US Food and Drug Administration Perspectives on Clinical Mass Spectrometry

Abstract Mass spectrometry–based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry–based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry–based devices and enhance their entry into the clinic.

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Verification of Performance Specifications of a Molecular Test: Cystic Fibrosis Carrier Testing Using the Luminex Liquid Bead Array

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2010-0536-oa ◽

2012 ◽

Vol 136 (1) ◽

pp. 14-19 ◽

Cited By ~ 6

Author(s):

Felicitas L Lacbawan ◽

Karen E Weck ◽

Jeffrey A Kant ◽

Gerald L Feldman ◽

Iris Schrijver ◽

...

Keyword(s):

Cystic Fibrosis ◽

Drug Administration ◽

Clinical Laboratory ◽

Food And Drug Administration ◽

Carrier Testing ◽

Clinical Diagnostic Laboratory ◽

Cystic Fibrosis Carrier ◽

Performance Specifications ◽

In Vitro Diagnostic

Context.—The number of clinical laboratories introducing various molecular tests to their existing test menu is continuously increasing. Prior to offering a US Food and Drug Administration–approved test, it is necessary that performance characteristics of the test, as claimed by the company, are verified before the assay is implemented in a clinical laboratory. Objective.—To provide an example of the verification of a specific qualitative in vitro diagnostic test: cystic fibrosis carrier testing using the Luminex liquid bead array (Luminex Molecular Diagnostics, Inc, Toronto, Ontario). Design.—The approach used by an individual laboratory for verification of a US Food and Drug Administration–approved assay is described. Results.—Specific verification data are provided to highlight the stepwise verification approach undertaken by a clinical diagnostic laboratory. Conclusions.—Protocols for verification of in vitro diagnostic assays may vary between laboratories. However, all laboratories must verify several specific performance specifications prior to implementation of such assays for clinical use. We provide an example of an approach used for verifying performance of an assay for cystic fibrosis carrier screening.

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Regulation of Medical Devices by the Food and Drug Administration * with Emphasis on In Vitro Diagnostic Devices

10.1201/9780429179587-7 ◽

2021 ◽

pp. 77-88

Author(s):

Peter E. Maxim ◽

Steven I. Gutman

Keyword(s):

Drug Administration ◽

Medical Devices ◽

Food And Drug Administration ◽

In Vitro Diagnostic

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Food and Drug Administration (FDA)'s impact on laboratory performance: FDA's perspective

Clinical Chemistry ◽

10.1093/clinchem/42.5.786 ◽

1996 ◽

Vol 42 (5) ◽

pp. 786-789

Author(s):

S Gutman

Keyword(s):

Drug Administration ◽

De Novo ◽

Clinical Laboratory ◽

Food And Drug Administration ◽

Scientific Review ◽

Regulatory Issue ◽

In Vitro Diagnostic ◽

Intended Use

Abstract The Division of Clinical Laboratory Devices is responsible for the premarket review of in vitro diagnostic devices (laboratory tests). We currently process >1000 diverse applications per year. New versions of old devices are handled as premarket notifications, so-called 510(k) submissions. The review objective is to establish that the new product is "substantially equivalent" to its predicate. Fundamentally new devices are handled as premarket applications. The review objective is to establish de novo that the product is ¿safe and effective.¿ A central regulatory issue over the past several years has been the development of a standardized model for scientific review. The Food and Drug Administration contributes to the quality of in vitro diagnostic devices by providing oversight and objective review, by setting thresholds for product safety and effectiveness, and by ensuring that organized data and appropriate labeling is present in support of a device's intended use.

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The Role of Food and Drug Administration Regulation of In Vitro Diagnostic Devices—Applications to Genetics Testing

Clinical Chemistry ◽

10.1093/clinchem/45.5.746 ◽

1999 ◽

Vol 45 (5) ◽

pp. 746-749 ◽

Cited By ~ 26

Author(s):

Steven Gutman

Keyword(s):

Drug Administration ◽

Human Services ◽

Food And Drug Administration ◽

Building Blocks ◽

Advisory Panel ◽

Department Of Health ◽

In Vitro Diagnostic

Abstract The Food and Drug Administration (FDA) has been involved in the regulation of in vitro diagnostic devices (IVDs or laboratory tests) since the introduction of the Medical Device Amendments of 1976. IVDs developed as kits or systems intended for use in multiple laboratories require review by the FDA before being marketed to ensure appropriate performance and labeling. IVDs developed as in-house, or so-called “home-brew”, tests or laboratory test services are considered medical devices, but historically have not been subject to premarket review as a matter of enforcement discretion. FDA recently established a new regulatory paradigm for in-house tests based on classification of the active ingredients or building blocks of these tests as analyte-specific reagents (ASRs). ASRs are exempt from premarket review but subject to both manufacturing and labeling controls. Currently, genetic tests are received and reviewed by the FDA in the same manner as other in vitro diagnostic tests. The FDA currently is in the process of chartering a new genetics advisory panel to provide the agency with outside expertise to deal with genetic testing issues. We are also continuing to work with other agencies within the Department of Health and Human Services to determine how we can cooperatively help foster this important new area of testing.

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Protein-Based Multiplex Assays: Mock Presubmissions to the US Food and Drug Administration

Clinical Chemistry ◽

10.1373/clinchem.2009.140087 ◽

2010 ◽

Vol 56 (2) ◽

pp. 165-171 ◽

Cited By ~ 56

Author(s):

Fred E Regnier ◽

Steven J Skates ◽

Mehdi Mesri ◽

Henry Rodriguez ◽

Živana Težak ◽

...

Keyword(s):

Drug Administration ◽

Task Force ◽

Food And Drug Administration ◽

Protein Quantification ◽

Diagnostic Device ◽

Multiplex Assays ◽

Array Platform ◽

The Us ◽

In Vitro Diagnostic

Abstract As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomic Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and Drug Administration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays.

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