UPDATE - MONDAY - DECEMBER 18 2018
FDA HAS POSTED APPROVAL PDF's ON FMI CDX
See also all documents in one cloud zip file (Dec 18):
The Approval Order is 5pp; the Safety & Effectiveness document is 58pp; the Labeling is 43 pp.
Four conditions of approval include (1) "clinical concordance data to support the performance of your device within the appropriate clinical contexts." [?] (2) Response for NSCLC patients with EGFR T790M mutation mutant allele frequency (MAF) < 5%. (3) "Provide additional results from clinical samples to establish the analytical performance characteristics "for all variant types and genomic signatures." This includes MSI, TMB, CNA, rearrangements. (4) Software documentation for: validating and implementing software design changes.
The FDA specifically segregates "test output" or reporting into Category 1 CDx claims, Category 2 output of genes with "evidence of clinical significance," and Category 3 claims of "potential" clinical significance (the latter including e.g. animal studies or other rationales). See FDA explanation here. (510K gene panels have only Category 2&3 claims.)
The test runs on an Illumina HiSeq 4000. It uses paraffin block inputs and must have 55 ng of genomic DNA. The S&E documentation includes a "Table 5" which lists all FDA approved CDx (in any format, e.g. FISH) that parallels a CDx gene on the FMI label. Table 7 compares concordance of "F1 LDT" and "F1 CDX" (it's high.) There are many tables of comparisons to prior PMA tests (therascreen, cobas, etc). The product was not referred to an advisory panel "because the PMA substantially duplicates information previously reviewed by the panel." All statistics were based on "non inferiority testing."
Since the device was classified as a Breakthrough Device, the FDA's review expectations included "a balance of pre and post market data." The FDA concludes that because F1 CDX was "non inferior" to existing CDx tests, it "does not introduce additional risks." (Thus the reporting of Category 2 and 3 results, unavailable from prior single CDx's, were seen as not being germane to additional risks.) FDA concludes: "The probable benefits outweigh the risks." [Quotes from S&E document, P170019B.)
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FMI's own FMI CDX webpage is here.
The FDA specifically segregates "test output" or reporting into Category 1 CDx claims, Category 2 output of genes with "evidence of clinical significance," and Category 3 claims of "potential" clinical significance (the latter including e.g. animal studies or other rationales). See FDA explanation here. (510K gene panels have only Category 2&3 claims.)
The test runs on an Illumina HiSeq 4000. It uses paraffin block inputs and must have 55 ng of genomic DNA. The S&E documentation includes a "Table 5" which lists all FDA approved CDx (in any format, e.g. FISH) that parallels a CDx gene on the FMI label. Table 7 compares concordance of "F1 LDT" and "F1 CDX" (it's high.) There are many tables of comparisons to prior PMA tests (therascreen, cobas, etc). The product was not referred to an advisory panel "because the PMA substantially duplicates information previously reviewed by the panel." All statistics were based on "non inferiority testing."
Since the device was classified as a Breakthrough Device, the FDA's review expectations included "a balance of pre and post market data." The FDA concludes that because F1 CDX was "non inferior" to existing CDx tests, it "does not introduce additional risks." (Thus the reporting of Category 2 and 3 results, unavailable from prior single CDx's, were seen as not being germane to additional risks.) FDA concludes: "The probable benefits outweigh the risks." [Quotes from S&E document, P170019B.)
_____
FMI's own FMI CDX webpage is here.
