8 ms·

This seems absolutely reasonable. The letter indicates that the FDA has notified 23andMe that their products are not satisfactorily cleared, they're reached out

by jfasi 13y ago

This seems absolutely reasonable. The letter indicates that the FDA has notified 23andMe that their products are not satisfactorily cleared, they're reached out to them several times, and they've offered assistance through a group they specifically set up to help companies in this situation. Meanwhile, 23andMe went ahead and began marketing and selling their product, despite the FDA's concerns. Relevant quotes: > Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions. > However, to date, your company has failed to address the issues described during previous interactions with the Agency or provide the additional information identified in our September 13, 2012 letter for (b)(4) and in our November 20, 2012 letter > To date, 23andMe has failed to provide adequate information to support a determination that the PGS is substantially equivalent to a legally marketed predicate for any of the uses for which you are marketing it; ... > ...we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification. > 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... > Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS.

tptacek 13y ago
Moreover, it appears from the letter that the concerns are about marketing; ie, presumably the FDA was simply asking for 23AM to clarify their copy to remove any implication that you could use the product as a substitute for a doctor's assessment of your e.g. cancer risk.
- icegreentea 13y ago
  It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission. The claims by the FDA directly tie into the original claims by 23andMe as their intended use. In any case, the FDA right now doesn't just want a change of copy. By "cease marketing", I presume they don't mean advertise it differently, they mean stop offering the product to customers - period. While the FDA certainly appears to be taking issue with the specific marketing copy, they seem to be more annoyed that 23andMe has basically failed to complete the regulatory submission process - amongst other things failing to provide evidence to the FDA that their product actually works as intended.
  - mbreese 13y ago
    > It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission Well, you don't get this far into trouble with a regulatory agency without having a contact within the agency that you are working with. So, I'm fairly certain that 23andMe probably knows what the FDA wants, but they might disagree. I'll be disappointed in the company if they have ignored the FDA all these years when it was obvious that they'd need to have some sort of approval (even if it was an FDA acknowledgement that they didn't fall under regulation). What I really want to know is what 23andMe's response to the FDA will be. They must have known this was coming and should have a press release today.
  - tptacek 13y ago
    "[...] we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification [...]". Incidentally, the FDA is lagging a lot of other criticism and restrictions on the 23AM service; for instance, you can't even buy the service in Maryland, which forbids any home lab testing for health conditions not administered by licensed professionals. Similarly, there have been many critiques in the media and elsewhere about the lack of rigor in the 23AM analysis, relative to the importance of some of the conditions the service is implicated in.
jxf 13y ago
If you look at the FDA's website, it's littered with dozens of communications begging 23andme to submit some documentation about their product so that the FDA can evaluate the medical claims they're making. See, e.g., this one from June 10, 2010: [0] http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/Industry/UCM215240.pdf http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/... All the FDA wants in this letter is some kind of understanding that their genetic tests are actually valid and correct, since they are making medical claims regarding their accuracy: > 23andMe has never submitted information on the analytical or clinical validity of its tests to FDA for clearance or approval. However, your website states that the 23andMe Personal Genome Service™ is intended to tell patients in advance how they will respond to certain medications including warfarin and clopidogrel. It also states that the data generated from the 23andMe Odds Calculator, a feature ofthe 23andMe Personal Genome Service™, includes the contribution of single-nucleotide polymorphisms (SNPs) to disease risk. Consumers may make medical decisions in reliance on this information. The FDA then establishes its ability to regulate this (remember, it's legally required to do this): > During a meeting between 23andMe and FDA on July 29, 2009, you described the 23andMe Personal Genome Service™ as consisting of a software program that analyzes genetic test results that are generated by an external laboratory in order to generate a patient specific test report. Thus, the 23andMe Personal Genome Service™ is a diagnostic device and subject to all applicable requirements of the Act. They then very helpfully point them to all the forms, documents, etc., necessary to satisfy the legal requirements: > For a device requiring premarket approval, the notification required by section 510(k)of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). There's even a helpful mailing address and fax number: > Please direct your questions and response to: James L. Woods, Food and Drug Administration, 10903 New Hampshire Avenue, W066-5688, Silver Spring, MD 20993 Honestly, this sounds like 23andme has been getting away with something for a while and the FDA is tired of giving them leeway.
- tptacek 13y ago
  The bio on the guy who sent the letter you linked is interesting; not the "career civil servant maybe with a JD" you'd expect from an enforcement action: http://oba.od.nih.gov/oba/sacghs/roster/bio/2010/Alberto%20Gutierrez.pdf http://oba.od.nih.gov/oba/sacghs/roster/bio/2010/Alberto%20G...
dnautics 13y ago
Not all of it is reasonable, at all: "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" Uh, you don't think the surgeon is going to demand a second BRCA test be done before performing the surgery?
- mbreese 13y ago
  The point isn't necessarily the second test (which would have to be done). It's also the emotional distress caused by a potential false positive, which could be severe. You could imagine in an extreme case some one finding a result with a poor prognosis and deciding to commit suicide. Now, if that result was a false positive, you can see where you'd want to have some assurances that their test was accurate. This is an extreme example, and I have no knowledge that it ever happened, but it is possible. This might not even require a technical fix with the test, but rather a marketing and reporting of results.
  - unclebucknasty 13y ago
    From what I understand, the test doesn't attempt to diagnose an existing condition. Instead, it shows whether you have a gene that indicates a predisposition to the condition. In that case, prophylactic measures can be taken, once confirmed and if desired. This is what drove Angelina Jolie's decision to have a double-mastectomy. That's a hugely significant difference vs. actually being diagnosed with a life-threatening condition. I don't think people would commit suicide or become unduly despondent if they learned they have a gene. They would just know they need to take action, get further testing, be vigilant, etc. It's not much different (in spirit) from knowing that your family history predisposes you to a certain condition.
    - mbreese 13y ago
      It's all about education and results reporting. Where you or I might see a result as a predisposition to a phenotype with a statistical probability, someone else might see a death sentence. That could be one area that the FDA might be trying to address.
judk 13y ago
What does "predicate" mean in this context?
- nknighthb 13y ago
  As far as I can tell, you could translate that as "existing product". Given A and B, if A is already legally marketed, and B is basically the same thing, B has a lower bar to clear. Googling for "legally marketed predicate" turns up results like a 501(k) for a catheter[1] that the manufacturer says is "substantially equivalent" to another catheter already on the market. [1] http://www.accessdata.fda.gov/cdrh_docs/pdf/K963092.pdf http://www.accessdata.fda.gov/cdrh_docs/pdf/K963092.pdf
- ska 13y ago
  (expanding a little on nknighthb's comments): The primary path to approval to market for a new device or drug is the PMA (pre market approval). This is fairly extensive an costly for the company (e.g. clinical trials). A 510(k) filing allows you to take a short cut by identifying a "predicate device" that is "substantially equivalent". In other words you are saying "we do the same as X but we [also do Y/do this differently/etc.]". At least, you are claiming this for the scope of your "indications for use" (which are the only uses you can market your device for). This doesn't let you off the hook entirely at all. You still need to demonstrate safety and efficacy, perform risk analysis, follow standard manufacturing and product development methodologies (e.g. ISO13485, IEC60601, etc. ), but it is a lot faster and less involved than a PMA. If you don't use one of these accelerated paths, you'll need a PMA before you can market your product in the US. The key issue here is that 23andme has filed one or more 510(k)'s, but have failed to support them properly.
Ssanders 13y ago
The info that the company had lots of notice and apparently didn't do anything is very crucial to understanding this. Thanks for the info.

