Molecular Diagnostic Instruments with Combined Functions: Guidance for Industry and Food and Drug Administration Staff

Description

This documentprovides FDA’s current thinking on regulation of molecular diagnostic instruments that combine in a single instrument both approved/cleared device functions and device functions for which approval/clearance is not required. It also provides advice on the type of information that should be provided in a premarket submission for a molecular diagnostic instrument that measures or characterizes nucleic acid analytes and has combined functions. In this document, "combined functions" refers to instruments that serve as a component of an FDA-cleared or approved IVD system but can also be configured by the user for other test purposes, such as basic research.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

3

HCT/Ps

Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271

IVD system

In vitro diagnostic system.

Molecular Diagnostic Instruments

Instruments that combine approved/cleared device functions and device functions for which approval/clearance is not required.; Instruments with combined functions for approved and non-approved uses

Stakeholders

2

Third party assay developers

Developers submitting assays to be run on user-configurable instruments

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

3

Premarket Approval

PMA application for high-risk devices

PMA

Premarket Approval Application

510(k)

Premarket notification submission type

Document Types

3

Risk/hazard analysis

Required documentation addressing coexistence of functions

Result reports

Reports that must distinguish between approved and non-approved functions.

Risk mitigation plan

Information to demonstrate risks from combined functions are mitigated.

Attributes

2

Investigational Use Only

Labeling for products used in clinical investigations.

Research Use Only

Labeling for products not intended for diagnostic procedures.

Technical Details

Substances

1

nucleic acid analytes

Analytes measured or characterized by the instruments.

Testing Methods

1

Analyte test panel

Used prior to performing an assay to verify non-interference

Processes

2

Recalibration procedures

Maintenance activity to ensure instrument performance

Instrument validation

Procedures for users to verify that non-cleared use does not interfere with cleared use.

Clinical Concepts

4

Adverse events

Safety findings including deaths and post-mortem examinations

cystic fibrosis

Example for incidence estimate in HUD request

Hepatitis C virus

Disinfectant product should be effective against this virus

MRSA

Pathogen treated by Rifamycins in combination therapy.

Related CFR Sections (3)

21CFR814.39§ 814.39 PMA supplements.
(a) After FDA's approval of a PMA, an applicant shall submit a PMA supplement for review and approval by FDA before making a change affecting the safety or effectiveness of the device for which the applicant has an approved PMA, unless the change is of a type for which FDA, under paragraph (e) of thRead full regulation →
21CFR807.81§ 807.81 When a premarket notification submission is required.
(a) Except as provided in paragraph (b) of this section, each person who is required to register his establishment pursuant to § 807.20 must submit a premarket notification submission to the Food and Drug Administration at least 90 days before he proposes to begin the introduction or delivery for inRead full regulation →
21CFR809.10§ 809.10 Labeling for in vitro diagnostic products.
(a) The label for an in vitro diagnostic product shall state the following information, except where such information is not applicable, or as otherwise specified in a standard for a particular product class or as provided in paragraph (e) of this section. Section 201(k) of the act provides that “a Read full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to adequately develop, maintain, and implement written MDR procedures

9

Adulterated under section 501(f)(1)(B)

8

Misbranded under section 502(o)

7

Failure to submit a report to FDA no later than 30 calendar days

5

Failure to adequately establish and maintain procedures for implementing corrective and preventive action

4

Failure to adequately establish and maintain procedures for design changes

4

Failure to develop, maintain, and implement written MDR procedures

4

Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints

3

Failure to establish and maintain procedures for validating the device design

3

Failure to establish and maintain procedures for implementing corrective and preventive action