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Section 3:

Regulatory Pathways

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Device Classification

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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

44%

55%

1%

Approved Cleared Exempt

PMA: Class III

Cleared510(k):Class II

Exempt510(k):Class I

Source: FDA, 2003

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FDA Regulatory Pathways

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Three Steps to Obtaining Marketing Clearance from FDA

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 FDA’s investigational device exemption (IDE) regulation

Step 2:• Determine the class of your device (I, II, or III)

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

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

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Pre-market Notification vs. Pre-market Approval

Pre-market Notification

510(k)

Requires:

Demonstration of Substantial Equivalence to

Predicate Device(s)*

“As safe and effective as the predicate device(s)”

Classes: I, II, some III

Pre-market Approval

PMA

Requires:

Demonstration of Reasonable Safety and

Effectiveness

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))

• 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

Same intended use as predicate device?

Yes

Same technological characteristics as the

predicate device?

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

No

Yes

Yes

SUBSTANTIALLY EQUIVALENT

NOT SUBSTANTIALLY EQUIVALENT

No

No

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Investigational Device Exemption (IDE)

• IDE according to 21 CFR 812:

� Allows investigational devices to be distributed for purposes ofconducting a clinical study

� Clinical studies conducted to collect safety and effectivenessdata in support of a premarket notification (510(k)) or premarketapproval (PMA)

• Basis for IDE:

�Proof of reasonable safety and effectiveness profiles in benchand animal testing

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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 previouslyanswered; preliminary safety data

� Safety studies (phase II): finalize design and protocol of study;investigate safety in limited number of patients; preliminaryeffectiveness data; info needed for pivotal study

�Pivotal Safety and Effectiveness Study: controlled trial, if possiblemasked, 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 FDA’s Website

e.g., Recent Device Approvals:

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

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FDA – Key Performance Indices

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TYPE OF SUBMISSION TO CDRH FY1999 FY2000 FY2001 FY2002 FY2003 FY2004

Original PMAs �� �� �� �� �� ��

PMA Supplements ��� ��� ��� ��� ��� ��

Original IDEs �� �� ��

���

�� ��� ���

IDE Amendments ��� ��� ��� ��� ���

IDE Supplements ����� �� ���� ����� ����� ����

510(k)s ������������� ��� � ������������� ��� � ������������� ��� � ������������� ��� � ���� 4,458 4,202 4,248 4,320 4,247 3,635

Original HDE �� �� � � �� �

HDE Supplements � �� �� �� �� ��

���� ���� ���� ���� �������������������� �������������������� �������������������� ���������������� ���������������� ��������������������

Types and Numbers of Applications Submitted to FDA

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

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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

Office of Device

Evaluation

- Several divisions for

particular types of devices

Office of Surveillance

and Biometrics

- Division of PostmarketSurveillance

- Product Evaluation

Branch

- Epidemiology Branch

Office of Compliance

- Enforcement

Office of Science and Technology

- Research

Pre-Market Post-Market