Difference between revisions of "Journal:The regulatory landscape of precision oncology laboratory medicine in the United States: Perspective on the past five years and considerations for future regulation"
Shawndouglas (talk | contribs) (Saving and adding more.) |
Shawndouglas (talk | contribs) (Saving and adding more.) |
||
| Line 40: | Line 40: | ||
The FDA has maintained that they have the statutory authority to regulate all laboratory tests, including tests that are developed and offered in a single lab, but have chosen to operate under a policy of enforcement discretion. | The FDA has maintained that they have the statutory authority to regulate all laboratory tests, including tests that are developed and offered in a single lab, but have chosen to operate under a policy of enforcement discretion. | ||
==Emergence of new regulatory proposals== | |||
===2014 draft guidance and evolution to legislation=== | |||
In October of 2014, the U.S. FDA released draft guidance<ref name="FDAFramework14">{{cite web |url=https://www.fda.gov/media/89841/download |title=Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) - Draft Guidance |author=Food and Drug Administration |publisher=Food and Drug Administration |date=03 October 2014 |accessdate=31 August 2019}}</ref> that proposed to dramatically change the regulatory landscape of tests that were developed and offered in a single laboratory, formally referred to as "laboratory developed tests" or LDTs. There was a large amount of feedback from academic, community, commercial, and professional stakeholders, with several hundred comments submitted to the FDA docket.<ref name="FDAFrameworkDocket15">{{cite web |url=https://www.regulations.gov/docket?D=FDA-2011-D-0360 |title=Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) |author=Food and Drug Administration |work=Regulations.gov |date=02 February 2015 |accessdate=31 August 2019}}</ref> After the 2016 presidential election, the FDA publicly stated that the agency will defer to the legislative branch of the U.S. government to update the regulatory landscape of LDTs and manufactured laboratory tests, also know as ''in vitro'' diagnostic devices.<ref name="FDADiscussion17">{{cite web |url=https://www.fda.gov/media/102367/download |title=Discussion Paper on Laboratory Developed Tests (LDTs) |author=Food and Drug Administration |publisher=Food and Drug Administration |date=13 January 2017 |accessdate=31 August 2019}}</ref> Although the FDA has stated that it will not wholesale change the regulatory requirements for LDTs in the interim, the agency has continued to release guidance documents, in both draft and final forms, that touch on the regulation of laboratory diagnostics that are used in the care of [[oncology]] patients. | |||
Revision as of 20:12, 15 June 2020
| Full article title |
The regulatory landscape of precision oncology laboratory medicine in the United States: Perspective on the past five years and considerations for future regulation |
|---|---|
| Journal | Practical Laboratory Medicine |
| Author(s) | Konnick, Eric Q. |
| Author affiliation(s) | University of Washington |
| Primary contact | Email: konnick at uw dot edu |
| Year published | 2020 |
| Volume and issue | 21 |
| Article # | e00172 |
| DOI | 10.1016/j.plabm.2020.e00172 |
| ISSN | 2352-5517 |
| Distribution license | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International |
| Website | https://www.sciencedirect.com/science/article/pii/S2352551719301040 |
| Download | https://www.sciencedirect.com/science/article/pii/S2352551719301040/pdfft (PDF) |
 |
This article should be considered a work in progress and incomplete. Consider this article incomplete until this notice is removed. |
Abstract
The regulatory landscape for precision oncology in the United States is complicated, with multiple governmental regulatory agencies with different scopes of jurisdiction. Several regulatory proposals have been introduced since the Food and Drug Administration released draft guidance to regulate laboratory developed tests in 2014. Key aspects of the most recent proposals and discussion of central arguments related to the regulation of precision oncology laboratory tests provides insight to stakeholders for future discussions related to regulation of laboratory tests.
Keywords: oncology, regulation, testing, LDTs, FDA, CLIA, CMS
The current regulatory environment in the United States
The current state of laboratory test regulation in the United States (U.S.) is complex, and the prospect of changes in the current paradigm has been continually on the horizon since 2014. Briefly, clinical laboratories in the U.S. are regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ′88)[1] of the Public Health Services Act, which are administered by the Centers for Medicare and Medicaid Services (CMS). These regulations were put in place to improve the quality of the processes in clinical laboratories, but the regulations allow for organizations that have received certification from CMS to inspect laboratories as a deemed entity. This status allows deemed entities to place additional requirements in place, so long as the underlying CLIA requirements are met.
