Links - FDA recognizes CLINVAR; Issue is Sequencing Tests (even FDA) with off-site software

 AMA PLA codes are now not allowed if you have distributed inputs to testing (though this is allowed by CAP).

FDA allows use of outside databases for FDA approved sequence tests.

https://clinicalgenome.org/docs/fda-recognizes-clingen-assertions-in-clinvar-frequently-asked-questions/

https://www.fda.gov/media/119313/download

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A few years ago, FDA specifically allowed outside approved databases to be used in conjunction with FDA approved sequencing tests. (I don't remember if they were tests at 23andMe or if they were BRCAC tests getting FdA cleared by Myriad, or some other context.) Please find citations specific to Fda allowing outside databases as part of sequencing test approvals (or clearances.)

https://chatgpt.com/share/6941a0d2-47a0-8005-96ea-a5c772b1c263

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Here are FDA-primary citations showing FDA explicitly allowing “outside” (third-party) variant databases to be used to support FDA clearance/approval of sequencing / genetic tests—especially for clinical validity evidence in premarket submissions:

1. FDA final guidance (core policy hook): public variant databases can be used as valid scientific evidence in FDA review of NGS/genetic tests

• FDA guidance page (“Use of Public Human Genetic Variant Databases…”) states that publicly accessible variant databases can serve as sources of valid scientific evidence to support clinical validity in FDA’s regulatory review of NGS-based tests and other genetic/genomic tests. (U.S. Food and Drug Administration)

• In the guidance PDF, FDA explains that if databases follow the recommendations, their “data and assertions… would generally constitute valid scientific evidence… to support clinical validity” for FDA approval, and it describes the voluntary FDA recognition process for such databases. (U.S. Food and Drug Administration)

2. FDA “database recognition” program page (explicit permission language for sponsors): sponsors can use FDA-recognized database assertions in submissions

• FDA says recognition means FDA believes the database’s “data and assertions… can be considered valid scientific evidence,” and: “This program will allow sponsors to use the assertions within FDA-recognized databases to support the clinical validity of their tests.” (U.S. Food and Drug Administration)

• Same page also lists recognized databases (examples), including ClinGen (recognized 12/4/2018) and MSK OncoKB (recognized 10/7/2021). (U.S. Food and Drug Administration)

3. A concrete FDA recognition decision (ClinGen) stating FDA intends its assertions to be usable in future premarket submissions

• FDA’s ClinGen recognition decision summary concludes that ClinGen’s procedures provide reasonable assurance that its assertions “constitute valid scientific evidence” and “can be used to support clinical validity of genetic tests in future premarket submissions.” (U.S. Food and Drug Administration)

4. FDA press announcement reinforcing the policy (how test developers may rely on FDA-recognized public databases)

• FDA press announcement (Dec 4, 2018) explains FDA’s approach “clarifying how test developers may rely on clinical evidence provided in FDA-recognized public databases to support clinical claims for their tests” and help assure clinical validity. (U.S. Food and Drug Administration)

5. Federal Register notice for the guidance (useful for docketing / formal citation)

• Federal Register notice for the guidance describes publicly accessible databases as valid scientific evidence supporting clinical validity in FDA review of genetic/genomic tests. (Federal Register)

If you tell me which context you’re writing for (e.g., BRCA / hereditary risk like 23andMe, versus tumor/CDx somatic variants like OncoKB), I can point you to the most on-point recognized database + decision summary language for that specific use case.