tinalexander.github.io / notes / 2023 / 04 /
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Our priority remains providing the information necessary to protect the nation’s public health. With the end of the public health emergency, CDC will no longer get the same data. We are working to update the measure used to convey the risk of COVID-19 in communities based on data that will be available. CDC will provide additional information on the updated measure before the PHE declaration expires.
CDC has not yet received any samples from American Samoa, but will support confirmatory testing and additional lab testing as needed.
JESSICA PENNEY, CDC [01:03:40]
On October 14th, 2022, the Southern Nevada Health District was contacted by a local provider serving as a sole pediatric neurosurgeon for Clark County, Nevada, who noted a higher number than expected of children impacted by intracranial abscesses at their hospital.
The report came as a provider noted two patients diagnosed that month. Overall, they identified 14 patients at their institution since 2022 had began.
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JESSICA PENNEY, CDC [01:06:25]
In phone interviews, 64% of parents or guardians reported that their child had cold symptoms prior to hospitalization. 79% of caregivers sought care for their child prior to hospitalization, most often at an emergency department. And there was a 38% decrease in mask use in schools after the mask mandate was lifted in Nevada.
The cause of the increased number of cases in 2022 was not clear, but potentially the increased number of cases might be due to changing respiratory viral patterns. This figure shows the number of cases in blue by month during that year. Cases peaked in summer and fall and all occurred after March.
The indoor mask mandate, which included schools, was lifted in Nevada on 2/10/2022, although as I mentioned previously, the majority of the affected individuals in this population had continued to wear masks even after the mask mandate was lifted.
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JESSICA PENNEY, CDC [01:08:54]
So in terms of the mechanisms for infection, so in pediatric infections that involve intracranial infections, most often these are spread from contiguous infections, often sinus or ear infections that are partially treated that extend inwards and do potentially cross the blood brain barrier. They are more commonly seen in our pediatric patients with these contiguous infections as the primary cause.
In terms of symptoms, they can initially be very subtle for those presenting, which is sometimes why there is a little bit of a delay in diagnosis. The classic symptoms are fevers, headache, and then later on, as there’s the effect on the brain, focal neurologic deficits.
Seizures were rare in the population that we saw, but most were presenting with focal neurologic deficits by the time of diagnosis.
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JESSICA PENNEY, CDC [01:10:20]
So the median age for those affected, at least in 2022, was 12 years old from in Clark County. Historically, these abscesses are seen more often in younger age groups. I think 8 to 10 was what I saw in the literature. But again, we’re affected by very small numbers, but it’s something we’re going to continue watching this year to see what happens with the trends in our county.
And hopefully by sharing this information, other health departments can look into things as well and see if it’s happening in other places.
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JESSICA PENNEY, CDC [01:11:39]
So we’ve been working very closely with the community provider who reported this initial concern to us, who had heard anecdotal evidence from other providers such as herself who are seeing this in other parts of the country.
We did put out the health release and we’re currently working on publishing something in the MMWR. So this is more widely released to the community, again, to raise awareness about something that might be going on in other places.
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ZACH WARD, NORTH CAROLINA [01:12:10]
Did you also see increases– I know a lot of us have seen increases in invasive group A strep in kids and long term care facilities, etc. Were you seeing those same sort of things coincident with this increase in intracranial infections?
JESSICA PENNEY, CDC [01:12:26]
So I have not been able to do a deep dive into that. But at least talking with our disease investigation and surveillance staff, we had not seen the similar trend in our population, because I was suspecting that we might be seeing that happening concurrently as well. But it is something we are looking further into.
[00:03:24] To date, there are two confirmed measles cases in the territory. Director of health, clinical director, Dr. Elizabeth Lauvao, told KVZK the latest confirmed case is a four year old male student.
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[00:04:33] He is a student at Kanana Fou Elemetnary, the same school attended by the eight year old female student confirmed as the first measles case.
The confirmation by the department of health came from lab results of samples that arrived on Monday night from the lab in Hawaii.
Dr. Lauvao said a total of 39 samples were sent for testing, and 26 came back negative, while one was positive for measles.
NATALIE THORNBURG, CDC [00:14:06]
So if you recall from earlier in the pandemic, we were talking about variants like Alpha, Delta and Omicron. Omicron emerged late in fall 2021, and all current circulating lineages are Omicron variants of virus. The Omicron lineage and lineages have accumulated substitutions in the spike over time.
So that Omicron emergence happened with many, many changes in the spike protein. It was about 30 amino acid changes, across the full spike protein, or 15 substitutions, in the receptor binding domain. And that’s the part of the spike protein that binds to the cellular receptor ACE2.
We have not observed a dramatic shift in spike since that Delta to Omicron variant shift, but we have continued to see accumulating substitutions in the spike protein more incrementally over time, and that can be described as drift, which happens more slowly.
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NATALIE THORNBURG, CDC [00:18:46]
So what we’re looking at now from XBB to XBB.1.5 are just two substitutions. There are two XBB.1.9 lineages currently on the data tracker that are increasing in proportion listed there, 9.1 and 9.2. Those two, even though they evolved independently of XBB.1.5, have identical spike sequences in comparison to XBB.1.5 and that is demonstration of convergent evolution, where you have independent evolution that leads you to the same place.
XBB.1.16, which has been causing an increase in cases in some international locations, and is currently increasing in proportion in the United States, has two additional substitutions relative to XBB.1.5 and one is in the N terminal domain, which can be the target for some weakly neutralizing antibody, but not the primary target for neutralizing antibodies, and then one in the receptor binding domain, which is the primary target of neutralizing antibodies.
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NATALIE THORNBURG, CDC [00:24:41]
I just wanted to remind you that we’ve seen several surges of infection. It has not fallen into an exact seasonal pattern yet, but over the past few years, we have seen a late-summer-early-fall surge, or mid-summer-early-fall surge, and then another surge over the holidays. Our biggest one really being that Delta to the first Omicron shift.
And we’ve been decreasing in cases since early January. And we sit above 5% test positivity.
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PETER MARKS, FDA [00:01:04]
I think it’s been easy with all of the noise around mRNA vaccines to forget that protein based vaccines represent a very important part of our armamentarium for vaccination. And spoiler alert, I’m happy to say that I don’t view any one vaccine technology as the be all and end all. I think that mRNA vaccines are great, viral vector vaccines are great, and protein based vaccines are very, very important.
And in fact, the potential flexibility that we could have in the ability to generate vaccines rapidly with protein based vaccines, I don’t believe, has been fully exploited. And I think today is a chance for us to talk about that relative to COVID 19, but also may have implications for the larger field of using proteins for vaccination. And so I’m really looking forward to a thorough discussion today.
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PETER MARKS, FDA [00:02:48]
I think that if we address some of those issues, we might have a another series of vaccines in our armamentarium that could be made as quickly as, for instance, mRNA based technologies, that might be as or more acceptable to certain parts of the population.
But even more important, that might be applicable to other infectious disease may come in the future. Because, again, I don’t believe that there’s one size fits all for vaccines and pathogens, and there may be some pathogens that come our way where protein based vaccines will be key in addressing them.
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ROBERT JOHNSON, BARDA [00:06:51]
With the COVID 19 mRNA based vaccines, we can have a strain selection cycle that is much shorter. And this is incredibly important, as the later in the year you can make the strain selection decision, the shorter the time between decision and start of vaccination, and therefore the more likely that the vaccine will match the circulating strain.
This causes a challenge for recombinant protein vaccines to pivot as quickly as the mRNA vaccine can. And this is the issue and the challenge that we are looking to solve. So the decision isn’t to move it, and adjust the decision date. You know, maybe that’s potentially, for some, an option on the table. But from the BARDA perspective, really not the direction we’re looking to go.
What we’re really interested in is the solution which involves accelerating the manufacturing process so that they can meet this shorter production timeline that we see with mRNA.
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ROBERT JOHNSON, BARDA [00:07:53]
We know this is an incredibly hard issue, and that’s why we’ve brought together some of the leading experts in the field who have been working this problem, not just in the context of COVID 19 vaccines, but well before. And that’s really the key for this workshop. We’re not here to talk about a particular COVID vaccine.
We’re here to talk about approaches, challenges and potential solutions to expedite strain change with different recombinant protein based platforms. This can include items such as manufacturers taking a little bit of additional risk earlier on in the process, or incorporating new technologies, such as better expression systems or ways to make seed banks faster.
This effort to expedite strain change capability, and the overall development process for recombinant vaccines, is critical to retain recombinant based COVID 19 vaccines as viable options, which closely aligns with BARDA preparedness and response interests.
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ROBERT JOHNSON, BARDA [00:10:10]
So Project NextGen is, as has been indicated before, really focused on the next generation of vaccines and therapeutics. How do we improve on our current products?
So such things as mucosal vaccines, particularly intranasal and other approaches that may have an ability to improve transmission blocking capabilities, vaccines that provide a broader or longer duration of protection relative to current products, or broader pan coronavirus vaccines, as well as as part included in that is looking at new, more durable monoclonal antibodies, as well as and something that I’ll touch on a little bit more later, advanced development of new technologies that will improve access and enable faster, cheaper, rapid and flexible production of vaccines and therapeutics.
And this could well include technologies that could fill gaps we are identifying in this workshop.
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ROBERT JOHNSON, BARDA [00:12:07]
Our shared task today, again, is not to focus on a particular vaccine and a particular approach. It’s really to understand that technical and other barriers to rapidly switching between strains, focusing on recombinant proteins as an initial point of interest.
We need to understand the critical path and those activities that are the lowest hanging fruit in terms of being implementable without impacting product quality.
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FILIP DUBOVSKY, NOVAVAX [00:28:17]
So these observations have relevance for rapidly bringing recombinant protein vaccines to deployment.
The monovalent approach provides enhanced responses to the selected strain, as well as increased breadth to forward drift variants. At the same time, a monovalent approach reduces the timelines and complexity of developing variant specific assays for testing and release of the vaccine.
As you saw from the primate data, like strains induce comparable immune responses, and the clinical data suggests in the heterologous boost scenario, like strains have comparable clinical relevance responses.
This supports the like strain approach used in influenza that allows manufacturers to deploy vaccines that are not exact matches to the main strain, as long as there’s evidence to justify antigenic comparability. And this will allow manufacturers to manufacture at-risk with the increased chance of manufacturing in acceptable strain.
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RICK CROWLEY, NOVAVAX [00:34:58]
So this is how we’re looking at for late emerging variants. So our, for the 2023 fall launch, we are looking at, BA.5, XBB.1.5, XBB.1.16, and as we get later into the selection process, the amount of data that we can generate real time becomes more and more limited.
So there’s a certain amount of work we need to do up front. But the ultimate things that we have to look at in terms of stability and the process associated with that drug product stability under GMP environment comes very late into this program.
So our assumptions have been and we continue to validate this with our small scale studies, is that in our matrix formulation we see very little difference stability wise of our products. And so we leverage our original studies, our original process studies, to give us confidence that our variants are behaving and meeting the same specs as we move forward.
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RICK CROWLEY, NOVAVAX [00:36:59]
We also feel that a monovalent vaccine performs more robustly, but the bivalents do have their place right now. We don’t see it for the fall campaign.
And so, for us to be able to really meet the needs of the population, we really need to have strong recommendations and direction as close to the end of Q1 as possible because of the timeline it takes us to develop the strain and scale up. We feel that, if we can go to an antigenically-like strain approach, that this timeline then becomes very, very straightforward for us to be able to meet and, and be able to have our product available in the fall.
And so, we’re in discussions with the agencies taking a look at how the label can be generated such that we’re not as specific as to this exact strain for the fall, but that we are in the right class of strains. And so, the XBB-based variant vaccine would be very important for us to be able, given our cross-reactivity, to be able to launch fully in the fall.
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FILIP DUBOVSKY, NOVAVAX [00:39:03]
So we’re prepared to bring either to the market as whatever the composition is set, we’re going to aim at delivering that.
Monovalent is faster and it’s easier. And from our immunogenicity data we think is a preferable one.
If you’re looking toward forward drift and if you’re able to name the composition, which is likely to be the one that goes forward, we don’t see a place for any strains that have previously circulated, compared to XBB.1.5.
QUESTION [00:39:33]
So assuming there’s no new variant that emerges from this point forward?
FILIP DUBOVSKY, NOVAVAX [00:39:39]
Well, I think I agree with what’s been said earlier. We fully anticipate additional variants to come forward. We just need to get to the right branch of the antigenic tree to be able to induce broad responses.
Anything from prototype through BA.5, I don’t think it’s relevant anymore, for XBB ones going forward. So it’s our opinion that if you land this into the XBB tree with a composition, and monovalent has benefits for generating cross broadly cross neutralizing responses to the future drifts.
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FILIP DUBOVSKY, NOVAVAX [00:40:33]
I think the main reason not to include the original one is it’s gone, right? It’s not circulating anymore.
By including it, you do a couple things. You dilute the amount of antigen you have to the currently circulating strain and we think that’s deleterious. You’re also generating immune responses against prototype, which just isn’t around anymore, so that would be irrelevant immune responses.
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JERRY WEIR, FDA [00:37:04]
One of which is the concept of, I think it was mentioned, how do you balance between accuracy and expediency?
And I think Novavax made a good case about how does one define a like strain. And we kind of do this with flu.
I think that is an issue that is is probably broader than for protein subunit vaccines, is how one does define what a broadly like vaccine would be. And so, I think, again, that that’s something that does need to be addressed.
The SUPERNOVA Phase I/III trial is on track. We have fully enrolled the safety cohort and are actively recruiting for Phase III, with sites in over 20 countries. We anticipate results in Q32023 and are aiming to make AZD3152 available as a new option for COVID-19 in the second half of this year.
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I can confirm that we aim to make AZD3152 available as a new option for COVID in the second half of this year, subject to trial readouts and regulatory reviews under EUA.