by jfasi 13y ago

tptacek 13y ago

Moreover, it appears from the letter that the concerns are about marketing; ie, presumably the FDA was simply asking for 23AM to clarify their copy to remove any implication that you could use the product as a substitute for a doctor's assessment of your e.g. cancer risk.

icegreentea 13y ago
It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission. The claims by the FDA directly tie into the original claims by 23andMe as their intended use. In any case, the FDA right now doesn't just want a change of copy. By "cease marketing", I presume they don't mean advertise it differently, they mean stop offering the product to customers - period. While the FDA certainly appears to be taking issue with the specific marketing copy, they seem to be more annoyed that 23andMe has basically failed to complete the regulatory submission process - amongst other things failing to provide evidence to the FDA that their product actually works as intended.
- mbreese 13y ago
  > It's actually kind of hard to tell -exactly- what the FDA wants without reading the original 510(k) submission Well, you don't get this far into trouble with a regulatory agency without having a contact within the agency that you are working with. So, I'm fairly certain that 23andMe probably knows what the FDA wants, but they might disagree. I'll be disappointed in the company if they have ignored the FDA all these years when it was obvious that they'd need to have some sort of approval (even if it was an FDA acknowledgement that they didn't fall under regulation). What I really want to know is what 23andMe's response to the FDA will be. They must have known this was coming and should have a press release today.
- tptacek 13y ago
  "[...] we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification [...]". Incidentally, the FDA is lagging a lot of other criticism and restrictions on the 23AM service; for instance, you can't even buy the service in Maryland, which forbids any home lab testing for health conditions not administered by licensed professionals. Similarly, there have been many critiques in the media and elsewhere about the lack of rigor in the 23AM analysis, relative to the importance of some of the conditions the service is implicated in.

