In 2014, the FDA announced an extensive plan by which it would regulate laboratory-developed tests. Concerns were quickly raised that the agency's regulation process would be far to cumbersome.
The FDA has issued several guidances that so its flexibility in approaching the classification of genomic tests. More after the break.
1. Creative Positions on NGS
However, the FDA has been signaling trends toward less cumbersome regulation. Its December 2014 position paper on eventually regulating next generation sequencing garnered favorable attention through an essay by MIT's Eric Lander in the New England Journal of Medicine in March 2015. (FDA's NGS position paper here; Lander's NEJM viewpoint here. My 12/2014 blog, here.) The FDA also notes that it has recently been able to approve both CF and BRCA tests by reference to evolving rather than fixed databases (here).
2. Downclassifying Some Human Germline Genetic Tests
In February 2015, the agency announced it planned to downclassify autosomal recessive genes as Class II devices (FDA press here, Modern Healthcare here.) This was in tandem with the announcement that 23andMe could go forward with offering this type of testing on a direct-to-consumer basis. (See "Deeper Dive," below.)
3. Downclassifying Genomic Microbial Tests
In May 2015, the FDA downclassified multiple microbial nucleic acid testing to Class II as well (Federal Register, here.) FDA will also see this as building its experience with the world of multiplex testing. (Gray Sheet, June 1, here.)
4. Harmonizing Companion Diagnostics Approvals by Class.
Another example of the FDA's efforts at forward-looking flexibility was seen in a March 2015 workshop on "harmonizing" approval processes for companion diagnostics. The goal to avoid the proliferation of situations where potentially four drugs in a class are approved with four different biomarker tests kits for the very same analyte, but each test approved in only a 1:1 relationship to a drug. See workshop agenda and presentations here.
A Deeper Dive: Downclassifying Carrier Gene Screening
After a much-discussed "stop work" order from the FDA to 23andMe in November 2013, the FDA did a number of creative things by February and March 2015. First, it established carrier genetic screening - for penetrant autosomal recessive diseases - as Class II devices of a special type which do not need a 510(k) approval. This was already apparent by the FDA's detailed letter to 23andMe in February 2015, a letter than was clearly also a Trojan Horse to carrier the FDA's viewpoint to a wider public without actually releasing a guidance document. (My take on it, here.) And, they were allowed to be direct-to-consumer tests.
We can now see the official classification which will be codified at 21 CFR 866.5940 (here):
Device Autosomal Recessive Carrier Screening Gene Mutation Detection System
Definition Autosomal recessive carrier screening gene mutation detection system is a qualitative in vitro molecular diagnostic system used for genotyping of clinically relevant variants in genomic dna isolated from human peripheral whole blood or saliva specimens intended for prescription use or over-the-counter use.The device is intended for autosomal recessive disease carrier screening in adults of reproductive age.The device is not intended for copy number variation, cytogenetic, or biochemical testing.
Physical State Multiplex microarray based detection system
Technical Method Microarray based method to detect genomic DNA mutations
Target Area human clinical specimens
Regulation Medical Specialty Immunology
Review Panel Pathology
Product Code PKB
Premarket Review Office of In Vitro Diagnostics and Radiological Health (OIR)
Submission Type 510(k)
Regulation Number 866.5940
Device Class 2
Total Product Life Cycle (TPLC) TPLC Product Code Report
Third Party Review Not Third Party Eligible
The above notice lists the category as "Device Class 2" and "Submission Type 510(k)", but FDA's other comments and letters to 23andMe indicate that perhaps at most, initial baseline 510(k) is needed - not updates for every variant. (Here).
Some of 23andMe's review paperwork under this classification is now appearing on the FDA website, here:
Device Classification Name Autosomal Recessive Carrier Screening Gene Mutation Detection SystemDe Novo Number DEN140044
Device Name 23ANDME PERSONAL GENOME SERVICE (HEREINAFTER KNOWN AS PGS)
23andMe - 1390 Shorebird Way - Mountain View, CA 94043 - Contact Kathy Hibbs
Regulation Number 866.5940
Classification Product Code PKB
Date Received 05/29/2014
Decision Date 02/19/2015
Decision Granted (DENG)
Classification Advisory Committee Immunology
Review Advisory Committee Clinical Chemistry