PASCAL SORIOT, ASTRAZENECA [00:07:09]
Supernova is a trial of our novel antibody AZD3152 for the prophylactic treatment of COVID 19 with potential approval in the second half of this year. Here our aim is to protect people who don’t mount an effective immune response to vaccination, which represents about 2% of the population.
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MENE PANGALOS, ASTRAZENECA [00:30:56]
We also provided new data on AZD3152, our COVID 19 long acting antibody. In vitro studies demonstrated that AZD3152 neutralizes all COVID 19 variants, including Arcturus, the latest variant of concern. And we hope to make AZD3152 available as a new prophylactic treatment in the second half of this year.
ROBERT CALIFF, FDA [00:19:45]
Contrary to what many people seem to believe, the FDA does not unilaterally dictate these sorts of policies. They go through periods of interagency review and public comment, and they often include detailed economic analyses. The trade offs are adjudicated by the little known Office of Information and Regulatory Affairs, or OIRA.
And by the way, I’ve had sort of a hobby in the last month of asking prominent people if they know what OIRA is, and very few people actually do. But this is a part of the Office of Management and Budget, and it’s independent of the FDA.
To the extent these policies influence the underlying substrate of your work, I urge you to watch which policy documents leave the FDA and go into the OIRA process and win. Because this is a matter of public record.
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ROBERT CALIFF, FDA [00:32:48]
What I’d say is that the path of sodium reduction, which I was very involved in 2016, there is a similarity in that there are powerful forces opposed to the efforts in sugar reduction. I tried to describe to you that while we do have authorities, we also, when we go to make rules or guidances that affect the economy, it gets into the mix of multiple agencies having a say in what finally comes out of the hopper.
So we definitely share the goal of reducing sugar. This doesn’t have to be drastic, which is something that was evident in the sodium issue. There are many who advocated a big reduction in sodium right off the bat. That obviously was not going to fly with the balance that exists in the Congress. But we already have evidence of progress is being made, and we’ll continue to make progress as the evidence gets stronger.
And I would hope we do the same with regard to sugar. So I do see some similarities there.
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ROBERT CALIFF, FDA [00:35:23]
I don’t pretend to be a careful shopper. I’ll admit that my wife is a much more careful shopper than I am. It’s unlikely I’m going to turn the package around and read what’s on the back before I buy it. But if it’s sitting there on the front of the package, I think it’s highly likely that people like me, and I think I’m pretty representative, I’m thinking about a lot of other other things when I’m grocery shopping, are going to pay more attention and notice it.
And, you know, one thing that’s in also in the healthy labeling that I discussed is, I don’t need to tell you all, you’re all are experts in this, and I’m not. But it’s obvious that, sort of like all health behaviors, this is a matter of many, many decisions made multiple times per day.
So the pattern of what you buy and the decisions that you make is really more important than any particular moment in time. And the goal is to influence that. So I’ve gotten a lot of confidence that we’re going to figure out how to make this happen. But you shouldn’t underestimate the challenge or the value of your being vocal about it, particularly as it gets into interagency review.
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QUESTION [00:37:35]
I’m wondering if you could talk a little bit about what the agency is doing to ensure the safety of no and low calorie sweeteners?
ROBERT CALIFF, FDA [00:37:45]
Well, you know that there’s a petition in play on this. And so I have to– I can’t go into too much detail, but we’re very aware of the concerns, keeping up with what other countries are doing, and we have a group of people looking carefully at the evidence. So I just say stay tuned on that.
And I do want to– I have to go back to my roots here and say, decisions can be made, but I think this is an area where we still need better evidence. Now doesn’t mean decisions can’t be made in the absence of the very best evidence. But this is an area where I think there’s a lot more that could be learned, particularly now that we’ll have much better access to large population data, through digital records and information about what people are ingesting.
So I’ll say it’s very much top of mind as we look at the overall nutrition issue. This is a hoped-for substitute, but questions have been raised, and we’re looking at them.
QUESTION: Does Virginia conduct any wastewater surveillance of its own for mpox?
ANSWER: The Virginia Department of Health Wastewater Surveillance program introduced short term MPOX testing (6 months) beginning March 13, 2023, at 36 Sentinel Monitoring sites across the state. No MPOX detections have been reported at these sites to date.
The CDC implements a separate contract with an independent laboratory that samples additional wastewater treatment plant sites across the nation. There were originally 15 sites under this contract from Virginia. VDH has transitioned some of these contract sites to the VDH wastewater surveillance program so the current number of sites under this separate contract is now eight. MPOX was detected in wastewater at some of these sites by the contract laboratory.
QUESTION: Across “Dinwiddie, Colonial Heights City, Chesterfield, Prince George, Petersburg City” when was the last mpox case reported?
ANSWER: The most recently reported case of mpox in Virginia occurred the week of February 5-11, 2023. The most recently reported case of mpox in the Central Region of Virginia occurred in November 2022.
We are still learning about the significance of mpox detections in wastewater. Possible explanations for an mpox wastewater detection when no recent cases of mpox have been reported could indicate a case(s) in the community that:
Was previously reported and has an ongoing or unresolved mpox infection
Has not been tested or diagnosed by a provider (most likely due to mild illness), or
Was diagnosed outside of the jurisdiction or state and not reported to VDH.
TEDROS ADHANOM GHEBREYESUS, WHO [00:09:18]
The virus is still changing and is still capable of causing new waves of disease and death. We remain hopeful that sometime this year we will be able to declare an end to COVID 19 as a public health emergency of international concern. But this virus is here to stay and all countries will need to learn to manage it alongside other infectious diseases. The new SBRP will support countries to make the transition.
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MIKE RYAN, WHO [00:16:38]
We don’t have complete information at this this point around the incident. We know that the lab was occupied. It’s a national public health lab. And it it was doing routine diagnostics and reference work for the public health and clinical services in Sudan. And as such, it was dealing with what we consider normal pathogens for the country. And I’ll let Olivier and Abdi detail detail that.
Certainly, this does represent an attack on health care. The occupation of a laboratory denies that service to the hospitals, to the doctors, to the patients. And at this time, our primary concern is the health and welfare of the people of Sudan.
And right now, the major danger to the health and welfare of the people of Sudan is lack of access to clean water, lack of access to food, the risk of direct injury with guns and tanks, and other weapons being used indiscriminately in civilian zones. So when we look at what are the major risks to the civilian population of Sudan, they are the risks.
Having said that, having untrained personnel in a laboratory facility is is not a good thing. That’s why we train laboratories, workers. That’s why we have different levels of BSL, biologic secure– we have different levels of security of biologic agents and we want to make sure that we have strong levels of biosafety in all labs, no matter where they are.
When lab workers are forced to leave a laboratory and untrained people enter that laboratory, there are always risks, but the risks are primarily to those individuals first and foremost to accidentally expose themselves to the pathogen. But there are always obviously secondary risks that someone might leave that laboratory and infect someone else.
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OLIVIER LE POLAIN DE WAROUX, WHO [00:21:22]
We’re working with our colleagues in country to understand the situation a bit better. There’s a risk assessment that is currently ongoing to assess the potential public health risk of this event, which, as Dr. Ryan highlighted, is an attack on healthcare.
The main risk with the lab at the moment is for a national reference lab not to be able to perform its normal public health duties, which puts at risk the population of Sudan at risk, of course, by not being able to detect epidemics if they come up.
We are aware of some samples of pathogens that are being stored in the lab: measles, COVID or SARS-CoV-2, TB, and particularly MDR-TB, cholera, and vaccine derived polio virus. But the assessment is ongoing to better understand what the public health risk might be with those.
And of course, the risk as well of having untrained personnel or untrained individuals in the lab mishandling some of these samples, potentially leading to themselves exposing themselves to those infections is also a risk.
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MARIA VAN KERKHOVE, WHO [00:23:53]
We do see immune escape, which means people can be reinfected again despite being previously infected or vaccinated. But we have not seen a change in severity with the XBB dot sub lineages.
XBB.1.9 currently is around of the sequences that have been shared with GISAID and that we are able to analyze at a global level is around 10% of the sequences. And putting that into context, XBB overall is dominant worldwide.
So this just indicates to us that the virus continues to evolve and it will continue to evolve because the virus is circulating pretty much unchecked. And what we need to be able to do is to keep surveillance up so that we have people that are tested first and foremost to ensure that they get into the clinical care pathway, but also so that we can monitor the virus itself, understand what each of these mutations means, so that our technical advisory group for virus evolution can carry out these risk assessments and so that our technical advisory group for COVID 19 vaccine composition, this is the TAG CO VAC, can make an updated and informed decisions about vaccine composition.
And in fact, they will be meeting very soon to discuss that because we have to remain vigilant.
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KATE O’BRIEN, WHO [00:26:39]
So the measles outbreaks are happening because of these, what we call immune gaps, large sections or substantial sections of the population that aren’t immune to measles.
The backsliding in the immunization program as a result of the pandemic over these past three years has resulted now in 25 million children in 2021 alone who didn’t get vaccinated with measles vaccine. That’s the first dose of measles and an additional 15 million on top of that in 2021 alone that didn’t get their second dose of measles vaccine.
And so, this is the critical nature of being able to press the accelerator pedal to enhance the immunization program in 2023 to catch up all of those people who didn’t receive measles vaccine to restore the immunization programs and to strengthen them even further so we don’t have further left outs moving forward.
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ABDI MAHAMUD, WHO [00:29:52]
On the situation in Equatorial Guinea, we have seen quite a detailed investigation done by our partners and the ministry of health, just appreciating our U.S. CDC colleagues for the detailed investigation done under the leadership of the government.
As we said previously, the government has been sharing update on Twitter. We had the last case onset reported on 20th April. So I just wanted to clarify here some point that caused some confusion. Maybe senior officials or some even the media. When we talk about countdown, it is the last exposure, potential exposure.
So as we speak right now, we have one patient still admitted, and that– WHO has three criterias, when we start that 42 countdown, is after that when we have two negative tests for that. So as we have seen, in this one, I take this opportunity to Tanzania, which just started the countdown yesterday, on 21st April, after two PCRs.
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ABDI MAHAMUD, WHO [00:31:11]
So in terms of the epi, what we are seeing in the trends are, these are clusters that are interlinked. One of them, we didn’t know where it was. That, and eventually, it’s part of the existing cluster.
So we are seeing interlinked clusters spread across geographically, whether it be Mbini, Mongomo, or Bata, but we haven’t seen a widespread community transmission. Having said that, the risk is still there. Ten weeks on it. This may be the second largest MVD outbreak that we are dealing with, not only for Equatorial Guinea but also to the neighboring country.
So we just would like to take this opportunity to appreciate the leadership of the ministry of health, all the government apparatus, to safely contain this outbreak so that we don’t see a spillover to the neighboring country.
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MIKE RYAN, WHO [00:33:32]
I believe it’s a reasonably straightforward job to shut this down. But I think what WHO would like to see is continued vigilance, continued surveillance, continued open, transparent engagement with communities. And I believe this epidemic will end.
But as we’ve seen in the past, one unusual event, one unfortunate amplification, and we could be in trouble. So I think this is the the concern we have. So we’re not saying by any means that there’s a massive undetected problem out there amongst the population in Equatorial Guinea. I don’t think that’s the case at all.
But while the hemorrhagic fever is spreading or moving in a human population, we need to be extremely cautious and vigilant at all times.
NAMANDJÉ BUMPUS, FDA [00:43:21]
It’s great to be here with you and talk about some of the work we’re trying to do to advance alternative methods. So these essentially are tools. It could be an in vitro method. It could be an in silico approach where we’re trying to essentially reduce, replace, in some instances, refine the use of animals in the preclinical context. So the emergence of new technologies really held a lot of promise for this goal.
So, for instance, things like organ on a chip, I know that many of you probably are doing work on that, and we certainly have work on that at FDA. Other approaches, such as in silico tools, I’ll talk about as well. However, we know that animal work plays a really central role in the process of understanding the toxicology of a medical product, for instance, or even in the context of things like foods and cosmetics, understanding ingredients. Additionally, understanding efficacy in the context of products. So it’s been really central.
We don’t expect that there will be replacement of animal testing, but we think that there are opportunities in specific contexts to potentially use these alternative methods.
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NAMANDJÉ BUMPUS, FDA [00:50:40]
So one program that they have is this AI program for toxicology. And so there are many different components to it that they’ve developed. But I want to tell you about this one generative adversarial network model that they’ve been developing, which is called– they call it Animal GAN, where they’re trying to use existing animal data to develop an AI model that can predict outcomes so that we potentially don’t have to do certain animal studies.
Just to give you an idea of where we’re thinking and where we’re going with things. So as you can imagine, we’ve talked about animal models. There can be difficulties. There are challenges. Finding the right model, there can be expense, etc. And obviously there also are ethical concerns as well.
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NAMANDJÉ BUMPUS, FDA [00:52:52]
We’re not looking at, I don’t think in my lifetime, seeing that there’s no longer necessity for animal research. We certainly need it for many reasons. Even understanding things like how the organs are talking to each other.
But there are, we think, contexts where we can successfully use alternative methods and we’re trying to move that forward.
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PATRIZIA CAVAZZONI, FDA [01:24:59]
During the pandemic, we had a sort of a fully virtual approach. Right now, we are continuing to hold the advisory committees virtually, although we have made some improvements.
So for instance, at least for my center, we were only doing audio only advisory committees during the pandemic. We have now moved to this very platform, Zoom, for webinar, which allows a much more sort of interactive sort of a discussion where you actually see you can see each other, you can see the speakers and etc.
We ultimately, what we would envision, is it’s sort of a fully hybrid scenario where both our staff, as well as the panel members and as well as the public can either be here at White Oak or join remotely. And I have to tell you that we have a– when you talk to panel members, they really like the remote option. Why? Because it doesn’t add one day of travel on either end of the advisory committee.
Not only that, but the virtual option is allowing us a greater sort of a flexibility and greater reach when it comes to potential advisory committee members who may have been daunted by, for instance, having to travel from the west coast and so on. So it’s actually broadening our– the pool of potential members of advisory committees. And that’s extremely important because ultimately the foundation of of of an advisory committee is having the right experts to address the right questions.
