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Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices: Guidance for Industry and Food and Drug Administration Staff

FinalCenter for Devices and Radiological Health08/27/2014

Description

FDA is issuing this guidance to provide industry and agency staff with recommendations for studies to establish the analytical and clinical performance of highly multiplexed microbiological/medical countermeasure in vitro nucleic acid based diagnostic devices (hereafter referred to as HMMDs) intended to simultaneously detect and identify multiple pathogen nucleic acids extracted from a single appropriate human specimen or culture. For the purposes of this guidance document, the multiplex level that is used to define HMMDs is the capability to detect ≥20 different organisms/targets, in a single reaction, using a nucleic acid-based technology and involves testing multiple targets through a common process of specimen preparation, amplification and/or detection, and result interpretation. HMMDs are used to aid in the diagnosis of infection or screening for colonization. This guidance is not intended to replace or supersede other assay specific guidance documents.

Scope & Applicability

Product Classes

7
Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices

The primary subject of the guidance, defined as HMMDs.; Subject of the guidance document; The subject of the guidance document.; Subject of the guidance document regarding clinical evaluation and post-market analysis.

cleared device

perform an evaluation of the cleared device (i.e., device without new analyte) and the modified version.

HMMD

Abbreviation for Highly Multiplexed Microbiological Diagnostic devices.

Qualitative tests

tests that have an underlying numerical output or estimate overall variance

HCT/Ps

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

Class II premarket devices

FDA provides recommendations for data submission for these devices

Class III

Class III subject to the 510(k) or PMA requirements

Stakeholders

2
Manufacturer

Entity responsible for submitting NDINs

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Attributes

8
Intended Use

Evidence of a new intended use based on communications

95% CI

Present results as a mean and associated 95% two-sided CI

Positive percent agreement

Clinical performance metric requiring a minimum of 50 positive specimens per organism.

Negative percent agreement

Clinical performance metric evaluated using prospectively collected specimens.

Quality score of 20 or higher

Acceptable quality for generated sequences as measured by PHRED.

Moderate level of concern

In vitro diagnostic devices of this type are typically considered a moderate level of concern

Cut-off

The value used to distinguish positive from negative results.

Cut-off values

Values defining positive, negative, or invalid results

Identified Hazards

Hazards

6
Cross-contamination

Risk associated with construction, traffic flow, and shared equipment.; Risk from raw food to RTE food or from insanitary objects; Personnel handling RTE foods touch contaminated surfaces

Competitive Interference

Evaluation of competitive interference and interference from other microbes should be done for the new analyte.

Cross-reactivity

Potential for the assay to react with non-target pathogens.; Evaluation of cross-reactivity should be done for the new analyte based on section 6.B.iii.

Interference

Endogenous and exogenous interference studies

False positive result

Risk leading to unnecessary treatment for acute radiation syndrome.

False negative result

Risk leading to failure to provide lethal-prevention treatment.

Related CFR Sections (3)

Related Warning Letters (10)

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    2025-10-07
  • Medical Device/Adulterated/Misbranded/Lacks PMA and/or 510(k)

    The Richline Group, Inc.

    2025-09-23
  • Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA) Adulterated Device

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See Also (8)

Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices: Guidance for Industry and Food and Drug Administration Staff | Guideline Explorer | BioRegHub