Two statements by the FDA this week--one a letter to the DTC genomics company, 23andMe, the other a press release announcing the clearance of Illumina's MiSeq platform for a diagnostic assay--signal an agency on the move.
The most surprising part of Friday’s letter from the FDA to 23andMe was the neglect on 23andMe’s part to follow through on their own submissions to the FDA. Rather than putting forth any new doctrine, which I admit first went through my head when I read the headline today--that the FDA was finally mustering the will to issue guidance on LDTs, the letter reads quite boringly.
In Friday’s letter, it is stated:
“Since July of 2009, we have been diligently working to help you comply with regulatory requirements regarding safety and effectiveness and obtain marketing authorization for your PGS device. FDA has spent significant time evaluating the intended uses of the PGS to determine whether certain uses might be appropriately classified into class II, thus requiring only 510(k) clearance or de novo classification and not PMA approval, and we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification.”
So nothing new here. But the letter continues with some incrimination of 23andMe and what appears to be hubris on the part of the popular DNA testing service:
“Further, we provided ample detailed feedback to 23andMe regarding the types of data it needs to submit for the intended uses of the PGS. As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies. As discussed above, FDA is concerned about the public health consequences of inaccurate results from the PGS device; the main purpose of compliance with FDA’s regulatory requirements is to ensure that the tests work.”
Fourteen meetings and hundreds of emails. Was 23andMe gambling when they launched their big marketing campaign this year? Were they betting, as some guests on our program have concluded, that the FDA does not have the political will to regulate the genetic tests? The company’s strategy seems quite unclear, with one foot in regulation yet going on with business as usual, indeed ramping up business as usual with price incentives and an assertive marketing campaign.
So far, there has been no response from Anne Wojcicki and her team other than a brief statement by the press officer:
“We have not met the FDA’s expectations regarding timeline and communication regarding our submission. Our relationship with the FDA is extremely important to us, and we are committed to fully engaging with them to address their concerns.”
There's bound to be a backlash of opinion on Twitter and in the blogosphere, but so far there's not much. I looked for a response from three big fans of the DTC testing company. Daniel MacArthur offered nothing other than the headline everyone else was tweeting. John Wilbanks tweeted that he’s waiting for 23andMe to respond, and when they issued the short statement above, said he too is surprised by 23andMe's efforts, or lack thereof:
"@JohnWilbanks: Response from @23andme in the wild: they’ve been failing to respond on time. Bad FDA strategy. Surprised"
Dan Vorhaus (@genomicslawyer) only retweeted Fierce’s John Carroll’s headline.
"@JohnCFierce: Whoa, FDA gets mighty cross with 23andMe, tackles Ann Wojcicki. - Want to see what angry regulators look like?"
It's still early. 23andMe has become popular in the industry as the debate over regulation continues. But perhaps, and I say hopefully, the needle is moving.
23andMe’s Anne Wojcicki often talks about the fun side of her company’s product in her talks around the conference circuit: are your ancestors from where you think they’re from? how much Neanderthal do you have in you? does your urine smell like asparagus? and so on.
But the service offers more than just the “fun” information with their PGS, Personal Genome Service. In their letter, the FDA gets specific about the tests offered for healthcare decisions, such as the BRCA testing:
“For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist. Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment.”
Indeed, in an interview here, genetic counselor, Ellen Matloff related a sobering statement that she knew of women who had bought the BRCA tests (not particularly from 23andMe) and proceeded to undergo mastectomies when, indeed, it turns out the women didn’t need to. Matloff has been involved in genetic counseling at Yale since "before the book was written." She came right out and said that “DTC genomics were not accurate, protected, or helpful.”
Will this lead to more FDA action on LDTs in general?
As I mentioned above, one of my first thoughts on seeing the headline this morning was whether the FDA finally summoned the will to issue guidance on LDTs. For 23andMe is not the only company offering such tests. Myriad Genetics, who built a solid business on the BRCA testing, still has not gone the regulatory route on the popular breast cancer tests. Myriad’s sales have spiked sharply this year, part of what has been called the “Angelina Jolie effect”, an uptick in market awareness since the famous actress went public about her testing and mastectomies.
We’ve recently had to the program a couple guests who have made strong arguments for the FDA regulating these tests. Hank Greely is a law professor at Stanford who teaches a course on the FDA and has done a lot of work on regulation and bioethics. He says that regulation is necessary here and makes the case that the relation of regulation to business has a strong history in the US going back to the time of the railroads. He suggests that “carefully drawn regulation can be helpful to industry.”
And in an interview with Dan Hayes, an oncologist at the University of Michigan Cancer Cetner, we heard pretty much a plea with the FDA to buckle down and regulate diagnostics. Dan outlines the “vicious cycle” that the diagnostics industry finds itself in, leading to low prices and poor quality tests. One of the reasons for the vicious cycle is that the FDA hasn’t so far issued guidance on LDTs.
Dan asks that the industry grow up and look at diagnostic tests as they do therapeutics, and says that if we want to move forward then “the days of doing LDTs are past.”
In our interview with Liz Mansfield of the FDA a couple weeks ago, I chose not to spend much time going after her on the topic of LDTs. It’s been done and done. She did say that she and those working in the agency had a “tremendous amount of authority” to do their jobs. And she said that the FDA was already deep in the process of looking into new types of tests which have resulted from cheaper sequencing technology. Last week, the FDA announced the clearance of Illumina’s "next generation" MiSeq platform for a diagnostic assay, hailed by many, including NIH Director Francis Collins, as an important step forward for personalized medicine. It's also a demonstration of the FDA's ability to move forward with the new technologies appearing. But Liz also acknowledged there were times when they needed the go ahead from “higher forces”. LDT guidance “is wrapped up in some politics” she said, “and in that case FDA reviewers and managers don’t have a lot of authority. It’s really beyond our ability to say it’s ok to publish it.”
Perhaps we can look at the two correspondences from the FDA this past week, clearing the Illumina platform and slapping of 23andMe, together. One is a go ahead, the other a get-with-the-program or cease. Are we seeing a gradual incremental approach here, and if so, who will be next?