EVAN SHULMAN, CMS [00:27:39]
Technically speaking, the interim final rule that required nursing homes to test for COVID-19 does end with the PHE.
However, and Will just as you described, we expect nursing homes, long term care facilities, to follow nationally accepted standards, to have an effective infection prevention and control program. In doing so, we believe that there will still be the expectation for nursing homes to continue to test individuals in accordance with national standards like the CDC, such as individuals with symptoms, or those who are close contacts of those who test positive for COVID 19. So those expectations for testing will likely still exist.
In other words, while the PHE is ending, the need to continue to protect ourselves and our loved ones in COVID 19 is not. It’s just not an emergency. So we can’t forget what we’ve learned throughout the pandemic on on what we can do to mitigate transmission and reduce severity of disease by COVID 19. And this also applies to masking and hand hygiene as well.
So continue to follow the nationally recommended practices for testing and other infection control practices. But technically speaking, yes, it does end. But the expectation to test will continue, most likely, past the end of– past May 11th of this year.
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LAUREN OVIATT, CMS [00:29:42]
I would note that the CMS COVID 19 vaccination requirements for health care workers have not changed. Our rule requires that workers be fully vaccinated using the definition included in the rule, which is having had all doses of a multi dose vaccine, or one dose of a single dose vaccine.
Having completed the primary series, you know, sometime within the past couple of years, still continues to meet this requirement. We note that if someone is currently unvaccinated, they can meet this rule’s requirements by receiving one dose of the new bivalent vaccines.
[00:02:16] There are 17 vaccination sites set up by the Department of Health for children requiring the measles, mumps and rubella vaccine. The sites are scattered around the island with the furthest on the west in Amanave and Aunuu to the east. Sites are set up at the department’s clinics and church halls. According to the department of health, they want to increase the vaccination rate to 95% from 89.2%
[00:02:42] As of 2 PM today, in the latest report from the department of health, the number of suspected cases of measles has increased to 37, with 1 confirmed measles case. This is according to the health clinical director, Dr. Elizabeth Lauvao, during a brief interview with KVZK News.
CDC is aware of the case in American Samoa; however, neither the CDC Measles Cases and Outbreaks webpage nor CDC WONDER will include cases from American Samoa because they do not report data to the National Notifiable Disease Surveillance System.
The last outbreak in American Samoa was in late 2019, with over a dozen cases reported to CDC.
How many cases have been hospitalized?
2 admissions in stable condition and isolated away from general population
Do you think transmission occurred at the schools or day care centers that were closed?
At this time we have been able to link transmission in the school that was closed initially and are still investigating other cases.
When was the earliest date of rash onset?
March 20, 2023 self-reported onset for rash, March 23, 2023 presentation to healthcare facility.
We are unable to provide any additional information regarding the patients due to the ongoing investigation and need to protect privacy rights. These two cases are not related to any outbreak in American Samoa. This index case traveled to a foreign country and acquired the disease while in that country. We are unaware of any outbreaks, but the individual brought back the disease to Hawaii. At this point in time, we are unaware of a connection to an outbreak. Here’s a link to the press release: https://health.hawaii.gov/news/newsroom/department-of-health-announces-second-oahu-measles-case/
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American Samoa reached out to Hawaii to see if our DOH State Laboratory Division can assist with testing their specimens. Samples arrived today. Any results of these samples will need to be requested of American Samoa since it is their results, not Hawaii’s. Hawaii is supporting our fellow neighbor island in this current need. Normally, depending on the test, it should take 1, 2 days at the most. Any information regarding American Samoa would need to come from them.
SCOTT ANESI, AMERICAN SAMOA [00:14:19]
As of 1400 today, we are still reporting one laboratory confirmed case. We have increased our probable case numbers to 31 probable cases identified through symptomatic diagnosis and referred for evaluation and confirmation.
The age range for these cases are from two months old to 13 year old, and we have about an even distribution for sex. So it’s affecting both males and females at the same time. And the age group range there is two months to 13 years old.
As you can see our map here, there are two different types of cases here. You will see the index case here, which is case one, as well as case two and three. We are looking at the difference between inactive and active cases. Yellow shows the index cases as well as those that are inactive. But more concerning here is the active cases.
On March 23rd, this is where the first case presented to the health center, which is index case one. An eight year old female from Kanana Fou school. The cases that are surrounding in this area, this is the Ili Ili range where the cases that were all reported back and had links to this initial case started.
The outbreak then started to spread as we saw cases into Fagaalu as well as Pago Pago range that are all linked to this case. We were then able to activate our active surveillance and investigation teams and have been able to find spread cases from Fagalii to Onenoa. And just of this afternoon, we’re reporting case 31, which is the newest case, is linked to case 15 from Aunuu.
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SCOTT ANESI, AMERICAN SAMOA [00:16:52]
All of these breakdowns will show that we have active community transmission in the territory, which is part of the advice that was given to the governor, because we are showing that there is widespread community transmission in all the villages or all of the districts in Tutuila and as well as cases in Aunuu, the advice was to stem community transmission through the closures of schools in the targeted population.
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SCOTT ANESI, AMERICAN SAMOA [00:19:25]
At this point in the investigation, we’ve been able to backtrack it for two incubation periods. So we’re looking at about a month before the presentation of symptoms.
As such, we are not able to definitively say whether this is– where the link is in terms of travel associations. The investigation is still ongoing. There is a team that’s associated with that.
But the primary concern here from the medical team is to pull out and actively seek cases that are active and symptomatic. The difficulties in backtracking the investigations is now that the information is out there, it’s a lot of recollection of information. So some would say, well, maybe they were sick, maybe they weren’t. But there is a team that’s continuing to do the investigation just to establish where the point of reference is for our initial index case.
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SCOTT ANESI, AMERICAN SAMOA [00:20:24]
As reported this morning, only the western state epidemiologists were reporting to us, we did have our call with CDC this afternoon. No region in the United States is reporting cases. We also had a WHO meeting and no South Pacific countries in our our immediate jurisdiction are reporting cases.
However, they did mention that they are starting to ramp up testing in neighboring countries. And so we should know a lot more as their tests come back. So Samoa, they’re sending their specimens to New Zealand. They’re using case profiles similar to ours, and we’ll know a lot more as they ramp up their testing.
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SCOTT ANESI, AMERICAN SAMOA [00:25:21]
So this is our area of interest, the ones that we’re most worried about in the territory, which is why the ECEs and the daycares were closed down first. As you can see for the daycare and the ECE on your left, this is for all daycares in American Samoa.
So 44% of all daycares have their series complete, for those that are eligible to get the vaccine. 34.4% are on track, have already been seen through the health centers, and are awaiting their second dose. The big issue here is this 16% that have had no shots or no– have not come into the health centers at all. So as you can see, this is a large portion of the daycare population.
ECE as they’re a little bit older, is faring a bit better. So 73.8% of those that are in our ECEs have their series complete and only 1% has no shot. 6% of those have one dose, but are out of the range for the second dose now.
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SCOTT ANESI, AMERICAN SAMOA [00:26:26]
So for the elementary coverage, 96.9%, with only 1.5% with no shot and 2% outside of the coverage for their second shot. High schools, 97.4% with one dose here at 2% and no dose at 1.2%.
As you can imagine now, these students that are in elementary and high school have now had a longer period of time without their second dose, even though they need them. That’s why part of the new regimen is to get them started back into the dosing regimen so we can completely immunize those children.
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SCOTT ANESI, AMERICAN SAMOA [00:27:56]
But the main take home message here is that we want to make sure that we’re vaccinating as many of that list that we have. So we’ve got about 790 in the elementary to high school, and 395 in the lower age range. That’s the denominator. Right now, of those, we’ve been able to vaccinate 159.
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UNCLEAR, LBJ [00:40:16]
We had two admissions to the hospital and they are admitted to the COVID ward that was specifically designed to admit a COVID patient during the COVID. We are reserving that isolated ward for all measles admissions. So we have two admissions, two babies that are admitted there right now.
One is a two month old and one is a five month old baby. One of them presented with cough and stuffy nose and typical signs and and symptoms of of measles. And the other one had some cough and some signs, but it was mainly because it was not tolerating any feeds. She was vomiting and that is the reason why she was admitted.
And both of them, at this time, they are doing very well. One of them was supposed to be discharged home today, but there was some low grade fever and that is why we decided to keep the baby back at the hospital to be observed for the next 24 hours. And both of them are most likely going to be discharged home tomorrow. They’re both doing very well. I personally saw them earlier this morning and they are both doing very well. The parents are both looking forward to take them home.
SCOTT ANESI, AMERICAN SAMOA [00:02:52]
So the current update that we are reporting now is we are still at 1 laboratory confirmed case, 29 probable cases identified through symptomatic diagnosis, and referred for evaluation and confirmation at the nearest health center, or through the clinical team.
The age range for these probable cases is 2 months old to 13 years old, 53% males, and 47% females.
As you can see from our map, the legend yellow represents inactive cases, or those cases that are outside of the symptomatic or infection phase. So these cases have had the infection and are now outside of that phase. Red indicates active cases that are currently have presenting symptoms and are infectious at the moment.
So as you can see, the spread that we are reporting for cases is from Faleniu to Onenoa, on Tutuila, as well as one case from Aunu’u. We are not reporting any cases from Manu’a at this time, but the teams from the department of health are monitoring the situation in Manu’a.
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SCOTT ANESI, AMERICAN SAMOA [00:26:25]
Well, at the moment, we are still in the preliminary investigation phase, but because we’re in the acute phase, meaning there’s active transmission in the community, the most important aspect now is to focus on widespread transmission, identify cases that are in the community, get them to be assessed by our clinical team, and to evaluate testing as well as clinical management.
The investigation would warrant, if we go previous, and continue to the investigation to try and see. But at this point in the outbreak, we’ve already identified that there’s widespread transmission.
And so the main focus of the the investigation is to now identify cases that are out in the community, get them seen by the medical team. Produce our mass vaccination campaigns out, as well as making sure that the target population remains at home and lower the susceptibility.
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MOTUSA TUILEAMA NUA, AMERICAN SAMOA [00:32:08]
So we’re currently in the process. The issue that we’re having with the rapid test is that we’ve reached out to our international partners, we’ve reached out to neighboring countries, and none of the partners have the test in stock. And unfortunately, there’s only– there’s not many manufacturers of this test.
So we were referred by our federal partners as well as our international partners to the company. That company is producing the tests for us, and our logistics is currently working on it.
In the meantime, we’ve worked out a solution for testing in Hawaii, through Hawaii state’s department of health laboratory with the CDC. And we are having another call with them today to see about a rapid turnaround time for that.
So if we can create the mechanism and get the samples gone to Hawaii with a 3 to 4 day turnaround, it would still aid in the in the response until such time that we can build up the capacity locally for testing.
So far we are still doing no testing for polio. I’ve checked on the status of this recently and was told that we don’t anticipate being equipped to do so until much later in the year.
ANDREA STEWART, CDC [00:55:43]
In countries with vaccination campaigns, the average post-peak Rt value ranged from 0.75 to 0.88, with a median of 0.87. In countries without vaccination campaigns, the average post-peak Rt value ranged from 0.76 to 1.1, with a median value of 0.93. The difference between these two groups was statistically significant.
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ANDREA STEWART, CDC [00:56:44]
There could be multiple explanations for these findings. First, it is possible that the mpox vaccination campaigns were enough to cause observable differences in transmission at the population level between countries.
However, an alternate explanation could be that countries with vaccination also mounted more aggressive responses overall, with strong campaigns to change behavior and raise awareness about how mpox was being transmitted. Countries that experienced more aggressive outbreaks early may have been more likely to implement vaccine campaigns early as well. Their outbreaks could have declined quickly due to population dynamics or random chance, resulting in smaller post peak susceptible populations.
Because this was an ecological analysis, causality about the effect of vaccination campaigns on country level mpox transmission can’t be inferred from the modest difference in post peak transmission that was observed.
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ANDREA STEWART, CDC [01:00:50]
So all of the countries in this analysis were either high income or upper middle income countries. And as you can see, some of the countries in the “no or unknown” vaccine group were in that upper middle income group. And then some of those countries. And then three out of the two countries implementing vaccines later were also in that group. So there could be a question of vaccine equity in this. But unfortunately, this was kind of all the data I had to show that.
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QUESTION [01:02:13]
You talked about how rapid spread early on could be, perhaps a confounder of sorts, for the results that you did observe. So I guess kind of a couple of ways to look at this. Were you able to look at how Rt early on in the outbreaks, or right before the peak, for that matter, varied by country and later vaccination status or maybe concurrent vaccination status?
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ANDREA STEWART, CDC [01:03:05]
So Rt early on, we definitely could look at that. We didn’t look at that because we were interested in that post peak period because that’s where we were seeing like the biggest differences between the countries. But one of my colleagues is actually conducting a more advanced modeling exercise that does account for the pre-peak Rt values. So you can adjust for that to try to get at that effect.
QUESTION [00:15:37]
Are we prepared for the next pandemic threat?
ASHISH JHA, WHITE HOUSE [00:15:40]
We’re better prepared than we were four years ago.
There is a little bit of revisionism where people are feeling, looking at all the failures and saying, Oh, we’re even worse off. We’re not worse off. We’re clearly better off. Are we as good as we want to be? No, we can be better. But let’s just be very specific in ways that I think we are better off.
If you think about global surveillance now versus what it was four years ago, we’re way better off. We built all the surveillance systems around wastewater, traveler based genomics, the use of genomic based sequencing for surveillance has just dramatically gotten better.
As I mentioned already, I think we’ve made a lot of progress on building vaccines and building vaccine platforms. That’s better. We developed a highly effective antiviral in like 18 months. We’ve never done that against a virus before. I think that is going to leave us in better shape for future viral outbreaks.
