Section 3:

Regulatory Pathways

Device Classification

FDA Device Classification: Risk-Based Approach

Class 1:

Common, low-risk devices

General controls
Most exempt from pre-market submission

Class 2:

More complex, higher risk

Special controls
Pre-market notification [510(k)]

Class 3:

Most complex, highest risk

(Devices which support or sustain human life; devices which
pose potential unreasonable risk of illness or injury)
Comprehensive data needed
Pre-market application [PMA]
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Percentage of Devices in Different Categories

Exempt
510(k):
Class I

PMA:
Class III
1%

44%

55%

Approved

Cleared

Cleared
510(k):
Class II

Exempt
Source: FDA, 2003

FDA Regulatory Pathways

Three Steps to Obtaining Marketing Clearance from FDA

Step 1:
Make sure the product that you wish to market is in fact a medical device

Step 2:

Determine the class of your device (I, II, or III)

This classification will identify the marketing process: 510(k) or PMA

Step 3:

Develop data and/or information that is necessary to submit application

For some 510(k)s and most PMAs, clinical performance data is required;
In these cases, a trial must be conducted in accordance with FDAs
investigational device exemption (IDE) regulation
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Pre-market Notification vs. Pre-market Approval

Pre-market Notification

Pre-market Approval

510(k)

PMA

Requires:

Requires:

Demonstration of
Substantial Equivalence to
Predicate Device(s)*

Demonstration of
Reasonable Safety and
Effectiveness

As safe and effective as

the predicate device(s)
Classes: I, II, some III

Class: III

* Device that is not subject to PMA;

predicate devices: legally marketed before
May 28, 1976 (preamendments device), or
device that has been reclassified from class
III to class II or I, or device that has been
found SE to one of these devices through
the 510(k) process.
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Determination of Substantial Equivalence (510(k))

Same intended use as
predicate device?

No

NOT SUBSTANTIALLY
EQUIVALENT
No

Yes
Same technological
characteristics as the
predicate device?

Yes

No

Different technological
characteristics that do not
raise new questions of safety
and effectiveness & sponsor
shows that the device is as
safe and effective as the
predicate device
Yes

SUBSTANTIALLY EQUIVALENT

Requirement: Descriptive data; in about 10-15% of cases performance data

Type of study dictated by: ability of bench and animal testing to answer
questions; amount of difference between subject and predicate device
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Investigational Device Exemption (IDE)

IDE according to 21 CFR 812:
Allows investigational devices to be distributed for purposes of
conducting a clinical study
Clinical studies conducted to collect safety and effectiveness
data in support of a premarket notification (510(k)) or premarket
approval (PMA)
Basis for IDE:
Proof of reasonable safety and effectiveness profiles in bench
and animal testing

Pre-market Approval (PMA) Application

Establish safety and effectiveness
Usual process: bench animal clinical (human) testing
Investigational device exemption (IDE) needed for human testing
Feasibility studies: answer design-related questions not previously
answered; preliminary safety data
Safety studies (phase II): finalize design and protocol of study;
investigate safety in limited number of patients; preliminary
effectiveness data; info needed for pivotal study
Pivotal Safety and Effectiveness Study: controlled trial, if possible
masked, method of use consistent with proposed labeling,
statistical validity.
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Other Relevant ODE Programs

Humanitarian Device Exemptions (HDEs)
Essentially same as PMA in both form and content, but exempt from the
effectiveness requirement
Approved HDE authorizes marketing of the humanitarian use device
(HUD)
Available if < 8,000 patients / year have the condition to be treated

Product Development Protocols (PDPs)

Second designated pathway for class III devices (introduced 1976)
Based upon early consultation between the sponsor and the FDA
leading to device development and testing plan acceptable to both
parties
Seldomly used
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Clinical Trials and Study Design

Questions of appropriate endpoints:
Physiological endpoints (e.g., plasma levels, blood pressure measurements)
Clinical events (e.g., hospitalizations, symptoms, functional capacity)
Mortality
Surrogate endpoints
use when true endpoint is rare, delayed, confounded, etc.
valid if surrogate endpoint is correlated with true clinical endpoint

Questions of study design:

Type of control used; inclusion/exclusion criteria, monitoring, statistical
methodology, analysis of potential biases and of covariates
Sources: Prentice 1989; FDA, 2003

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Device and Approval Information on FDAs Website

e.g., Recent Device Approvals:

http://www.fda.gov/cdrh/consumer/mda/

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FDA Key Performance Indices

14

Types and Numbers of Applications Submitted to FDA

TYPE OF SUBMISSION
TO CDRH

FY1999

FY2000

FY2001

FY2002

FY2003

FY2004

4,458

4,202

4,248

4,320

4,247

3,635

Original PMAs
PMA Supplements
Original IDEs
IDE Amendments
IDE Supplements

510(k)s
Original HDE
HDE Supplements

Source: FDA ODE Annual Report FY 2004

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FDA Key Performance Indices: 510(k)

Average 510(k) Review Time for Decision Cohort

Source: FDA ODE Annual Report FY 2004

16

FDA Key Performance Indices: PMA

Original Receipt Cohort PMAs Received and Filed

Receipt Cohort PMA Average Elapsed Time from

Filing to Final Action

Source: FDA ODE Annual Report FY 2004

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FDA Key Performance Indices: IDE

Percentage of IDEs Approved on First Review Cycle

Source: FDA ODE Annual Report FY 2004

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Overview of FDA Pre- and

Postmarket Activities

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FDA: Evaluation During All Stages of Device Lifecycle

Pre-Market

Post-Market

Office of
Device
Evaluation

Office of
Surveillance
and Biometrics

- Several
divisions for
particular types
of devices

- Division of
Postmarket
Surveillance

Office of
Compliance

Office of
Science and
Technology

- Enforcement

- Research

- Product

Evaluation
Branch
- Epidemiology
Branch
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