment Registration

• Manufacturers (both domestic and foreign) and initial distributors

(importers) of medical devices must register their establishments with the

FDA.

• All establishment registrations must be submitted electronically.

• All registration information must be verified annually between October 1st

and December 31st of each year.

• In addition to registration, foreign manufacturers must also designate a

U.S. Agent. Beginning October 1, 2007, most establishments are required

to pay an establishment registration fee.

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Premarket Notification 510(k)

• If sponsor device requires the submission of a Premarket Notification 510(k),

sponsor cannot commercially distribute the device until you receive a letter

of substantial equivalence from FDA authorizing you to do so.

• A 510(k) must demonstrate that the device is substantially equivalent to one

legally in commercial distribution in the United States:

(1) before May 28, 1976; or

(2) to a device that has been determined by FDA to be substantially

equivalent.

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Premarket Notification (510k)

The sponsors who wants to market in the U.S., a Class I, II, and III

device intended for human use, must submit a 510(k) to FDA unless the

device is exempt from 510(k) requirements of the Federal Food, Drug,

and Cosmetic Act

A 510(k) is a premarket submission made to FDA to demonstrate that the

device to be marketed is at least as safe and effective, that is, substantially

equivalent, to a legally marketed device.

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Premarket Approval (PMA)

• Premarket approval (PMA) is the FDA process of scientific and regulatory

review to evaluate the safety and effectiveness of Class III medical

devices.

• FDA has determined that general and special controls alone are

insufficient to assure the safety and effectiveness of class III devices.

Therefore, these devices require a premarket approval (PMA) application

• PMA approval is based on a determination by FDA that the PMA contains

sufficient valid scientific evidence to assure that the device is safe and

effective for its intended use(s).

• FDA regulations provide 180 days to review the PMA and make a

determination.

• PMA devices often involve new concepts and many are not of a type

marketed prior to the Medical Device Amendments. Therefore, they do not

have a classification regulation in the CFR.

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Data Requirements – PMA

A Premarket Approval (PMA) application is a scientific, regulatory

documentation to FDA to demonstrate the safety and effectiveness of the

class III device.

Technical Sections

Non-clinical Laboratory Studies Section

Clinical Investigations Section

What is Substantial Equivalence?

A 510(k) requires demonstration of substantial equivalence to another legally

U.S. marketed device. Substantial equivalence means that the new device is at

least as safe and effective as the predicate.

A device is substantially equivalent if, in comparison to a predicate it:

•has the same intended use as the predicate; and

•has the same technological characteristics as the predicate;

Substantial equivalence is established with respect to intended use,

design, energy used or delivered, materials, chemical composition,

manufacturing process, performance, safety, effectiveness, labeling,

biocompatibility, standards, as applicable. 13

Who is Required to Submit a 510(k) ?

1. Domestic manufacturers introducing a device to the U.S. market;

2. Specification developers introducing a device to the U.S. market;

3. Repackers or relabelers who make labeling changes or whose

operations significantly affect the device.

4. Foreign manufacturers/exporters or U.S. representatives of foreign

manufacturers/exporters introducing a device to the U.S. market.

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When a 510(k) is Not Required ?

1. You sell unfinished devices to another firm for further processing or

sell components to be used in the assembling of devices by other

firms.

2. Your device is not being marketed or commercially distributed. You

do not need a 510(k) to develop, evaluate, or test a device. This

includes clinical evaluation.

3. You distribute another firm's domestically manufactured device. You

may place a label on the device, "Distributed by ABC Firm" or

"Manufactured for ABC Firm," and sell it to end users without

submission of a 510(k).15

4. In most cases, if you are a repackager or a relabeler you are not

required to submit a 510(k) if the existing labeling or condition of the

device is not significantly changed.

5. Your device was legally in commercial distribution before May 28,

1976 and you have documentation to prove this. These devices are

"grandfathered" and have Preamendment Status.

6. The device is made outside the U.S. and you are an importer of the

foreign made medical device. A 510(k) is not required if a 510(k) has

been submitted by the foreign manufacturer and received marketing

clearance.

Cont….

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Approval

Process

Using the FDA classification database, determine the classification of your device by

researching “Predicate Devices” already registered in the US market.

Implement Quality Management System (QMS) which meets FDA Quality System Regulation (QSR) found in 21 CFR Part 820. This is also commonly known as FDA Good Manufacturing Practice (GMP).

Innovative Class II, and all Class III, devices will likely require clinical studies.Get “Pre-Submission (Pre-Sub)” feedback from the FDA.

If clinical studies will be required, apply for an

Investigational Device Exemption (IDE). Develop clinical trial

protocol and conduct studies.* 18

Prepare and submit 510(k) premarket notification

application. Pay 510(k) review fee to FDA. Prepare and

submit Premarket Approval (PMA) application. Pay PMA

submission fee to FDA.

FDA conducts facility inspections of all

major suppliers involved in the design and

production of your device. All parties must

be compliant with FDA QSR

FDA issues 510(k) clearance letter; posts online. FDA issues

PMA approval letter; posts online.

At this time, sponsor must be in full compliance with QSRs. The FDA will not inspect

Class I or II device manufacturers for compliance prior to device registration but does

conduct random inspections and can issue a Form 483 for non-compliance. 19

If you have no local presence in the US, appoint an FDA US Agent representative as a

local point of contact with the FDA.

List your device and register your company using FURLS system on the FDA website

in accordance with 21 CFR Part 807; contract manufacturers and sterilizers must also

register and list. Specify your appointed US Agent. Your FDA Establishment

Registration and Listing must be renewed on a yearly basis

You are now able to sell your device in the US. The FDA listing on their website will

serve as your authorization to commercialize your device in the US. This authorization

does not expire as long as certain types of changes are not made, e.g., design, intended

use.20

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510(k) Components

Main component of 510 (k) are:

1. Cover Sheet

2. Cover Letter

3. Table of Contents

4. Labelling

5. Comparative Information

6. Biocompatibility Assessment (If Necessary)

7. Clinical Data

8. Shelf Life (If Necessary)

9. Indication for Use

10. 510 (k) Summary

REFERENCE’S

1. http://neverusewhiteout.blogspot.in/2013/04/fda-proposes-change-to-device-

labels.html

2. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm

3. http://www.fda.gov/aboutfda/transparency/basics/ucm211822.htm

4. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/def

ault.htm

5. http://www.fda.gov/medicaldevices/deviceregulationandguidance/overview/classi

fyyourdevice/ucm051512.htm definition

6. http://www.litron.com/Classification-of-Medical-Devices.asp classification

7. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm CFR

8. www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ overview

9. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarket

YourDevice/PremarketSubmissions/PremarketApprovalPMA/default.htm#top

10. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarket

YourDevice/PremarketSubmissions/PremarketNotification510k/ucm142651.htm

contents of 510k 22

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