So there’s just a series of ways in which we are better. But as I kind of laid out, there’s still challenges. The information architecture meeting needs. I think we’ve got to do a lot more on equity. There’s a whole agenda of work that still needs to be done. But if your question is, are we better prepared? Yes. Are we as prepared as we need to be? Not yet. Not even close. We still have a lot more work to do.
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ASHISH JHA, WHITE HOUSE [00:17:55]
And in terms of my personal future, I have to be honest with you, I just have not made any decisions. As you know, I’m on leave from Brown University, and as of right now, the plan is to go back to Brown, but I have not thought more about this, largely because I’ve been focused on trying to make sure that we get to a better place, that we transition this public health emergency in a way that preserves access to vaccines, treatments, testing, all the other stuff that’s so important. And as that comes to an end, we’ll think more about the future.
ASHISH JHA, WHITE HOUSE
[00:01:25]
So let’s talk about this moment and where we are. Obviously, as a country, we’re just in dramatically better shape. Infections and hospitalizations and deaths are down across the nation, 90, 95%, depending on which metric you use and what time period you compare it to. We are in some of the lowest levels of infection. Infections are down about 90%, even since this winter. And that’s using things like the wastewater data, because obviously cases are harder to monitor now. But the bottom line is we’re in a much better place.
[00:01:59]
Why are we in a better place? I would argue for a few reasons. One is we’ve had an extraordinary vaccine rollout. 90% of adults in America have got at least one shot. We now have availability of therapeutics. But if we really think about how did we get through the last three years and how have we landed so much of a better place, a large part of the thanks goes to all of you in your organizations.
[00:02:25]
Let’s be very clear: hospitals were and have continued to be on the front lines of this pandemic from March 2020 through now. Every time we see a problem or a challenge with a public health system, guess who gets to bear the brunt of it? America’s hospitals. And you have done this in an extraordinary and exemplary way, getting through the last few years. And it’s very clear to me, and I don’t say this just because I’m here, it’s very clear to me that the leadership of America’s hospitals has literally saved tens, if not hundreds of thousands of lives.
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ASHISH JHA, WHITE HOUSE
[00:05:28]
So let me talk about what’s not going to go away on May 12th. So May 12th, we’re all going to wake up. Public health emergency will be over. You can still go into a CVS or a Walgreens and get a free vaccine. If you have COVID on May 12th – I hope none of you do – but if you do, you can go to your CVS or Walgreens or Walmart and pick up your free Paxlovid. None of that changes.
[00:05:54]
In fact, the free vaccines and treatments will continue until the stockpiles that we have in the U.S. government begin to dwindle, until we get to maybe new vaccines in the fall. And over the next few months we’re going to see this transition of the tools of testing, treatment, vaccines that have been so critical, transition to the regular health care system. And by the way, that is how we normalize and manage this virus over the long run.
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ASHISH JHA, WHITE HOUSE
[00:06:24]
Now, obviously, our health care system, for all of its phenomenal strengths, has some challenges. One of those challenges is that there are 30 million Americans who have a hard time accessing it because they don’t have health insurance. So one of the policy decisions we made early is as we made this transition, we have to have a plan for the uninsured. And last week we announced that plan, and I think it’s called the HHS Bridge Access Program, and that plan will ensure that uninsured Americans continue to have access to free vaccines and free treatments for the foreseeable future.
[00:07:01]
I think that’s a really important part of this transition, showing that we can make the transition to the health care system, but not take away access for people. And so you’re going to see more and more efforts like that, to make sure that as we go through this transition, the things that we have relied on, vaccines, treatments, and tests continue to be accessible to the American people. So that is all going to continue.
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ASHISH JHA, WHITE HOUSE
[00:09:37]
But the fundamental idea is, one of the lessons I think, coming out of this pandemic has got to be that when it comes to respiratory pathogens – flu, COVID, RSV, others – we should not require that people have to come into the emergency room or to their doctor’s office. In fact, I don’t want people with respiratory pathogens coming into the emergency room or their doctor’s office, if we can avoid it. Right? (audience applause)
[00:10:03]
Like, who wants that? The idea is people should be able to test at home. We need multiplex testing. So you get one swab, you figure out, is this flu, is this RSV, is this COVID? And then depending on what test results you get, you should be able to call in or Zoom in or whatever the mechanism is and get your prescription for Tamiflu or Paxlovid or whatever the therapy is that your physician decides. But the point here is, is we have got to change the way we do respiratory pathogen management.
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ASHISH JHA, WHITE HOUSE
[00:12:24]
Many of you now live under payment models and payment systems that require you to think about population based payments, population health, and risk based payments. One of the things that you know is that what you do in clinic, what you do in the emergency room, what you do in the hospital wards, is only a part of improving that person’s health. And many of you have gotten a crash course in the idea of social determinants of health and all the factors that influence people’s health outcomes. And increasingly, health systems are being held accountable for those things.
[00:13:02]
This is a place where I think there is a natural partnership with public health. Public health has been working on these things. Public health has a lot of expertise, and I think a closer partnership between public health and health systems can make a big difference in really improving population health.
[00:13:18]
And I think it is that partnership because it cuts the other way as well. Public health agencies have a lot to learn from health care systems. The discipline of delivering health care, the quality metrics, the ways in which health systems are held accountable, public health has not faced that kind of scrutiny. And I think that partnership would make public health better. I think it would make health care better. And I think at the end of the day, it would make health of the American people better.
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ASHISH JHA, WHITE HOUSE
[00:14:18]
Somewhere around 200 to 250 Americans are still dying from COVID related complications every day. It’s not accounting error. It’s not how we’re counting things. It really is true.
[00:14:30]
And when you look at who those people are, there are two things that become really apparent. Almost none of them are up to date on their vaccines. And almost none of them got treated early during their infection. Another way of saying it is almost every one of those deaths is preventable. And it’s preventable, not with some fancy technology that only a few people have access to. It is preventable through vaccines and treatments that are available literally on every street corner across America for free. That is a remarkable fact.
[00:15:09]
And what it shows you is the power of bad information, the power of misinformation. And it’s a reminder that in a pandemic or in any health crisis, and we see this in lots of health crises, so this is not just about COVID. There is an information need that the population has. People are trying to make sense of the moment, trying to make a sense of what’s going on. And there are lots of people out there who are happy to come in and fill that information need, fill the information gap, and often not for the better.
[00:15:45]
And that’s why I believe it is the obligation of all of us, me, certainly, but all of you as health care leaders of America, to flood the zone with good information because the best way to counter bad information is with good information.
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ASHISH JHA, WHITE HOUSE
[00:19:48]
If you’re five or over, you just need to make sure you’ve gotten at least one bivalent vaccine. If you’re 65 and over, or immunocompromised, it is reasonable– and it has been at least four months, it’s reasonable to get another bivalent vaccine. So the second shot of bivalent is really for people who are 65 and over or immunocompromised. And that’s because now we have about three studies that suggest that that can really make an important difference.
[00:20:13]
So for people under 65, just get a bivalent, one bivalent, you got one in the fall, that’s great. You’re done. For people 65 and over, if it’s been at least four months since you’ve gotten it, it’s worth getting.
ROBERT CALIFF, FDA
[00:01:27]
There’s no question our country is divided. And we’ll talk more about that. And I’m sure it’ll come up over and over in the meeting here, I hope it comes up directly because, if we don’t talk about this, we’re headed for even worse trouble.
[00:01:45]
So, I mean, one nice thing about the FDA is that we often are held into a particular box of science and medicine and rational decision making because the history of the FDA and the numerous court cases over the year that have confirmed the role that we play. But there’s no escaping the interaction that we need to have with the political environment as decisions are made and as laws are enacted with rules and guidances, which by their nature are inherently involved, political considerations and back and forth.
[00:02:22]
So I would describe the Obama years for me as genteel and intellectual and a lot of fun. I would describe this year as hand-to-hand combat really every day in dealing with very fundamental issues with things like supply chains and which every commodity we regulate now is experiencing supply chain disruptions except for one, and that’s tobacco, the one that I wish had supply chain disruptions. But somehow they figured out something that the rest of you all haven’t figured out how to get the right supply to the right people for what they want to achieve.
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QUESTION [00:15:13]
And you have, I think I have the quote right, you’ve said that misinformation is one of the leading causes of death in the United States. So talk about what you’re trying to accomplish. I know you have a website now from the FDA where you’re reporting data on misinformation. Well, what do you mean by that? How has the public lost trust? And then I want to get into what universities can do. I know one of your other favorite topics of dealing with misinformation.
ROBERT CALIFF, FDA [00:15:39]
So first of all, I want to modify my statement. And I’ll keep working on this, to try to get it right. I would say I actually believe it is the leading cause of premature death in the United States.
[00:15:49]
And it just– that stems from the old quote that you’ve heard. Life is a sexually transmitted disease with 100% mortality. So we’re all going to die. (audience laughter) And there’s nothing wrong with dying. It’s part of, you know, part of life, really.
[00:16:03]
But dying early because you didn’t do something that people who are knowledgeable know would save your life– that’s really tragic. And if COVID provided the world’s best example. Hundreds of thousands of Americans died who would not have died had they gotten a free vaccine or had they gotten Paxlovid if they got infected and they were high risk.
[00:16:29]
NIH just did an analysis from mostly academic medical centers. You’ve probably seen it. But after the approval, the EUA, for Paxlovid, only 9% of eligible people got it. And when the real world evidence was analyzed by the best methods, there was an 80% reduction in mortality in those who got it compared to those who didn’t. And so you got to say, what– what’s what’s wrong here?
[00:16:56]
And, we’ve talked for years about statins and other areas where people are dying prematurely. If we look at gun violence, there’s another example, leading cause of death now in people under age 35. (crosstalk)
[00:17:16]
And we’ve got– we’ve lost our way in terms of how we communicate with people about it. I think it’s deeply embedded in the disparity issues that we talk about.
At this time, the U.S. government will continue to oversee the distribution of PAXLOVID, and eligible U.S. residents will continue to receive the medicine free of charge (other administrative fees may apply). A transition to distribution and reimbursement through a more traditional U.S. commercial model is dependent on a number of factors, including existing U.S. government supply of PAXLOVID, and we are not able to share specific timing on U.S. commercialization at this time.
Following commercialization, we will also work to help ensure the appropriate patient support programs are in place to facilitate rapid access for eligible patients, as treatment with PAXLOVID must be initiated within five days of symptom onset.
…
Pfizer remains committed to ensuring equitable access in the U.S. and around the world.
We expect that most people in the U.S. will continue to pay nothing out of pocket as the COVID-19 vaccine transitions to the traditional market.
Eligible U.S. residents without insurance will be able to access the COVID-19 vaccine – for free – through our patient assistance program, and we will continue to meet our commitment to donate doses made to lower- and middle-income countries.
Healthcare professionals who wish to vaccinate an uninsured patient with Comirnaty should contact the Pfizer Patient Assistance Program to understand the eligibility requirements.
QUESTION [00:24:24]
You said something about the public health emergency, which is ending on May 11th. What are, from CDC’s perspective, what are some of the implications of that?
ROCHELLE WALENSKY, CDC [00:24:33]
So one of the big things that we’re working on is the data issues, right? So with the public health emergency, and the sort of long runway that it took to get the data use agreements, and sort of some changes that have happened over time in terms of how people are using PCRs versus how they’re using antigen tests, there are some data that we’re not going to get, and there are some data that we will continue to get.
So I do believe that, from a respiratory virus standpoint, we will have a really good window on how COVID is doing because we will have systems in place that are actually better than our current surveillance systems for influenza and RSV, and we do that pretty well every year.
That said, the public has become accustomed to seeing some data from CDC that we will not be able to provide anymore. We will not get case data. The viability of those case data in general, and the– it is limited at this point. The frequency at which we get hospitalization data may be a little bit less.
So those are the kinds of things that we are working on, but again, not necessarily within CDC’s authorities to change.
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ROCHELLE WALENSKY, CDC [00:52:10]
The other thing I think that’s really a challenge is there could be ten places where we might put out a new guidance, or might have a new area, in nine, there’s agreement. The 10th is what makes it to the news, right?
And so all of that areas of dissecting the disagreement, which often happens in an academic setting, or often happens in a society conference, where you have a pro and con on what should we do about X? That’s now in a two minute news spot. So, a public that is really grounded and wanting to know, what should I do? They’re not focusing on the nine of ten things. They’re focusing on that one, which really makes it hard for the public to digest.
We did actually, just last month at CDC, have a seminar on decision science. And part of what that– and that is sort of the field of simulation and cost effectiveness, and how we manage uncertainty.
The second– I’m a decision science person– the second chapter in the book in my most used book is managing uncertainty. What do you do with the fact that we may not have the data points for all of these questions?
And to have the agency recognize that we– there may be things that are not as efficient as they were a while ago. There may be systems that we’re using now, that we have one that we’re using now that may not be as efficient. We got the information that we needed from said system, so it’s time to sunset that. That’s hard.
But I think people are starting to sort of realize that we don’t actually need the data point to the 100th decimal point. What we really need is to say it’s low enough that we should move forward. So that’s a lot of the work of decision science, and we had a really productive scientific seminar on this, with all of our senior leaders, and real enthusiasm on using those kinds of methods to make decisions.
…
QUESTION [00:55:25]
Given the political interference we saw in this country, in the past administration, and in so many other countries, is there a way to protect CDC by giving it larger degrees of freedom, hopefully a Federal Reserve kind of independence?
…
ROCHELLE WALENSKY, CDC [01:00:05]
Yes, I think that we– it would certainly be better to have an independent – well I’m, to have– it would be a different different place to have an independent health agency.
I will say, as I’ve been in this role, one of the things that we also really need to recognize is the whole interagency USG. Health has to have a seat at the table, but it can’t have the only seat at the table. And as we’ve had discussions, and so much of the work that we do at the policy level, has to have the Department of Ed, and has to have Labor, and has to have–
If we are so monocular, as to only look at health, then we’re not looking at the economic impacts which, potentially, downstream could lead to worse health outcomes. So we really do need to be able to see the whole picture.