CLIA regulations have a flexible framework that allows individual medical directors and laboratories to have some leeway in how the specific requirements are met, which allows for accommodation of unique population-, laboratory-, and test-level factors that can improve the overall quality of testing, while also allowing for the development of tests by laboratory medicine practitioners within certain bounds. Testing kits that are manufactured and shipped across state lines are regulated by the U.S. Food and Drug Administration (FDA) via the Medical Device Amendments of 1976[2], which amended the Federal Food, Drug, and Cosmetic Act of 1938. The FDA has several review and approval pathways where the manufacturer submits documentation and data to the FDA for review, and if the data fulfill the FDA’s requirements, the test recieves marketing authorization. Manufacturers can then sell their products to laboratories, who wish to perform that testing.
Testing kits which are cleared or approved by the FDA are regulated under CLIA when they are performed in a certified laboratory. In addition, under the current structure, laboratories are expected to verify the performance of these products and, under CLIA, are allowed to modify them if deemed necessary by medical leadership. If a manufactured product is modified by the user's laboratory, the test is considered a "laboratory developed test." Such modifications are frequently made to improve assay performance, use the assay in a way different from the use claimed by the manufacturer (e.g., diagnostic instead of screening applications), or allow acceptance of additional sample types that were not submitted to the FDA for approval. This regulatory flexibility allows clinical laboratories to offer tests that are accurate and medically relevant to their patients. Currently, many high-complexity clinical laboratories are accredited by the College of American Pathologists (CAP), which conducts unannounced biannual laboratory inspections and administers a multitude of proficiency testing programs to evaluate the accuracy and agreement between laboratories across the spectrum of laboratory tests.
The FDA has maintained that they have the statutory authority to regulate all laboratory tests, including tests that are developed and offered in a single lab, but have chosen to operate under a policy of enforcement discretion.
Emergence of new regulatory proposals
2014 draft guidance and evolution to legislation
In October of 2014, the U.S. FDA released draft guidance[3] that proposed to dramatically change the regulatory landscape of tests that were developed and offered in a single laboratory, formally referred to as "laboratory developed tests" or LDTs. There was a large amount of feedback from academic, community, commercial, and professional stakeholders, with several hundred comments submitted to the FDA docket.[4] After the 2016 presidential election, the FDA publicly stated that the agency will defer to the legislative branch of the U.S. government to update the regulatory landscape of LDTs and manufactured laboratory tests, also know as in vitro diagnostic devices.[5] Although the FDA has stated that it will not wholesale change the regulatory requirements for LDTs in the interim, the agency has continued to release guidance documents, in both draft and final forms, that touch on the regulation of laboratory diagnostics that are used in the care of oncology patients.
References
- ↑ "Public Law 100-578 - Clinical Laboratory Improvement Amendments of 1988" (PDF). U.S. Government Publishing Office. 31 October 1988. https://www.govinfo.gov/content/pkg/STATUTE-102/pdf/STATUTE-102-Pg2903.pdf. Retrieved 30 August 2019.
- ↑ "Public Law 94–295 - Medical Device Amendments of 1976" (PDF). U.S. Government Publishing Office. 28 May 1976. https://www.govinfo.gov/content/pkg/STATUTE-90/pdf/STATUTE-90-Pg539.pdf. Retrieved 31 August 2019.
- ↑ Food and Drug Administration (3 October 2014). "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) - Draft Guidance". Food and Drug Administration. https://www.fda.gov/media/89841/download. Retrieved 31 August 2019.
- ↑ Food and Drug Administration (2 February 2015). "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)". Regulations.gov. https://www.regulations.gov/docket?D=FDA-2011-D-0360. Retrieved 31 August 2019.
- ↑ Food and Drug Administration (13 January 2017). "Discussion Paper on Laboratory Developed Tests (LDTs)". Food and Drug Administration. https://www.fda.gov/media/102367/download. Retrieved 31 August 2019.
Notes
This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. Otherwise, in accordance with the NoDerivatives portion of the original license, nothing else has been changed.
