Interview site: https://www.genomeweb.com/molecular-diagnostics/qa-regulatory-expert-karen-becker-provides-context-theranos-fda-interactions

Interesting Q&A. Thanks for sharing it. What’s even more interesting is what’s missing among these questions. We should be asking not just how credible are the answers but also how comprehensive are the questions.

There are two sets of public information currently available on Theranos, namely, WSJ’s Oct 15 (1), 16 (2), 2015 investigative pieces and other investigative media pieces it triggered, and the heavily redacted FDA Form 483s, released in response to FOIA requests (3, 4) so obvious questions ensue from information made available through them.

So, missing questions first.
CLIA-mandated proficiency tests (PTs): Why no questions relating to the most troubling aspect of the WSJ report, namely, several allegations from anonymous current and former employees that Theranos was allegedly cheating on its CLIA-mandated PTs, arguably the most important aspect of blood diagnostics? After all, if tests aren’t accurate, who cares if they are cheap and convenient? Given the enormity of the implications that ensue from PT cheating allegations, why no substantive discussion with a ‘well-regarded expert on regulatory matters‘, who claimed ‘she has no financial or other ties to Theranos‘, on the issue of PTs, their central importance in blood diagnostics, and the types of work-arounds that blood diagnostics labs could typically try to engineer, the implications of such efforts, etc.

Vacant senior lab positions: As anyone who has ever worked in a biology lab would know, be it in academia, R&D or clinical, things can go south in a matter of days when there isn’t clear leadership, guidance and oversight. Imagine then what could happen with no appropriately experienced and credentialed full-time lab director to guide a blood diagnostics company operating in an extremely complex and fast-changing regulatory landscape. Prominently reported issue of Theranos’ lab staffing issues include an Oct 23, 2015, Financial Times report (5) that since its last director resigned at the end of 2014, Theranos has no full-time lab director at its main lab, then located in Palo Alto, California, now located in Newark, NJ. This critical issue of missing senior level staff was also explored more fully in a Nov 6, 2015, WSJ follow-up report (6). That report added that, apart from the lab director, vacant positions include lab manager, manager of quality assurance and quality control and laboratory general supervisor, i.e., key senior lab staff. Since the original WSJ report (1) alleged bench scientists directly emailing the Theranos COO Balwani, seeking clarification on which PT tests to report, this Q&A missed a valuable opportunity to get insights from a regulatory expert on if and how a CLIA-credentialed blood diagnostics lab could maintain continuity, clarity, accuracy and precision when many key senior lab personnel positions are vacant. Other missed questions include,

  • Is it normal for a CLIA-accredited blood diagnostics lab innovating new Lab Developed Tests (LDTs) to have so many simultaneous senior level lab staff vacancies?
  • Is it possible for a CLIA-accredited blood diagnostics lab with so many simultaneous senior level lab staff vacancies
    • To generate the rigorously controlled, high quality data necessary to pass muster with the FDA?
    • To maintain rigorous quality assurance and control, necessary for maintaining CLIA accreditation?

Now for some problematic answers.
Q: ‘They got 510(k) clearance for the HSV-1 test, which FDA deemed to be substantially equivalent to a predicate device: Focus Diagnostics’ HerpeSelect1 and 2 Immunoblot IgG. FDA’s posted documents described Theranos’ test as a chemiluminescent immunoassay, which is not a novel technology. But then, as you note, the FDA documents also refer to this Theranos system, which the company claims is proprietary and novel. So, why wouldn’t Theranos have to get a de novo 510(k) clearance instead of a 510(k)?
A: …’I think the most novel aspect of Theranos as a company is their business model. I think that’s what sparks a lot of interest in them, as well as some questions and concerns in the diagnostic industry. For one thing, Theranos is posting its test prices online and they charge the same amount for their tests to anyone that asks versus the big labs that have pricing schemes based on who the customer is. They’re not posting their prices online [like Theranos], and plus, Theranos prices are less. That’s one example of how the business model is novel. And the technology I would say is a more incremental innovation‘.