I don’t think we’re moving in a direction that you’re talking about. The 20 January 2025 CDC director, whoever that may be, will be Senate confirmed. I was not.
So policies are not moving in that direction, unfortunately.
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ROBERT CALIFF, FDA [00:27:28]
Well, as you know, Senator, the matter is currently pending before the Supreme Court. So I have to be brief and concise.
But I will say that we are concerned about the potential future impacts of this case, as reflected in the extensive briefs that have been filed by the Department of Justice on our behalf. This includes a wide range of concerns ranging from the well-being of patients, including women who need access to this drug, the pharmaceutical industry, and our ability to implement our statutory authority.
So the considerations are extensive.
…
SEN JOHN HOEVEN [00:44:37]
So my question to you is, will you commit to following the decision of the courts with respect to the drug and how it’s handled?
ROBERT CALIFF, FDA [00:44:47]
I’ll just say the FDA intends to comply with any court orders.
…
ROBERT CALIFF, FDA [00:53:28]
Well, as we discussed already today, our decisions are based on the latest science, the best data we can find, the weighing of risks and benefits by professionals, who are full time civil servants, without financial conflict.
And there is concern in this case about the impact on a wide variety of things, including patients, women who need access to a drug which is approved, the pharmaceutical industry itself, because of the threat to the separation of this decision about what’s approval and what’s not, sequestered away from political influence.
So these are all concerns that we have.
SEN PATTY MURRAY [00:54:12]
So I take from your answer that this, of course, could have an implication on mifepristone, but also on the process that all of the drugs and tools that are going through the FDA?
ROBERT CALIFF, FDA [00:54:22]
This is well reflected in the extensive briefs that the Justice Department has filed on our behalf and are publicly available.
…
SEN CINDY HYDE SMITH [00:59:10]
But if the Supreme Court allows the lower court rulings to go into effect, will the FDA fully comply with the decision without delay, and not attempt to flout the ruling under the guise of some kind of enforcement discretion? Would you apply it immediately?
ROBERT CALIFF, FDA [00:59:33]
First, let me just– one small thing that you said. Not such a small thing, but I do want to offer a different viewpoint on the adverse event reporting. Adverse event reporting is required of all drugs, including this one. The reporting of adverse events is not being ignored in this case. It’s required. Just like with all drugs.
What was done was to take away a separate form that’s different from all the rest of the drugs.
But with regard to your question, we’re confident the law is on our side. We’ve appealed. The district court’s decision to the Supreme Court and have sought a stay pending that appeal. But FDA, as I’ve said already, does intend to comply with any court orders.
DAWN O’CONNELL, ASPR [01:36:00]
So the 5 billion, I think we’ve been very clear that we’re running out of COVID dollars. We have indicated that over and over again, but we didn’t have the winter surge we expected, and we had additional funds.
Now that we’re winding down the public health emergency, now that we’re moving these products to the commercial market, we looked across the remaining balances, and are working to make sure that we’re spending them as effectively as possible.
And we think creating the next generation of tools to protect Americans from COVID is a reasonable use of these next dollars.
PETER MARKS, FDA [11:18:20]
Now we realize that this updated regimen is still somewhat more complicated than desirable, but we view it as an interim step as we move into the next cycle of strain selection, which is coming up this late spring, early summer, as I noted, further consolidate and simplify the regimen as we further update the labeling for these vaccines.
Ultimately, our goal is to have the regimen simple enough for both patients to easily understand and providers to easily administer.
For now, though, the key message that I’ll leave you with, as I conclude, is that at this time, for older children and adults up to age 65, a single bivalent vaccine is appropriate for prevention of COVID 19, from our perspective, in our current emergency use authorization.
…
PETER MARKS, FDA [11:19:48]
So for those who have received non-mRNA vaccines, the there is essentially we were in a situation where those vaccines, we will be discussing with those vaccine manufacturers how to further update those vaccines so that there will be options available as we move forward.
But they– yesterday’s actions do not affect those other vaccines at this time.
…
GEORGINA PEACOCK, CDC [11:26:56]
So I want to first of all, talk to you about what will change in this– when the public health emergency ends. And then I’ll talk about some of the things that are not going to change.
So first of all, we are expecting a reduced submission of vaccine administration data from some jurisdictions. And so that’s going to limit the completeness of the administration data that we can report on a national level.
We have been working with jurisdictions to sign an extension of their COVID 19 data use agreement that will extend for most states that ability to get data from them until the end of 2023. We do expect that there may be a few jurisdictions that don’t submit that data based on state laws that they have, and other things that are impacted by the end of the public health emergency. But we still will be getting the majority of administration data on COVID 19 vaccine.
…
GEORGINA PEACOCK, CDC [11:40:30]
I think I want to emphasize that there isn’t a complete cessation of reporting of administration data. There will be some decreases after this public health emergency. And most of that is related to state laws that prohibit actually sharing this data with the federal government. We are working with our state partners to see if there are ways to continue to receive both vaccine administration data related to COVID, but also to routine vaccinations.
And I think putting both an extension of the data use agreement into place for COVID, and then also routine vaccination data use agreements, are also being sort of negotiated right now and being put into place.
For COVID vaccine, there still will be– there still is in the provider agreement, so every provider that provides vaccines, and at our peak, we had 120,000 providers that provided COVID vaccine, there is still a provision within that provider agreement that they need to report administration data of COVID vaccine. So it’s possible and it’s probable we won’t have the full picture of what is going on nationally. However, state health departments will still have this data within their immunization information systems.
And so while this is different, I think we still will have different ways to look at ensuring equity as we move forward.
I’m not going to say it’s– I mean, it does add some challenges, but I think we will continue to do the work that we’ve been doing. We’ve supported a lot of partners who have been working with community based organizations to look at both the access issue, and also the confidence issues. And that work is continuing to be funded and continuing to move forward.
…
TOM SHIMABUKURO, CDC [12:13:46]
So this graph shows participation in V Safe over time. The blue bars represent active new active registrants and you see the the scale on the left hand side there. And then the yellow line represents COVID 19 vaccine doses administered in the United States. And you see the scale on the right hand side there. Keep in mind, these are not– these are different scales, but generally you can see that that active registrants paralleled doses administered.
And really most of the use of V Safe, as far as new registrations and surveys, occurred in the first year of the vaccination program. And in fact, most of that, the new registrants, were in the first half of the first year of the vaccination program. And use has actually waned pretty rapidly. And is at a pretty low uptake at this point.
Another thing to notice is that you see active registrants and doses administering kind of paralleling in early on where you see a lot of doses administered and a lot of new registrants. And then as you go on, these peaks in doses administered largely represent new authorizations and recommendations.
And it’s hard to see because of the scale is a little difficult. But we didn’t really see a corresponding big surge in uptake with these new registrations. So probably there are a lot of early adopters, early on in the program, which is not totally unexpected. Next slide.
…
TOM SHIMABUKURO, CDC [12:15:34]
So as far as the next step for V Safe, the timing for the final registration and completing of surveys will be announced soon. Follow up will continue on reports of medically intended health events.
The next generation V Safe is under development. We plan to collect data on new vaccines once it is developed and implemented. The new V Safe will allow greater flexibility for surveys and use IT CIT infrastructure. It will be designed to permit long, longer term support for collecting data rapidly from a large number of vaccine recipients.
…
TOM SHIMABUKURO, CDC [12:21:02]
I don’t think the data are sufficient to conclude that there is a safety problem for ischemic stroke with the Pfizer vaccine in this age group, or that there’s a safety problem with simultaneous administration of COVID vaccines and flu vaccine.
There is additional work that’s going on. FDA has a study that’s in progress. And CDC, along with its VSD partners, will continue to evaluate the data. So I think there will be more to come on this. But we don’t feel that the at this point, the data are sufficient to conclude that there is a safety problem here, let alone make a change in recommendations.
…
SARA OLIVER, CDC [00:28:14]
Overall, FDA removed the authorization for monovalent mRNA products. We’ll note that the BLAs are still in place, but the vaccines are either expired or have very limited doses in circulation.
At this point, the bivalent mRNA COVID vaccines are now authorized for all indications. And note that there were no changes to the current language in the other COVID 19 vaccine authorizations, such as Novavax or the Janssen vaccine.
…
SARA OLIVER, CDC [01:02:05]
So based on these and other data, some population of young children likely still need a prime and a boost to optimize immunity. In addition, young children will continue to age into the vaccine recommendations at six months, and could be SARS-CoV-2 naive.
I’ll note that additional data are forthcoming to evaluate the benefits of a multi-dose primary series in all children ages five and younger, or if those recommendations could be simplified further. We look forward to presenting both a cost effectiveness analysis in children, as well as additional antibody data in children, at future ACIP meetings.
…
SARA OLIVER, CDC [01:03:02]
So the overall implications for this, for CDC recommendation: a COVID vaccine framework for a single dose could be easy for COVID vaccine providers to implement and for the providers and for the public to understand.
The current recommendation for a single dose may evolve over time and could move to an annual recommendation. But with these updates, a single bivalent dose would be recommended for everyone ages six years and over.
And I just want to note that for most people the implication of this update means no change. The doses needed, the action taken after this, are exactly the same. If someone has not received a bivalent vaccine yet, they are recommended to receive one regardless of their previous vaccine history, then children six months through five years would overall receive at least two COVID vaccine doses, and at least one of those would be a bivalent vaccine.
…
SARA OLIVER, CDC [01:09:04]
We discussed the actions taken this week by FDA and soon by CDC. However, this isn’t all something we can achieve in a single action. Next slide. We want to acknowledge that future steps may be possible.
All these updates today were focused on mRNA vaccines, but in the future we may be able to have simplification for all COVID vaccines.
Then, while we look to the possibility of updated vaccines this fall, we’ll continue to evaluate data driven ways to simplify the pediatric program, and will continue to review data for this at upcoming meetings.
And as always, we continue towards a goal of flexibility and simple guidance.
…
EVELYN TWENTYMAN, CDC [01:21:52]
I’d now like to summarize here what it means to be up to date with COVID 19 vaccines in the context of the new recommendations.
Most important is the first bullet here, simple and singular. If you’re age six years or older, and got a bivalent, that is to say updated COVID 19 vaccine, you are up to date.
Children younger than age six need to follow the recommendations customized for them.
People at higher risk of severe COVID 19 disease, because of their age, have the flexibility to receive an additional bivalent mRNA dose, and at higher risk of severe COVID 19 disease, because of moderate or severe immunocompromise, have the same flexibility, and more.
And alternatives remain. If you are unable or unwilling to get a recommended bivalent mRNA vaccine, you will be up to date if you got the Novavax COVID 19 vaccine doses approved for your age group.
…
CAMILLE KOTTON, ACIP [01:35:33]
So could I ask a clarifying question? What about for children six months through four years of age who are immunocompromised, who had Pfizer?
EVELYN TWENTYMAN, CDC
We do not perceive that that is authorized at this time. I don’t know if Dr. Kaslow or others if you want to comment?
PETER MARKS, FDA
Hi, it’s Peter Marks. So the issue here had to do with, we do have to do these things based on data, and we did not have data to support that additional dose there. We obviously will update things as soon as we have data. But for right now, I think we’re sticking with where we have data to support our product information.
CAMILLE KOTTON, ACIP
Thank you, Dr. Marks. So does that mean that for immunocompromised children, six months through four years of age, who had a prior Pfizer, that they can’t get any additional vaccine doses moving forward, until such time as you have the aforementioned data and FDA makes a change?
PETER MARKS, FDA
Correct.
CAMILLE KOTTON, ACIP
Doesn’t that potentially leave that immunocompromised vulnerable population at higher risk? So do you do you have a time frame on when you might be seeing data?
PETER MARKS, FDA
I think we would be– we would be updating this as we move towards our fall campaign of vaccination. In other words, once we have our strain selection. Unfortunately, this was where we were left, with the data that we had at hand.
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SARA OLIVER, CDC [01:55:47]
I do not think that getting a dose now would preclude somebody from getting a dose in the fall. Obviously, we don’t have formal recommendations, so I can’t speak to anything more certain, but we’re not anticipating that that changes now would would somehow make people ineligible in the fall.
Understand that there are people who are reasonably healthy, and maybe older adults, who want to wait until the fall. I think I think that is absolutely an option. But specifically for children, it would be immunocompromised children who would be eligible for this kind of additional dose, and would defer to the health care providers. But I think they should be able to get a dose now and potentially get one in the fall as well.
…
SARA OLIVER, CDC [02:17:40]
I will say we have an upcoming work group call focused specifically on this and hope to to bring this to an upcoming ACIP meeting. That was true when I said it in February. And apologies that this was an emergency meeting that was added, but that is still on the plan to review additional data and continue additional discussions.
At this time, additional doses specifically related to pregnancy aren’t authorized, but we look forward to continuing to review data and discussing.
…
MARY BETH HANCE, CMS [02:22:30]
I would just say that we are, CMS is looking into this, with these changes in recommendations, and will be working with CDC. But as of right now we don’t have any updates. We’re looking into it.
…
JESSE HACKELL, AAP [02:34:12]
Dr. Peacock mentioned the commercialization, which is being looked at for the next several months, and the AAP is quite concerned about the impact of commercialization on access to the vaccines.
Given that up until now, any VFC provider has been able to access the vaccines at no cost, and yet we still have really dismal rates of completion of the vaccines in our youngest children, our fear is that when the vaccines are commercialized, VFC will continue to supply the vaccine for the over 50% of all children who get their vaccines through that program. But for the almost half of children who rely on commercially available purchased vaccines, we see a tremendous problem in the making for pediatric providers.
We’ve heard about an estimated cost of the vaccine of between $100 and $130 per dose. We’ve heard about a minimum order of 100 doses at a time. And I think recognizing that many pediatric practices operate on razor thin margins, our fear is that few practices are going to be able to invest 10 to 13,000 dollars up front in purchasing the vaccines, especially because we have no indication how we will be paid for the vaccine or for the administration.
