TWiV 651: FDA rules with Denise Esposito

August 9, 2020

Daniel Griffin provides a clinical report on COVID-19, then former FDA Chief of Staff to the Commissioner Denise Esposito joins us to explain the challenges in approving vaccines, antiviral drugs, and diagnostic tests during a pandemic, followed by answers to listener questions.

Hosts: Vincent Racaniello, Dickson DespommierAlan Dove, Rich Condit, and Brianne Barker

Guests: Daniel Griffin and Denise Esposito

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Download TWiV 651 (98 MB .mp3, 164 min)
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Intro music is by Ronald Jenkees

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9 comments on “TWiV 651: FDA rules with Denise Esposito

  1. Lisa Jones Aug 9, 2020

    I would like to ask the TWIV team to dedicate a show or portion thereof to a review of the Swedish approach and its pros and cons and trajectory. I think that this could be a helpful conversation, particularly if there is a significant delay in the execution of a successful vaccination campaign.

    Thank you. I am grateful for all your efforts.

  2. Hello TWiV team,
    Speaking of salty surfboard surfaces, please note the following study now underway at UEdinburgh. “Background: A recent pilot trial (small study to help design a larger one) indicated that hypertonic saline (salty water) nasal washout and gargling [12 times per day] reduces the duration of coronavirus upper respiratory tract infection by an average of two-and-a-half days. It was found that epithelial cells (cells on the surfaces of your body, such as your skin, organs and throat lining and inside your nose) can create an antiviral effect by producing hypochlorous acid (HOCl) from chloride ions (which are in salt). HOCl is the active ingredient in bleach. Epithelial cells therefore have this natural antiviral immune mechanism to clear viral infections. …”
    https://www.ed.ac.uk/usher/elvis-covid-19/about-the-study

    If I were 50 years younger I’d just leave my surfboard in the sun for twenty minutes 😉 Thanks for so many great shows, Jane

  3. David Lewis Aug 9, 2020

    Michael Mina addressed some of what was discussed in this TWiV, re his idea that cheap rapid result antigen tests should be deployed immediately to bring this pandemic to a halt, in a Q&A published on MedCram August 5.

    His thoughts appear to contradict some of what was said in this TWiV

    The Q&A is entitled: “How to Fix COVID-19 Testing Q/A with Dr. Michael Mina: Cheap, At Home, Rapid Antigen Tests”. It is at this link: https://www.youtube.com/watch?v=3seIAs-73G8

    Basically, Dr. Mina explained that as of August 5, the greatest barrier companies face as they decide whether to devote resources to trying to deploy what Dr. Mina is talking about, as of August 5, 2020, there is no legal way to do it,

    Dr. Mina: “The major thing unfortunately is regulatory. These are tests that live in this gray zone. They give results back to individuals, which by definition, if an individual is going to get a biometric result about their health that’s going to potentially cause them to change their behavior, that is more or less defined by CMS (Centers for Medicare and Medicaid Services) and CLIA (Clinical Laboratory Improvement Amendments) as a test that falls under CLIA which immediately puts it under FDA.

    The problem is the FDA is not a public health agency. They are an agency that is – one of their tasks is – to evaluate and approve diagnostic tests. So they literally don’t have a pathway to evaluate a test whose real major purpose is to reduce transmission of infections at a population level.

    The real issue is that until it gets clearly defined who is going to regulate it, no companies that have products that are potentially available are going to go and manufacture these in the millions. There’s no market because currently if they did the company would get shut down for illegal practices. I.e.,pumping out millions of tests that are not FDA approved. So the companies that could develop these tests right now won’t, for regulatory reasons”.

    Dr. Mina said he is encouraged by the groundswell he feels as a result of the TWiV coverage, his op-eds and preprints, and the work many others are doing to raise awareness, a groundswell that has resulted in Senators, Mayors, Governors, etc. getting in touch with him, but he appears to remain pessimistic as to what the immediate prospects are.

    Dr. Mina: “some of the people who are empowered to make these very big decisions about how to restructure this whole discussion, at least on the surface, we’re seeing the least amount of urgency from them. They’re kind of saying oh well this is you know submit your request or your application through this portal and and we’ll get back to you in three months or whatever it might be. That’s really extraordinarily frustrating.”