This last bit of the answer is completely outside of the purview of the question. Ok for a regulatory expert to opine on regulatory matters. Why bring up their business model and prices, especially when they weren’t even part of the question? In any case, bringing up of their business model merited logical follow-up about how such a model could be sustained in the blood diagnostics industry where margins are already in the single digits according to Bryan Roberts, a venture capitalist well-versed in healthcare start-ups (7). As for the cheaper prices, Theranos test prices are clearly unsustainable, even more so given that they aren’t re-imbursable through health insurance. Clearly, Theranos is burning through investor money by offering blood tests too cheaply, betting on increasing them later once they estimate they’ve established sufficient market presence. As well, tests prices are irrelevant in the face of the much more important issue of test accuracy, which wasn’t even part of this Q&A, a most glaring oversight on the part of the questioner.

Q: ‘You don’t have any financial relationship with the company. But if Theranos had been one of your clients, is there any area that you think they could have done better or differently in dealing with the FDA?
A:…’I think Theranos hasn’t gotten enough credit for being proactive. Even though they didn’t need to, they went to the agency voluntarily a few years ago with the expressed goal of getting all their LDTs cleared by the FDA‘.

Q: ‘Theranos maintains it has been transparent. Do you think they have been?
A: ‘I think they have been transparent in that even though they didn’t need to, they went to the FDA to begin the process of getting all their tests cleared. They’ve even come out in favor of FDA’s LDT regulation even though most of the clinical labs have not.

These highlighted answers are quite problematic since Theranos became well known for its unprecedented lack of transparency from the beginning. First, how could the respondent possibly know that Theranos ‘went to the agency voluntarily a few years ago with the expressed goal of getting all their LDTs cleared by the FDA’ when it was famously in ‘stealth mode’ until well into 2013. As far as I can tell, independently corroborated information as to when Theranos first went to the FDA for approval of its LDTs isn’t part of publicly available knowledge.

Second, there is no indication that Theranos is behaving differently in any way, shape or form to other labs that have LDTs. As I’ve pointed out in some of my other Theranos-related answers, increasingly over the past few years LDTs came to occupy a grey area. Overseen by CMS, CLIA was enacted in 1988, and is clearly inadequate for regulatory oversight of LDTs. Recognizing this, the FDA published a draft guideline on Oct 4, 2014, well before news of Theranos’ alleged infractions ever came to public notice. Those guidelines were FDA’s shot across the bow for LDTs in general, meant to notify US blood diagnostics labs, Theranos included, that their LDTs were likely to come under FDA purview, unless and until Congress enacts laws updating the 1988 CLIA, which hasn’t happened yet. So the notion of Theranos going above and beyond to get their tests cleared by the FDA is disingenuous to say the least. In fact, doing so is merely what’s minimally required of them in a fast-changing regulatory landscape.

Where her answers pass muster for me: FDA inspection related issues, at least her interpretation of the two Form 483s made publicly available thus far.


  1. The Wall Street Journal, John Carreyrou, Oct 15, 2015. Hot Startup Theranos Has Struggled With Its Blood-Test Technology
  2. The Wall Street Journal, John Carreyrou, Oct 16, 2015.Hot Startup Theranos Dials Back Lab Tests at FDA’s Behest
  3. FDA’s Theranos inspection, Mary R. Hole, Yung W. Chan, Stayce E. Beck, Aug 25 to Sep 16, 2015. Page on fda.gov
  4. FDA’s Theranos inspection, Seema S. Singh, Ian A. Pilcher, Aug 25 to Sep 16, 2015. Page on fda.gov
  5. The Financial Times, David Crow and Adam Samson, Friday, Oct 23, 2015. Theranos blood labs under fresh scrutiny
  6. The Wall Street Journal, John Carreyrou, Nov 5, 2015. Theranos Searches for Director to Oversee Laboratory
  7. The New York Times, Katie Benner, Nov 5, 2015. Why Health Care Start-Ups Like Theranos Need Investing Expertise