If we lose those providers of the COVID vaccine, our impact on the vaccine rates will only get worse. Our access to the vaccine for our pediatric population will only get worse, if there are fewer providers willing to undertake provision of the vaccine.
So I guess my comment is on the on behalf of the AAP is to urge that when commercialization is considered, particular attention be paid to the providers who undertake the purchase of the vaccines and administration of the vaccines to assure that to encourage them, to incentivize them, to continue to provide the vaccine by assuring that they will be paid adequately for the vaccine and for its administration, both in terms of costs as well as a margin above costs.
And to be sure that any vaccines that are not administered because of low confidence and low parental uptake, that any vaccines which are not administered will be able to be returnable for credit. Otherwise, the fear of a financial hit is liable to dissuade many practitioners from providing and continuing to provide the COVID vaccine. And again, the impact on access will be dramatic.
…
RABURN MALLORY, NOVAVAX [02:43:13]
So we are, at Novavax, broadening our label. Right now we’re submitting data to the FDA around adolescent boosting, so that we can have an indication there. We are also will be moving forward to submit data for subsequent boosts in adults, beyond the first boost.
We do have an ongoing study in younger children to expand into those age groups and we hope to be moving into the very youngest age group, six months to two year olds, in around the May time frame. So we do recognize that there’s a benefit to a broader indication, and we are certainly working hard to gather data to expand our label to that end.
TEDROS ADHANOM GHEBREYESUS, WHO [00:05:09]
Now to Marburg. Marburg Virus Disease in Equatorial Guinea, where in the last week two health care workers that had contracted the virus were discharged from a WHO supported treatment center. There has now been a total of 16 laboratory confirmed Marburg cases. Among these cases, 11 people have died. 23 probable cases of MVD have also been reported, since the outbreak was declared on 13 February.
The most affected district is Bata, in Litoral province, where nine cases have been reported. Today, a new case was reported in a health worker from Bata was being monitored due to exposure from a previous case. The case was detected on the day of disease onset and was given antiviral therapy by a government protocol which is being supported by WHO. WHO calls on all partners to remain vigilant, as there may be undetected chains of transmission in the country.
With partners, WHO is supporting the ministory of health to strengthen surveillance in affected areas and increase laboratory capacity. We are also working together to improve case management, infection prevention and control, protect health and care workers, conduct safe and dignified burials, as well as engaging with the community around risk and staying safe.
WHO is working with neighboring countries to help prepare for any importation. This is a critical moment in the outbreak response in Equatorial Guinea and will take on all of government and all of society effort to stop this outbreak.
…
ABDI MAHAMUD, WHO [00:17:56]
Yesterday, GE confirmed the new case of Marburg. This was a high risk health contact that the patient was being followed up, had symptoms onset yesterday, and was immediately isolated. They reported a minimal level of symptoms and that rapid identification and isolation really helped. And we believe that the contact may not be as large as that. So there’s quite an improvement in terms of the contact identification.
But what we are worried about, the health care infection, nosocomial infection, particularly in this case and the previous one in that. So it’s an area that we’ve been working very closely improving that training. Basically the triage part of it, the screening, triage, and the isolation of a big pillar of that.
We have our IPC pillar lead in country improving that key gap that we have noticed.
In terms of the clinical management, we had a different approach right now where we work very closely with our international pillars and GOARN partners. Both ALIMA and the other organizations you mentioned are part of WHO and with WHO under the leadership of government, we established several isolation treatment centers, both in Bata and Ebebiyin. So we don’t have, like other countries as are in Uganda or in other areas, we don’t do separate. So it’s under the government leadership, WHO has been supporting and establishing that.
So in terms of every country is unique, and the government propensity of accepting NGOs will be different. There were multiple offers coming from those NGOs, been in agreement since they are part of GOARN. We agreed to work together under WHO umbrella to support the ministry of health.
But the last case is just to reiterate again that we are in the midst of the outbreak, viral hemorrhagic fever, whether Ebola or Marburg, are serious and it needs really requires that. So the idea of countdown is not the time for countdown, it is the time to strengthen all the pillars of the response from the community engagement to the IPC to clinical management to the alert, all aspect of the response
…
MIKE RYAN, WHO [00:24:37]
And to that point, you’ll note that we’ve added XBB.1.16 to the list of variants under investigation, or variants of interest, and that’s the second one that’s been added there. That was added yesterday on the 17th of April, and it’s a descendant lineage of XBB. It’s a recombinant of two BA.2 descendant lineages. It was first reported in January 2023. We’ve had 3,000 sequences as of April 17th, and that now represents 4.2% of all submitted sequences.
What’s significant is, a month ago, that was less than 0.5%. So what we’re really seeing is a kind of an estimated growth advantage, some evidence of immune escape characteristics, and therefore this variant may may spread more globally and it may cause a rise in incidence. It may not, but it may cause a rise in incidence of cases. But there’s no sign at the moment, and there’s no early signal, of any increase in severity.
…
MIKE RYAN, WHO [00:28:20]
To my knowledge, we’re not seeing a different spectrum of symptoms or severity associated with this variant of interest, but we’ll certainly review that and get back to you. But I’m not aware of any major shift in symptomatology for this variant, but we are seeing characteristics associated with increased transmission capacity.
…
ABDI MAHAMUD, WHO [00:28:50]
Maybe the journalist was referring some of the media reports of conjunctivitis. These are known symptoms that already is part of COVID. And as Mike said, we are working very closely with the other clinicians.
…
ABDI MAHAMUD, WHO [00:29:02]
In terms of the, as WHO, we believe it is government national leadership and global solidarity. As we said several times, the Equatorial government has learned a lot of lessons from both COVID and established good, robust, not as excellent robust, but a response, is really the time to come in solidarity and support across the world.
Support is not a time for travel restriction. It does not help the world. It’s just harms those countries who are doing the right thing, struggling, these macroeconomic challenges the whole world is facing.
So we had some of them, and WHO is very clear. We issued the DON and we said it’s not the time for travel or trade restrictions on Equatorial Guinea.
A few countries have started screening, which is some rational, and we received the update on that. But it’s not a time for travel restrictions.
ALECIA NAUGLE, USDA
[00:52:33]
I’ll add that we also really are working at the at the farm level to help do biosecurity assessments, so producers can go through their facilities and identify if there’s opportunity for wild birds to get in there, and potentially infect their flocks. I think that’s a really important next step for us.
[00:52:56]
I think you’re leading toward the vaccination question. And so to that regard, we are currently, behind the scenes, having conversations with international trading partners. Dr. Sifford goes to the World Organization for Animal Health in May, and HPAI will be a major topic at that meeting, and she’ll discuss with her counterparts across the world how we need, if we need, to look at vaccination differently.
[00:53:23]
Right now, our partners at Agricultural Research Service are investigating different strains of potential vaccine for possible licensure. And internally, we are determining plans for how we might implement a vaccine strategy.
[00:53:41]
However, right now, today, we believe strongly that our response has been effective. Whenever we’ve identified HPAI in a case in domestic poultry, we’ve effectively stamped it out, and due to the great trade consequences of vaccine, at this point, we’re planning for the future but continuing on the current path.
Novavax on FDA Announcement to Simplify Use of COVID-19 Vaccines – for attribution to Novavax
Today’s U.S. Food and Drug Administration (FDA) announcement that simplifies COVID vaccine booster guidance and vaccination schedules does not impact availability of Novavax’s protein-based COVID-19 vaccine. The Novavax COVID-19 vaccine is still available as an option for unvaccinated adolescents and adults aged 12 and above as a primary series, and as a third dose for vaccinated adults aged 18 and older.
Novavax continues to collaborate with the FDA to develop an updated vaccine for the Fall campaign and is currently manufacturing several vaccine options at risk in preparation for this.
Novavax’s protein-based COVID-19 vaccine provides an important vaccine option for people in the U.S. to protect themselves and their families. Novavax recently announced an extended partnership with the U.S. government, ensuring continued vaccine supply. Access to a diversified vaccine portfolio is vital for protecting public health and future proofing against variants as part of the global long-term strategy to address COVID-19.
PETER MARKS, FDA
[00:08:49]
So those BLAs will stay in place. This happens not infrequently in other situations, with influenza, when there’s a period where there is not a vaccine that’s actively being administered, even though the BLAs are open.
[00:09:09]
What what we need, in fact, in many ways, we’d like to have them remain in place, because they will be the subject, likely, of manufacturer supplements in the future, where they will then update the vaccine composition.
[00:09:27]
And actually I think we see a reasonably straightforward way that that will happen, moving forward, as the vaccines essentially move into the next strain selection after June.
…
PETER MARKS, FDA
[00:12:09]
So right now, the bivalent vaccines appear to help prevent the current XBB.1.5 variants that are circulating from causing severe disease. I think that’s important. And what will happen is, as we come into June, we will be looking at all of the different circulating variants.
[00:12:38]
As you may be aware, there are two new variants that are being watched closely. One, Hyperion, and the other, Arcturus, otherwise known by XBB.1.9.1 and XBB.1.16 and we’ll be looking closely at those to see what’s going on.
[00:13:01]
It turns out that right now, since those– the same spike protein is present on XBB.1.5 and those other variants, to a large extent, we think that it may be, may turn out, that as we go to select, we’ll be able to find something that is able to cover them all. But that will be the topic of the discussion in June.
[00:13:26]
I think this is going to look, as you’ve implied, very much start to look very much like what we do for influenza. And I’ll acknowledge that it’s true, COVID 19 is not influenza. The SARS CoV 2 is not the influenza virus. But that said, we’re using that public health model, where we’ll look to do our best to select what we believe to be likely to circulate the following fall winter season, and use that in the vaccine composition.
[00:14:07]
So to try to protect as many people during the season in which respiratory viruses tend to wreak their havoc, which is fall to winter months of the year.
…
PETER MARKS, FDA
[00:20:25]
And it took us a little longer to get to where we were now, because this was a very major action of consolidation here, where we move to a single vaccine composition for everyone. We also wanted to make sure that we felt very comfortable with the data supporting the second dose of the bivalent boosters for those who we have authorized it.
[00:20:54]
And I think that time gave us a good chance to look at data, some of which has only very recently come out in public, to be able to feel comfortable that that this is a reasonable thing to do.
[00:21:12]
So, again, large action, but hopefully setting us up for success, because if anything comes out of this action, we’re hoping that it can encourage people who have not received the bivalent booster to go out and consider getting one, because even in the most significant target population of individuals 65 and older, CDC recently reported that only 42% of eligible people have gotten a bivalent booster.
[00:21:43]
So we’d like them to know that it’s a good idea to do that now and and hopefully set us up for success as we move into fall and winter for people to have a better understanding of the potential benefit that these vaccines can bring.
…
PETER MARKS, FDA
[00:29:13]
So let me just kind of walk that back just a bit to say that, you know, as we come into this advisory committee meeting in June, we’ll discuss kind of the cadence of future vaccinations. So that’ll be a discussion of using our existing vaccines, or updated vaccines based on strain composition, what the recommendation should be.
[00:29:37]
So they– I should be clear that the recommendation currently, we don’t have a– it’s not like we have an annual recommendation yet. The, right now, we have recommendation for a single vaccine with the bivalent. But that will be discussed, that recommendation of what to do for future years, will be discussed at the advisory committee.
[00:30:03]
Is it possible that this will be something that will happen on a regular basis? It is, but that’s something for discussion at the advisory committee.
JOANNA PRASHER, CDC
[00:09:54]
CDC staff have been deployed to Equatorial Guinea and continue to support the ministry of health in providing risk assessments for identified contacts in health facilities, including those near the large city of Bata.
…
JOANNA PRASHER, CDC
[00:10:40]
Currently, there’s no evidence to suggest that these two outbreaks are related. Most experts agree that these likely represent two independent animal to human spillover events, but we are still working with our colleagues in the governments of both Tanzania and Equatorial Guinea to obtain the sequencing information that would help us to further clarify that.
[00:10:59]
To date, there has been no confirmed cases of Marburg virus disease related to these outbreaks either in the United States, or in any other countries, outside Equatorial Guinea and Tanzania. Therefore, the risk to the United States, we feel, from these outbreaks is low.
[00:11:15]
But CDC is working diligently with our interagency, international, and multilateral partners to support the governments of both Equatorial Guinea and Tanzania in containing these outbreaks as soon as possible, and as mentioned, ensuring readiness just in case.
…
JOANNA PRASHER, CDC
[00:11:47]
Given the low risk of an imported case of Marburg to the United States at this time, we are not recommending post-arrival risk assessment or monitoring of these travelers, but we are providing recommendations to these travelers about what to do and signs and symptoms to self-monitor for, after they return to the U.S. and to do this, as of March 25th, we began text messaging travelers arriving in the U.S. from both countries Equatorial Guinea and Tanzania, and asking him to self-monitor for 21 days after they returned from either impacted country.
[00:12:17]
We are also displaying educational messages about Marburg on airport monitors located at ten international airports in the United States, which received the majority of travelers from these two countries. And again, these messages advise travelers that, if they were recently in Equatorial Guinea or Tanzania, to watch themselves for Marburg symptoms for 21 days, and what to do should they get sick.
…
JOANNA PRASHER, CDC
[00:12:39]
On March 31st, we also updated our interim guidance on risk assessment and management of persons with potential Ebola virus or Marburg virus exposure. And these revised recommendations really are aimed to reduce the burden to our state, tribal, local and territorial health departments.
[00:12:55]
And as part of this, in support with our STLT partners, as of April 4th, we are providing them the contact information for the passengers in their jurisdictions arriving from Equatorial Guinea or Tanzania. Although again, it’s important to note that we are not currently recommending that they conduct risk assessments for, or monitor, these travelers at this time, but we are providing them this information for their situational awareness.
…
JOANNA PRASHER, CDC
[00:13:55]
33 of our laboratory response network labs are able to now test for both Marburg and Ebola viruses under CLIA, using the BioFire Warrior Panel, and six additional LRNs are currently working to get Marburg verification under CLIA up and running.