    Dr. Mina was asked well what about the new emergency use template the FDA issued July 29 that supposedly allows for companies to develop over-the-counter Covid-19 diagnostic tests that can be used outside of a lab? I.e. is this a positive move? I believe your guest Denise on TWiV 651 pointed to this as a solution to Dr. Mina’s problems. Mina doesn’t see it this way:

    Dr. Mina: “I think in some ways I would say it’s one step forward, and in a sort of a strange way a couple of steps backwards. The step forward is absolutely a good one. The FDA has clearly laid out that they are willing to have tests that can be performed at home and at offices and by individuals. But it doesn’t go far enough. They’ve put their cards down on the table now to show what they are expecting, and unfortunately, they are demanding that any at-home test needs to meet all of the same metrics and milestones as a solid laboratory based test.

    They still want the molecular sensitivity to be 90% of PCR. You’re not going to achieve this in a cheap daily rapid test. They also want every test to have a mechanism so that every negative and every positive test can be reported to the Department of Health.

    This means that all of these what could be one dollar paper strips need to be somehow linked to the internet or something along those lines for reporting. Every one of these companies that are developing at home tests will have to become a software company or have some other option for reporting. We can’t realistically create a a test for use at home and ensure that everyone is going to report their negative results every single day to the Department of Health – that’s just unlikely to happen. So there would have to be some sort of trigger built into the test, which is immediately is going to make it into a more expensive test.”

    Dr. Mina was asked, is the epidemiological community capable of making the philosophical reorientation that appears to be required to adopt the approach he is advocating?

    Dr. Mina: “I’ve been a little bit harsh on the FDA. I want to not be quite so harsh. The FDA was never given a mandate as far as I know to evaluate public health tools. Maybe its going to be CMS and CLIA that need to re-evaluate where these tests sit.

    I mean the short answer at the moment is no I don’t think that our current situation, our current infrastructure, is set up to have a philosophical repositioning. That said, I do think that… these things have gone a little bit viral… we’ve been really pushing it through op-eds and through scientific research to show that it can work. I think there’s beginning to become a groundswell of support. The message has gotten across to all levels of individuals who would potentially be making the big decisions.

    If there continues to be sort of political pressure and scientific pressure and public pressure, not to lower our bar and start to use an inferior diagnostic test, but to say we want a public health tool that can change the course of this epidemic and this is what it looks like. I think that it can change. It’s an uphill battle for sure.”

    Dr. Mina was asked who is producing these tests? What barriers to production do you see?

    Dr. Mina: “E25 Bio, [ a startup that Mina explained earlier has 3 entire employees ] maybe, could produce a a few million in a week or something, or they have manufacturers lined up that could potentially do that kind of thing and the prices could be very low. My imagination suggests to me that 3M is a huge company. We know that they are building a test and I presume that they would be able to make quite a lot of these as well.

    So there are some companies that could do it it’s just none of them are taking that next leap to actually start manufacturing them because there’s no legal route to do it.

    They don’t want to get shut down. Because there’s no legal route to do it there’s no purchasers so it’s a horrible catch-22” [ again, he refers to the regulatory and legal barrier he referred to right at the top of this MedCram Q&A ]

    Dr. Mina was asked, what about the 7 governors that have agreed to buy a lot of rapid result antigen tests, to have the tests, and to create a market for this type of test? Is that a positive development?

    Dr. Mina: “There’s a lot of confusion around this. When the EUA template came out everyone said hurrah you know the FDA is making the right choice and then just yesterday or I believe it was yesterday six governors of six states including Massachusetts, headed by Maryland I believe, came out with a pretty ambitious, relatively, proposal. They are going to band together and purchase three million of these Becton Dickinson & Company, or Quidel antigen tests, five hundred thousand per state, to put out into the community, but these all need a small machine. It’s one thing to buy five hundred thousand tests or three million tests but they all have to get processed on a little machine and it’s those machines that become limiting, and unfortunately these tests are true diagnostic tests so that makes them more expensive. And, they do have to report to the Department of Health because they are being regulated by CLIA.

    They’re not public health tools they’re diagnostic and so who can use the test is going to be limited. It’s going to be limited probably to people who are highly trained to use this particular instruments as simple as they are, and then the instruments themselves are going to be limited in terms of where they can be placed. And then because they are reimbursable by insurance companies that immediately inflates the sale price of each of these individual tests that are used for the instrument.