jxf 13y ago

If you look at the FDA's website, it's littered with dozens of communications begging 23andme to submit some documentation about their product so that the FDA can evaluate the medical claims they're making. See, e.g., this one from June 10, 2010: [0] http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/Industry/UCM215240.pdf http://www.fda.gov/downloads/MedicalDevices/ResourcesforYou/... All the FDA wants in this letter is some kind of understanding that their genetic tests are actually valid and correct, since they are making medical claims regarding their accuracy: > 23andMe has never submitted information on the analytical or clinical validity of its tests to FDA for clearance or approval. However, your website states that the 23andMe Personal Genome Service™ is intended to tell patients in advance how they will respond to certain medications including warfarin and clopidogrel. It also states that the data generated from the 23andMe Odds Calculator, a feature ofthe 23andMe Personal Genome Service™, includes the contribution of single-nucleotide polymorphisms (SNPs) to disease risk. Consumers may make medical decisions in reliance on this information. The FDA then establishes its ability to regulate this (remember, it's legally required to do this): > During a meeting between 23andMe and FDA on July 29, 2009, you described the 23andMe Personal Genome Service™ as consisting of a software program that analyzes genetic test results that are generated by an external laboratory in order to generate a patient specific test report. Thus, the 23andMe Personal Genome Service™ is a diagnostic device and subject to all applicable requirements of the Act. They then very helpfully point them to all the forms, documents, etc., necessary to satisfy the legal requirements: > For a device requiring premarket approval, the notification required by section 510(k)of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). There's even a helpful mailing address and fax number: > Please direct your questions and response to: James L. Woods, Food and Drug Administration, 10903 New Hampshire Avenue, W066-5688, Silver Spring, MD 20993 Honestly, this sounds like 23andme has been getting away with something for a while and the FDA is tired of giving them leeway.

tptacek 13y ago
The bio on the guy who sent the letter you linked is interesting; not the "career civil servant maybe with a JD" you'd expect from an enforcement action: http://oba.od.nih.gov/oba/sacghs/roster/bio/2010/Alberto%20Gutierrez.pdf http://oba.od.nih.gov/oba/sacghs/roster/bio/2010/Alberto%20G...

dnautics 13y ago

Not all of it is reasonable, at all: "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" Uh, you don't think the surgeon is going to demand a second BRCA test be done before performing the surgery?

mbreese 13y ago
The point isn't necessarily the second test (which would have to be done). It's also the emotional distress caused by a potential false positive, which could be severe. You could imagine in an extreme case some one finding a result with a poor prognosis and deciding to commit suicide. Now, if that result was a false positive, you can see where you'd want to have some assurances that their test was accurate. This is an extreme example, and I have no knowledge that it ever happened, but it is possible. This might not even require a technical fix with the test, but rather a marketing and reporting of results.
- unclebucknasty 13y ago
  From what I understand, the test doesn't attempt to diagnose an existing condition. Instead, it shows whether you have a gene that indicates a predisposition to the condition. In that case, prophylactic measures can be taken, once confirmed and if desired. This is what drove Angelina Jolie's decision to have a double-mastectomy. That's a hugely significant difference vs. actually being diagnosed with a life-threatening condition. I don't think people would commit suicide or become unduly despondent if they learned they have a gene. They would just know they need to take action, get further testing, be vigilant, etc. It's not much different (in spirit) from knowing that your family history predisposes you to a certain condition.
  - mbreese 13y ago
    It's all about education and results reporting. Where you or I might see a result as a predisposition to a phenotype with a statistical probability, someone else might see a death sentence. That could be one area that the FDA might be trying to address.

judk 13y ago

What does "predicate" mean in this context?

nknighthb 13y ago
As far as I can tell, you could translate that as "existing product". Given A and B, if A is already legally marketed, and B is basically the same thing, B has a lower bar to clear. Googling for "legally marketed predicate" turns up results like a 501(k) for a catheter[1] that the manufacturer says is "substantially equivalent" to another catheter already on the market. [1] http://www.accessdata.fda.gov/cdrh_docs/pdf/K963092.pdf http://www.accessdata.fda.gov/cdrh_docs/pdf/K963092.pdf
ska 13y ago
(expanding a little on nknighthb's comments): The primary path to approval to market for a new device or drug is the PMA (pre market approval). This is fairly extensive an costly for the company (e.g. clinical trials). A 510(k) filing allows you to take a short cut by identifying a "predicate device" that is "substantially equivalent". In other words you are saying "we do the same as X but we [also do Y/do this differently/etc.]". At least, you are claiming this for the scope of your "indications for use" (which are the only uses you can market your device for). This doesn't let you off the hook entirely at all. You still need to demonstrate safety and efficacy, perform risk analysis, follow standard manufacturing and product development methodologies (e.g. ISO13485, IEC60601, etc. ), but it is a lot faster and less involved than a PMA. If you don't use one of these accelerated paths, you'll need a PMA before you can market your product in the US. The key issue here is that 23andme has filed one or more 510(k)'s, but have failed to support them properly.

Ssanders 13y ago

The info that the company had lots of notice and apparently didn't do anything is very crucial to understanding this. Thanks for the info.