On April 6th, the U.S. Food and Drug Administration (FDA) continued to loosen the reins on the genetic diagnostic and DNA analysis company 23andMe with regarding to direct-to-consumer (DTC) genetic testing related to predicting disease risk. While falling short of permitting the company to provide risk analysis for disease likelihood in individuals per se, the agency granted permission to market its genetic diagnostic kits for a limited number of diseases according to an official announcement. The agency's actions suggest that it believes there is sufficient evidence that the risks to the public it perceived that motivated its earlier restrictions are not as likely as once thought.
The FDA's actions come on the heels of the agency's approval of DNA diagnostics for Bloom's Syndrome earlier this year (see "23andMe Receives FDA Approval for Genetic Diagnostic Test"). Readers may recall that the FDA effectively stopped 23andMe from selling its genetic analysis kit, which the company marketed as Personal Genomic Services (PGS) in November 2013 by issuing a Warning Letter to the Company (see "FDA Threatens Agency Action Against 23andMe Over Personal Genetic Testing"). According to the FDA, genetic diagnostics assays fall under the agency's purview and authority because they are medical devices (21 U.S.C. § 321(h)). According to its earlier letter, the testing service offered "is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body." At that time, the agency professed a desire to work with the company to assist in developing the type and quantity of evidence required for approval, but warned that it had spent "significant time" evaluating the PGS test and providing feedback to 23andMe. By complying with the agency by submitting the evidence for approval of a much more limited test, 23andMe was able to get the Bloom's Syndrome test approved.
This most recent approval is for ten genetic diseases as detected by 23andMe's at-home health-and-ancestry DNA testing kit (retailing at $199). The kit detects single nucleotide polymorphisms (SNPs) related to development of these ten diseases having a genetic component:
• Late-onset Alzheimer's – detecting the ε4 variant in the APO-E gene
• Parkinson's - the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene
• Celiac disease - a variant in the HLA-DQ2.5 haplotype
• Hereditary thrombophilia - Factor V Leiden variant in the F5 gene, and the Prothrombin G20210A variant in the F2 gene
• Alpha-1 Antitrypsin Deficiency - PI*Z and PI*S variants in the SERPINA1 gene
• Gaucher's disease type 1 - N370S, 84GG, and V394L variants in the GBA gene
• Early-onset primary dystonia - deltaE302/303 variant in the DYT1 gene,
• Factor XI deficiency - F283L, E117X, and IVS14+1G>A variants in the F11 gene,
• Glucose-6-phosphate dehydrogenase deficiency - Val68Met variant in the G6PD gene,
• Hereditary hemochromatosis - C282Y and H63D variants in the HFE gene
The agency did not grant approval for tests related to developing a disease in an individual, in particular for detecting disease-related variants of the BRCA1 or BRCA2 genes related to breast and ovarian cancer. Rather, the test results are predictive for the risk of inheritance of these genes by offspring, to be used inter alia to identify prospective parental pairs who both carry a disease-related allele and thus are at heightened risk for having a child with the disease.
FDA approval for genetic health risk reports were evaluated through the de novo classification pathway, a regulatory process for low-to-moderate-risk medical devices, the company said. In its approval, the FDA indicated it will create a class II exemption for 23andMe's substantially equivalent reports for other diseases and risk-predictive genes, provided that the company complies with agency requirements for establishing efficacy and safety. These actions open a pathway for the company to release additional genetic health risk reports, 23andMe also said in its announcement. "These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar [genetic health risk] tests," the FDA added. And the agency announced that it will outline a pathway for similar exemption for other DTC companies in the Federal Register.
These tests are much more limited in scope than 23andMe's original test, which included more than 250 "diseases and conditions" such as BRCA gene mutations, diabetes, coronary artery disease, an sensitivities to drugs such as warfarin, clopidigrel, and 5-fluorouracil. But the agency's approval, and avowed intention to permit 23andMe, and other companies, to market DTC genetic diagnostic tests suggest that the dawn of the age of personalized medicine has crept ever closer to breaking.