    This story is just a continuation of this effort to try to fit diagnostic tests which are a round peg into a square hole of public health testing. We just need to start to separate them and say these are different classes of tests. We don’t want to buy diagnostic tests for population level control of an infection, it’s just the wrong avenue. But the governors are looking forward and they’re saying well this is what we got now so that that’s what they’re going with.

    These Becton Dickinson and Quidel instruments, they’re good instruments, but they’re not the right ones for this purpose. From my understanding those are still highly sensitive I mean they got that FDA EUA, so the expense really gets driven up when you try to achieve that sensitivity”

  4. Gretchen Turner Aug 10, 2020

    One of the last letters talked about an old video (WW2? PSA?) titled, “Sneezes & Disease”. Do you have a link to that?

  5. Hi TWIVers,

    I am JAFERD (google it) living in Atlanta but working in Alabama. I propose that we change the reference to the Mina testing strategy as “Rapid point-of-spread testing (or if you don’t like the associated acronym, point-of-transmission testing) ” do decouple the diagnostic/treatment model that most physicians and possibly decision makers associate with the need for high sensitivity tests. It is a very strong association that I have found difficult to deprogram from colleagues that I have been attempting to convince of the exigency of this strategy.

    Keep up the great work. I listened to TWIV #640 on my last day of isolation (minimal symptoms, fortunately) and it almost made the previous days of wait and worry worth it.

  6. Jim Johnson Aug 10, 2020

    Hi Twivers. I somehow found Vincent’s Virology 2020 and that led me to TWIV. I have been listening since TWIV 598. As a mere Mathematician with no background in biologic things I still feel that I learn lot. While the details often go past me the culture is taking root.
    There has been so much talk about tests, but they all seem to be about ones developed in the US. I would be really interested in hearing some about what kinds of tests to other countries use. Do any of them have rapid tests that a pretty good at determining if one is capable of spreading the disease?
    I love the banter even if sometimes I have to groan about.
    For the record, I believe I had COViD at the end of March. I was sick for 17 days with many of the symptoms, but not sick enough to qualify for a test, i.e. I did not go the hospital. My doc agrees that I probably had it even though I now test negative for antibodies. Which brings me to the second question:
    Is it possible that the antibody test is sensitive to some antibodies but not others. So those of us who test negative may have antibodies, just not the ones the test looks for?
    Love the show. I’ve listened to some past episodes. Also IMMUNE, TWIP, TWIM. I did listen to one TWIP, but that seems aimed at people who know enough to diagnose parasitic diseases, and this certainly excludes me.
    Looking forward to the next episode.

  7. David Smith Aug 10, 2020

    Hi TWiV team
    I think the Rapid Tests Advocacy Facebook group needs the TWiV bump – share some of the many thousands of eyes you have 😉 https://www.facebook.com/Rapid-Tests-Advocacy-584120358946945/ They directly connect to RapidTests.org and there are some good publicity and meme ideas being shared there.

  8. Bill Hillebrenner Aug 11, 2020

    Hello TWIV, I am a retired BSME having worked on the “flight deck” (pilot station on the Boeing 747), on production of electronic components for printed circuit boards, with bankrupt AMSCO on a project to use vapor phase hydrogen peroxide as a sterilent. There our biological engineers grew colonies for our testing. I first learned of the VAST difference from a virus and “germ” in 1969. I found Virology Lecture #1 2020 VERY interesting and helpful. But it and other TWIV have told me the vast number of virus copies needed for an infectious dose. I have not heard what a cell burst load. But with the info presented makes me realize that there are thousands of viri in the air at all times. I am 75, never get vaccinated, am accused of never getting sick. I have been playing pickelball for the last two months with about 50 people in a large sports court building none wearing masks. In addition there are about 50 junior high girls playing volleyball in the other part of the building and another 50 older girls playing volleyball not wearing masks. We have NO known Covid cases. With your TWIV people talking of the need of 250,000 copies for infectious load. I read of your comments of “RNA fragments” found in quantity of 80 or 90. With 8000 people dying of all things every day and people dying WITH flu virus but not FROM the virus (CDC own statement that flu is not recorded) there is a lot of what appears convoluted info of the actual danger),

  9. Joanna Stull Aug 18, 2020

    HI Mass.gov websites states that travelers from lower risk states (as of this writing Aug 1, that is new England states NY and NJ) are free to come and go and do not have to fill out forms or quarantine.

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