[00:14:11]
Eight of these regional emerging special pathogen treatment centers can also test for both Marburg and Ebola under CLIA, again using the BioFire Warrior Panel, and the two remaining RESPTCs are also working on this.
[00:14:22]
Testing for Marburg virus under CLIA is also now available at CDC, using both the BioFire Warrior panel and a high throughput assay. And we’re also developing an additional high throughput assay that could be submitted to FDA as a pre-EUA, should further laboratory capacity be needed.
[00:14:39]
NIH is also completing BioFire Warrior Panel verification for both Ebola and Marburg viruses.
…
JOANNA PRASHER, CDC
[00:14:45]
On the treatment side, all ten of the RESPTCs, as mentioned, can accept both adult and pediatric patients if needed. And the NETEC, which is the group that provides education and training for the RESPTCs, is specifically working to expand its in-house pediatric expertise and educational materials and will be developing a global grand rounds in the future focused on pediatric challenges.
…
JOANNA PRASHER, CDC
[00:15:38]
So probably some of the most important efforts that are in place right now: the government of Tanzania has been actively screening travelers and exiting Tanzania as well as entering Tanzania, for some time. And we’re working to support them in any efforts they need to do temperature checks, etc, for people that are transiting out of that country.
[00:15:59]
And we’re also working with the ministry of health in Equatorial Guinea. We’ve provided them some remote support around some of their border health measures that they’re taking internally as well.
[00:16:08]
CDC, also as is our custom, has been reaching out to any non-governmental organizations that are working in either of those two countries that are U.S. based and might have employees or others coming back to the United States, and just working to make sure that those travelers are very aware of the situation on the ground in both countries and the measures they should be taking to protect themselves and others as they return.
On the record from Vivien Dugan (PhD), acting director of the Influenza Division in CDC’s National Center for Immunization and Respiratory Diseases (NCIRD):
“CDC believes the risk to the public’s health from H5N1 bird flu continues to be low, despite some changes seen in the genetic sequence of viral RNA from the H5N1 patient in Chile. Those genetic changes have been seen previously with past H5N1 infections, and have not resulted in spread between people.”
“Nevertheless, it’s important to continue to look carefully at every instance of human infection, as well as other mammalian spillover events, and to track viral evolution in birds. We need to remain vigilant for changes that would make these viruses more dangerous to people.”
Here is a nice summary of the categories of changes these H5 viruses are likely going to need to make to switch to the human host. https://www.science.org/content/article/bad-worse-avian-flu-must-change-trigger-human-pandemic
But I lump the groups of changes necessary into three pots (the science article lists 4). These are
Changes to the receptor binding site in the hemagglutinin (HA) protein.
Changes that alter the pH stability of HA
Changes that alter the ability of the virus to replicate once inside a mammalian cell.
The third category is the change we have seen most often and is the one I referred to as “easiest”. Upon growth in a mammalian host the H5N1 viruses seem able to make this change readily, hence “easiest”. We haven’t seen changes in category 1. There seems to be quite a barrier for viruses to overcome to make these changes. Maybe structural, maybe they need to change more positions. 2) is a bit harder to determine as we have to measure this by phenotypic assays in the lab rather than from seq alone.
QUESTION [00:02:19]
Can you discuss the thinking of why Alliance Defending Freedom isn’t planning on appealing as opposed to just litigating at the lower courts?
ERIN HAWLEY, ADF [00:02:30]
So the posture here is an emergency one. And the district court put in place a stay, not only of the 2000 initial approval, but as well, imposed the restrictions that were in place in 2000. So it really, really takes us back to those initial approvals.
And we think that is a significant win, a preliminary win, and as this Fifth Circuit opinion clearly shows, the 2000 order was not based on scientific evidence. The studies that were studied did not have the same requirements, or excuse me, the studies that the approval was based upon had other requirements like ultrasounds that were not included in the conditions for use approved by the FDA.
The Fifth Circuit has a really good example in which the court says, you know, it would be like NHTSA, the administrative agency that governs highway safety, from approving a car with seatbelts, but then later they decide, oh, seatbelts aren’t necessary, and we’re not– so that doesn’t make a lot of sense.
So what the Fifth Circuit said and what our plaintiffs have argued, our doctors have argued, is that the FDA needed to look at the safety of the drug under the conditions in which they prescribed it. Just like that, safe belts– the safety belt. And yet the FDA has never required ultrasounds, again, ultrasounds are crucial for determining both gestational age as well as ectopic pregnancies and other contraindications.
All changes that have been made to the Mifeprex label are supported by safety and efficacy data. FDA has been empowered by Congress to make decisions about what drugs are safe and effective and how they should be available to patients. Danco remains unchanged in its commitment to do all that we can to support and protect the availability of and access to Mifeprex for healthcare providers and all people in the United States.
…
We are working with our attorneys as write. All options are on the table, including an appeal.
PETER MARKS, FDA [01:19:23]
But the key pieces of this are we still will have to permanently defer people who have HIV at this time. Obviously the people for now, who have recently taken PrEP within three months, oral PrEP, or two years for injectable PrEP will be deferred. That is something that I know is there are some in the community who are very concerned about this, because obviously it will reduce the number of people who might donate.
We are going to continue to look at whether there’s a group of people taking PrEP who could potentially donate. But I think we wanted to do something now, as opposed to waiting for the six months to a year, or even a year and a half, to get this additional data. So this allows us to move forward.
…
PETER MARKS, FDA [01:20:57]
It may not be perfect yet because we still have the issue with PrEP, but I think this is getting a lot closer, and it’s as good as any place across the globe right now. The few countries that don’t defer for PrEP, ostensibly on paper, do in practice. That’s because they have oral questions that are that are done by a physician in those smaller countries such as Italy and Israel. So I think we’re right up there now with the most advanced countries leaning into how far we can go.
…
PETER MARKS, FDA [01:22:05]
So we fully expect that this will be able to get finalized in the not too distant future. Obviously that depends on our friends at the White House. It has to go through some review there. But I think we might have friends that can help us there. And I think the goal was to actually have this done in advance of Pride Month in June.
SHAWN LOCKHART, CDC [00:08:39]
So it literally just emerged on the scene starting from nowhere, in the 2009 to 2013 range. And now we’ve described Candida Auris from over 50 countries.
Now, the interesting thing is we did a look back. So a lot of countries have these large repositories of yeasts in their freezers. And we went back to these repositories. Our colleagues went back. And we didn’t find Candida Auris anywhere in those depositories. And so, it just seems to have all of a sudden appeared out of nowhere and it literally spread itself around the world, carrying on the skin of patients who’ve seen health care.
…
SHAWN LOCKHART, CDC [00:13:19]
However, some of the other machines, like the Phoenix, still aren’t able to recognize Candida Auris.
Now in in a resource limited setting, where they don’t even have any of those, it’s even more difficult. There is an agar out that seems to be relatively specific for Candida Auris. There are a few false positives, but better to err on the side of caution then than to miss it all together. And and there are some simple PCRs that that we’ve been recommending that resource limited settings can use to identify Candida Auris.
But it still is a problem. Identification is still very much a problem, because even in the U.S., only a third of hospital laboratories have MALDI TOF.
…
SHAWN LOCKHART, CDC [00:19:54]
The first cases that came to the United States could all be traced to health care abroad. It didn’t just appear here. It came on patients who had health care in other countries. So, at that time, we were not seeing state to state spread. There were few enough cases that most of them could be traced, and that when we saw an emergence in a new place, we could stomp it out fairly quickly. These patients were recognized and it wasn’t spread.
But, because it’s spreading in so many different countries, what’s happening now– we– even if we have the same number of patients seeking health care abroad, more of them are going to be exposed to Candida Auris abroad, and come back and start another chain of infection from there.
…
SHAWN LOCKHART, CDC [00:20:45]
Part of the problem with Candida Auris is when it’s carried on a skin of a patient, it’s asymptomatic, so they’re colonized, and there’s no reason for a clinician to suspect that their patient might be colonized with Candida Auris, aside from having health care abroad. So if it’s not suspected and identified right away, it’s transferred to other patients in a facility. And you can see quite a bit of spread of Candida Auris before the first patient comes down with an infection which is recognized.
So Candida on the body in non sterile body sites is usually not identified as species. That’s just not something hospitals do, because we all have Candida. And so it’s only after the first infection that it gets recognized. And then there’s a look back, and you discover that, 10, 12, 15 patients in your facility are colonized.
…
SHAWN LOCKHART, CDC [00:23:33]
Cleaning surfaces and and equipment because Candida Auris spreads, we believe, through dry skin. It’s shed from the skin. And when you’re in a hospital environment, you’re getting these harsh detergents to deter, say, the gram negatives and things that find their way on the skin after long term health care. So you get these harsh detergents, your skin gets flaky, the flakes contain Candida Auris, and an entire room can become covered in Candida auris. We found it on on the beds, on the bed rails, on the sinks, on the windowsills, on the floor. One case, they even found it on the ceiling.
Equipment is another place, primarily because not only is it coming off the patient, but equipment is often touched by, you know, nurses and doctors. They’ll come in, they have gloves on, of course, but if they touch the patient and the patient’s colonized and they touch equipment, it can go.
So, in rooms where we have Candida Auris patients, you need to have very good infection control practices, proper PPE, and you need to use the right kind of disinfection disinfectant. Not all disinfectants work against Candida Auris. So the, the quaternary ammonias, which are your Lysol type compounds, a lot of health care facilities use that, use Lysol and those other quaternary ammonias. That doesn’t work against Candida Auris.
You need bleach and bleach based disinfectants or combination disinfectants. No one wants to use bleach. Bleach smells bad. It’s corrosive. But, you know, that’s what it takes. And we’ve worked closely with the EPA. They have a brand new list. It’s called List P. You can go to the EPA website and look up List P, and those are the disinfectants that have been shown to be effective against Candida Auris.
DEMETRE DASKALAKIS, CDC [00:51:10]
We keep pushing the envelope. I mean, I know that wastewater, as an example, in COVID, has been really interested. In polio, it made a big difference, right. And then now in mpox, we have it. And you have not lived until you launch like a new kind of surveillance and a disease are new, right? So literally, like we have this surveillance, we made it maximally transparent. We’re like, we are doing wastewater for mpox, and it goes online, and everyone can see it. It’s updated once a week. And then the next question you ask is, then what are you doing about it?
So we’re all learning together because, and it’s been fascinating. And this is like– this is a little bit off the topic. But, we have one jurisdiction right now that shows consistent detection and zero cases reported in the lab. And so you have not lived until you see this unfold in real life, to sort of see how like a local jurisdiction works with CDC to figure out like what they’re going to do, what are the best practices, and is there going to be a protocol that’s going to come from it?
Thinking like in a public health mechanism, like we’re totally going to get an SOP out of this in terms of what to do in this situation.
ROBERT CALIFF, FDA [00:05:26]
The first point is every boost that we’ve done so far has resulted in best estimate 80 to 90% reduction in death and hospitalization over and above what had been achieved with the previous boost before that. We’re now out where most people who are– were up to date with the last, the first bivalent opportunity, are now getting six months out.
I’m 71 years old and I’m about seven months out now. I think I communicated with you, I got infected about two months after getting my vaccination. So decision making is a little complicated, but, you know, we’re planning– it’s well known based on the advisory committee meetings that we’re planning on doing something major in the fall. And the question now is, do we do something in the interim?
And all I can say now is we’re looking carefully at the data. It’s obvious from the timing that decisions are imminent, but can’t make the news today of saying what the decision is.
…
ROBERT CALIFF, FDA [00:06:47]
Well, I don’t want to sound cynical, but, you know, I grew up in academia where rumors abound, just like they do everywhere else. And certainly in the world of Washington and the press. It’s– the press is under tremendous pressure to break news, just as you were just trying to do.
And you’ll find that leaks half the time are leaks of real truthful information. Half the time they’re intended to cause a stir, a fire off somewhere else, to take people’s eyes off the issue that’s really in play. And I can’t say which one this is. We’ll find out soon.
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ROBERT CALIFF, FDA [00:08:48]
And you’re right, in normal times, the FDA should not be a cheerleader. The FDA is a referee calling balls and strikes or shots before or after the clock, something I’m still paying by with the NCAA tournament. But in this case, we’re in the middle of a pandemic. People are dying at very high rates. And in this case, we actually had a phase three trial that showed this dramatic reduction in death and hospitalization well over and above vaccination. And we were able to see data because of the magnificent job that Israel, in particular, was doing, of collecting real world evidence that showed that it wasn’t just an artifact of a phase three clinical trial, it actually was being borne out in the real world.
So I felt I had an obligation as a public health official to point out that the evidence was strong. Also remember that with an EUA, the company can’t advertise and the purchasing is not done by sales reps selling the hospitals and p,ractices its bulk purchasing by the government. So I felt we did have a public health obligation to make it clear to the public and to hopefully to practicing clinicians, doctors and nurses and pharmacists that the people who are dying, by the time we add vaccination and antivirals, almost everyone who is dying or getting severely ill was not up to date on vaccination and had not been given the opportunity to take an antiviral. So that was what was driving me.
I think in the time of a pandemic, you have to make a lot decisions, more like being an ICU doc than it is a doc is in a situation where you can give advice and have the patient come back three months later. You got to make decisions. You’re going to be wrong some of the time and criticism is fair. I feel like I was right in this case.
…
QUESTION [00:28:40]
Would you say the amyloid changes in the amyloid is an example of an unvalidated surrogate marker?
ROBERT CALIFF, FDA [00:28:46]
Yes. Yeah. Although, by the time all the data is in, I think this year we’ll have enough outcome data and intervention data to make that determination.
QUESTION [00:28:59]
I guess it’s tricky if, let’s say, I mean, determining that a surrogate marker is validated, if the drug lowers amyloid and turns out to have a beneficial effect on Alzheimer’s, I don’t– It doesn’t prove that the next drug that lowers amyloid will have a beneficial effect. Could be–
ROBERT CALIFF, FDA [00:29:17]
Say let’s say you have six drugs that lower amyloid and all six you draw a plot of delta clinical measurement of Alzheimer’s state, whichever measure you’re using, and delta amyloid, and they’re on a line. That would tell you got something there.
