A red letter day for consumer genomicsPosted: November 27, 2013
The news that FDA has written a stiffly-worded warning letter to 23andme signals a new milestone in the long and winding road to a coherent regulatory framework for consumer genomics. I was just finishing a gruelling slog to submit a paper when I got an email alerting me to this bombshell and have spent the time since en route to Montreal, so I am not up-to-date with reaction on the internet (although I have read Myraqa’s excellent post).
It is now over a year since 23andme submitted a de novo 510k submission to FDA and things have been very quiet since then. FDA’s letter makes plain that behind the scenes things have not been going well between the company and the agency. I have read quite a few FDA warning letters in the course of my research over the last few years but I have never seen one this stern before. The FDA are indicating an extreme displeasure with 23andme’s failure to meet their regulatory requirements. So where did it all go wrong and why has a letter been sent now? I have spoken to neither 23andme nor the FDA but here is my take on what has happened.
I think to understand this we need to go back to the FDA’s advisory committee meeting on consumer genomics, held in March 2011. I was invited to that meeting to give an overview on the regulatory trends across the globe, so had a ringside seat at this particular fight. Much of the subsequent internet discussion of the meeting focused on the panel’s view that most genetic tests should be offered through a physician. But in my opinion that was not the real meat of the meeting. The substance of the discussion was about science, not ethics. From that perspective the highlights of the meeting included a testy exchange between the panel and deCODE’s Jeff Gulcher on statistical issues such as the importance of pre-test probability, and the FDA’s presentation on the statistical challenges of validating polygenic genetic risk assessment (which was given by the scarily brainy Marina Kondratovich).
The critical question the FDA asked the panel was whether this class of tests should be held to the FDA’s statutory standard i.e. should be able to provide “clinically significant results”. Unsurprisingly the panel was not willing to operate a policy of genetic exceptionalism for consumer genomics companies and affirmed that this standard should be applied. But genetic exceptionalism was precisely what 23andme were asking for at the meeting: they suggested that FDA needed to redefine clinical validity to deal with their type class of tests. The FDA’s new warning letter suggests that much of the tension between company and agency is at this sticking point.
23andme have had a fair measure of success in challenging the status quo. I believe that they, along with their erstwhile competitors decode and Navigenics, have shifted the terrain on which we debate the merits of genetic risk prediction, largely by reframing the issue as one of consumer rights. But that ideological victory is of little import when it comes to the question of what constitutes adequate validation for their tests. That was an issue on which the three companies could not even agree amongst themselves when they undertook their industry standard-setting initative. It should be no surprise then that this remains 23andme’s Achilles heel.
But why did they FDA’s letter come now? Only the agency can answer that question, but I think that the tipping point would have been the launch of 23andme’s national consumer advertising campaign. We should remember that the last spate of FDA action in this sector was prompted when Pathway Genomics began to sell its tests through Walgreens, a high-street pharmacy chain. Advertising your tests on the television when you have applied for, but are struggling to gain, FDA approval is not a smart tactic. It is a move, I would suggest, born of desperation, rather than stupidity. The company must have known they were likely to raise regulators’ hackles but they are in desperate search for a milestone which would convince outsiders that they are achieving some measure of success (even if they are still a long way from profit).
Perhaps they thought that since the FDA have still not received the green light from the Obama administration to issue their draft guidance on the regulation of laboratory-developed tests, then they had some political wiggle room. Clearly that was a mistake. Historically the FDA has often developed new policy through a bottom-up process of individual actions, and that is how the LDT issue is currently being played out – witness the agency’s recent action against Atossa Genetics (and see the Myraqa blog for a great post on that story). FDA are to be applauded for sticking to their scientific guns. Let us hope that the draft LDT guidance follows soon.