So I think everyone’s now familiar with the blood pressure and LDL cholesterol levels, where you have multiple treatments, and depending on the delta LDL, or the delta blood pressure, you have a commensurate change in outcome. That’s the question.
QUESTION [00:29:52]
Yeah, but it really requires multiple tests to be sure that it’s not just a single drug that maybe has some other effect that you’re not measuring?
ROBERT CALIFF, FDA [00:30:02]
Let me just say one other thing that people should realize is there, and I want to say we welcome criticism at the FDA. Just keep it collegial and in bounds, please.
But, remember that the FDA is looking at everything that’s in the field, including data from companies which are not yet able to publish their data. And in fact, one of the problems that I’ve worked on my whole career, and I’ve not succeeded, is that all the drugs that don’t make it, there’s no obligation of the companies to make all that data available. And so the FDA is looking at a lot more than what you’re able to see in public. And by law, it cannot release commercial confidential information. There are actually criminal penalties for a person that works at FDA who does well.
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ROBERT CALIFF, FDA [00:38:53]
We are having a lot of interesting discussions about that. And as you might imagine, they range from how do we regulate it to how do we use it?
I mean, you think about the work of an FDA reviewer. There’s a lot of sort of are those writing guidances and policies that there’s a lot of searching around to find what’s out there and what’s been written before.
You know, we had just as an example, where have had a vibrant discussion: there’s a term called grandfathering, which is now no longer acceptable. The problem we have at FDA is there are hundreds of guidances and rules that have grandfathered– the term grandfather in them, and it’s used in different contexts, which means you got to go back and find it to change it.
There are just so many amazing opportunities ahead. Just like, I think for your clinicians, the ability to summarize the past history and notes and all. It’s going to be revolutionized.
But I think this pause that a lot of the leaders have called for in the large language models, big experiments, there’s something to that. And I’m relatively certain we’re going to have to have much more quick regulation at a higher level than I had thought, prior to the large language model exposition, because this stuff really does get a life of its own. And it’s very hard to tell what’s truthful and what’s not and when it’s out of control.
So I want to give credit here to CDRH which, way back put out the idea that the pre-market part of algorithms is really the small part. The big part is, once it’s out there, there’s got to be a system for auditing and updating its quality, using tools that we understand pretty well now. How to do that with large language models, I think it’s going to be quite a challenge.
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ROBERT CALIFF, FDA [00:45:52]
The number one thing we can do right now is to flood the world with Narcan and I relate to this easily because, like I said, defibrillation got me started on cardiology.
You don’t get charged for a defibrillator.
You know, if you drop over dead, you’re going to get a defibrillator if there’s one handy, and we’re trying to make one handy everywhere.
I think Narcan needs to be the same. So over the counter Narcan is just one of many things that we’re doing.
Little known fact is the majority of Narcan now is actually distributed by harm reduction groups, which are public health groups that get it in bulk and essentially give it away.
But, the wrinkle on Narcan over the counter is that if it’s over the counter, CMS can’t pay for it. So when you consider insured people, it may make the price go up.
So we’ve had to do a lot of work to deal with things that we hope other people don’t have to think about that are sort if in the back room. So that’s that’s a big deal.
…
ROBERT CALIFF, FDA [00:53:37]
All I can say is that over 20 years ago we evaluated the risks and benefits of mifepristone and concluded that the benefits outweigh the risks for the intended use and over the 20 years, the scientific assessment hasn’t changed. Those decisions are made by full time civil servants. Their opinion hasn’t changed. So the science and the medicine remain the same.
I can’t comment on the court issues because it’s under litigation at this point.
HELEN BRANSWELL, STAT [00:27:46]
My question is regarding the Marburg outbreak in Equatorial Guinea. Any information on updated numbers would be good and also has the country agreed to conduct or allow clinical trials to be conducted? Or has it said, no? Thank you.
ABDI MAHAMUD, WHO [00:28:19]
In terms of the epi, as you may can imagine, these are evolving epidemiology and with time, we may have new cases. But as of now, we have 14 confirmed cases and 23 probable cases.
Of course, with data, investigations, the number may be shifting back and forth. What’s good is the number of the system built over the last few weeks. The contact tracing has really gone up. Almost 555 contacts are being followed and follow rates around 90%. The country is still struggling with alerts. The alerts are around 2 to 6, where we expected double digit number.
In terms of research, as you can imagine, our– at the highest level of the organization from director general to the regional director, to our WHO representative, have been engaging with senior government at all levels since the start, as we believe very importantly, what we learned from the past outbreak, integrated research is very critical.
As for now, the country is really looking at that. They are considering the status of various elements, building the basics of contact tracing, alert, laboratory. And what we are told right now is, when the conditions may be favorable, the trials may be initiated. And so right now it’s building the basics of good alert management and case management and other basics of the outbreak response, and at a further future date, may be considered.
But as of now, we don’t have a firm date when it will start. But the government gave us on Monday the good news that WHO experts can arrive on visa, can receive visa on arrival. So we are getting more positive and positive engagement from the government and if the basic elements of the response were established, we believe that the government may consider this favorable. But as of now, we don’t have a firm date when we can start.
From WHO side, as we said in last week, and the previous, we are ready and we appreciate all the partners and all the government and all the stakeholders who have been patiently waiting when this trial will begin.
MAYORA WALTERS, CDC [00:09:39]
During summer 2022, three different health department programs reported facility clusters of Pseudomonas producing the carbapenemase bim. The first was highly unusual because it was at an ophthalmology clinic and it consisted of the first carbapenemase producing pseudomonas from eye infections that had ever been reported to CDC. The other two outbreaks were at long term care facilities in Utah and Connecticut.
Because of the increased capacity for whole genome sequencing, CDC has advised public health laboratories to routinely sequence carbapenemase producing pseudomonas. And while looking at sequences for one of these outbreaks, we were able to determine that all three outbreaks were caused by the same strain, and also found isolated infections in two additional states.
…
MAYORA WALTERS, CDC [00:12:58]
So as of March 14th, we had identified 68 patients with the outbreak strain. These patients were from 16 states and 37 were part of 4 different facility clusters. They had a median age of 61, but ranged from less than 1 to 102 years old. Their cultures were collected between May 2022 and February 2023 across a variety of clinical settings that included acute care hospitals, long term care facilities, and outpatient clinics. And patients had many different specimen types.
38% were from surveillance sources identified through colonization screening, 26% from eyes, and 35% from other clinical sources, which included urine, sputum, blood and a few other body sites. Next slide.
…
MAYORA WALTERS, CDC [00:14:46]
So this slide shows patient outcomes for all patients on the leftmost column. And then among the subset that had clinical cultures in the right two columns.
60% of patients had a new hospitalization related to their culture. And among those with cultures from sites other than the eye, 55% went to the intensive care unit. Three patients died, including one with bloodstream infection and one with an eye culture. Among the patients with eye infections, eight had vision loss with the eye preserved, and four underwent enucleation, which is surgical removal of the eyeball.
…
MAYORA WALTERS, CDC [00:15:39]
We conducted a case control study at a long term care facility that had the most cases and found that cases had a five times greater odds of exposure to artificial tears than controls. This was noteworthy because none of the cases at this long term care facility had eye infections, and was relevant in light of another cluster of eye infections.
We were unable to differentiate the exact brands of artificial tears received by most patients at this facility. But ultimately, we were able to determine that EzriCare artificial tears had the largest purchasing volume of any brand, and so that many patients at this facility who were receiving artificial tears likely got this product.
We were then able to narrow in for the other facility clusters on artificial tear use. We now had four clusters, including two with eye infections. We determined that EzriCare artificial tears was used across all of the facilities and, among patients in this cluster, 76% used artificial tears and 85% of those used EzriCare. For the 31 patients who were not linked to clusters, 63% used artificial tears, and among those, 69% reported using EzriCare, including all eight patients who had eye infections.
EzriCare Artificial Tears is a preservative free formulation that was dispensed in multi-dose vials and distributed nationwide over the Internet. It was manufactured in India. Next slide.
Using the epidemiologic evidence, we were able to gather up and product through our high programs. And CDC ultimately tested 23 open bottles from 5 lots in two states. 11 showed bacterial growth and the outbreak strain was identified in 7 bottles from 4 lots in 2 states. Now, testing of open product cannot differentiate between intrinsic contamination and extrinsic contamination. And so FDA is testing unopened bottles of EzriCare currently. Next slide.
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MAYORA WALTERS, CDC [00:24:32]
About how can an eyedrop cause, for example, a bloodstream infection? And so there’s two pieces to this question.
First, certainly we know that the tear ducts are connected to the upper respiratory tract and the lower respiratory tract. And so that you can imagine if patients are receiving artificial tears, especially patients who are already quite sick, who are perhaps mechanically ventilated, they’re in long term care facility, that that bacteria is eventually going to colonize the airways and from there potentially colonize the digestive tract. And we’re going to see infections at other sites. So I think physiologically, there’s a plausible explanation for that.
There’s also the piece of secondary transmission, right. Not all cases in this outbreak received artificial tears, although we think that is ultimately the source of this outbreak. And that is because we know that there is person to person transmission of this organism. And in fact, historically, that is how we have seen this spread. And so there is also the fact that some of these patients probably got this organism from other patients and essentially got infections because of whatever their risk factors were for infection at a certain site.
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MAYORA WALTERS, CDC [00:26:06]
And I think that’s what we really saw with the the case control study. Right? Is that we saw an association with artificial tear use, and we actually saw that most patients in the facility did not receive artificial tears. But there were some instances, patients that we suspected actually were secondary transmission, did not receive artificial tears, but had a clear link to another patient.
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MAYORA WALTERS, CDC [00:34:50]
The first question was about cases from around the world. And so I do want to just clarify that, no, we have not had other cases reported. And while Global Pharma is, our understanding is that they are a contract manufacturer, and provide services to many countries, our understanding based on the recall, is that this product was only sold in the U.S. and so that’s consistent not seeing those cases.
And then this particular strain, with the carbapenemase VIM-80, the GES-9, that combination of features had not been seen anywhere. So I think we can’t comment on how common this is in India. We do know that there are reports from that region of isolates both with VIM-80 and GES-9. But really we couldn’t use the the molecular information to deduce where this might be coming from.
We do know that there are reports of carbapenemase producing organisms in the environment in India, and based on that, we hypothesize that the source of this outbreak was probably an environmental source in the manufacturing plant. We don’t have more details, though, on how exactly this became contaminated. And it is a question that we would like to know more about.
PETER MARKS, FDA [00:06:38]
In the blood end of things, through the pandemic, a study was conducted looking at whether our donor deferral policies for men who have sex with men could be modernized to use individual risk assessment rather than time based deferrals. This study was, I think, actually groundbreaking in that it was developed by a combination of government advocacy organizations, academics and blood collectors working collaboratively to look at what might be a relatively simple individual risk assessment questions.
Without going into the details of the study, it was intended to enroll about 2,000 individuals, which was very– proved very challenging during the pandemic. This study started right as the pandemic was really coming into full force. Ultimately, it’s now finished enrollment. Although only 78% of the 2,000 individual goal was reached, that is enough to provide us with the information that we needed, in part because we modified the study so that, rather than only having extended follow up interviews in about 200 to 250 individuals, that was increased to 1,200 individuals. So a tremendous amount of information coming from this.
That information should be available online in the not too distant future in a pre-pub, and it’s being submitted to a major journal for publication at the same time.
What this has led to is issuance of a draft guidance for an individual risk assessment policy, which would allow the same donor deferral questions to be asked to people of any gender as they come to donate blood. So again, a policy issue there obviously, that will go along with this, too, will be potential changes in other parts of our world, potentially even in the world of cells and tissues. But that’s for another day.
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PETER MARKS, FDA [00:17:51]
And so these– our budget authority has been taxed somewhat here. On top of this, other areas where we’ve had some demands have been keeping up with the type of surveillance that we’ve needed to do for the vaccines that have been deployed.
Vaccine safety surveillance is a very expensive endeavor, because use of these large database systems is quite is quite expensive.
So I think our budget has done reasonably. Can’t complain horribly. But we have not had really major increases.
And so we’ll we’ll we will make do. But this this is a challenge as we need to hire up. It’s a challenge also because as we hire up closer and closer to our headcount ceiling, what we lose is the under burn in our budget that helps actually support some of our endeavors in our labs. So we’ll have to balance that.
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PETER MARKS, FDA [00:19:04]
I think the new demands we’re facing over the coming year are going to be ones of, first of all, being able to continue to recruit and retain in this new environment which is very challenging. That goes without saying, but we are going to also have to keep up with the safety surveillance on the vaccines as well as on the various new products that are going to come across the finish line. And I suspect there will be any number that we’ll have to initiate safety surveillance on. So a fair amount there.
We’re also trying to continue our work in advancing manufacturing. That’s both important for cell tissues and gene therapy as well as for vaccines. And that work also is something that is important to be continued if we’re going to stay ready for future pandemics.
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PETER MARKS, FDA [00:20:11]
This issue of staffing and whether we’re staffed to a level of that’s appropriate for our critical public health mission is a really good question. You know, we the good news is right now we have the assigned headcount and we need to fill it. The bad news is it’s challenging to fill, because some of the most high priority staff to attract, which include CMC reviewers, statisticians, epidemiologists, are in high demand elsewhere. It turns out that you know that if you’re a statistician or even epidemiologist, those skills are highly valued at internet companies, whether or not they’re related to health care or not. And so that has been somewhat of a challenge in the area.
But those are really high priority hires for us. Not to say that we don’t consider it a high priority to fill a lot of the other vacancies for medical officers or other review staff.
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PETER MARKS, FDA [00:26:22]
Even though the 21st century cures salaries are good and they’re– it’s a great– I mean, I am very grateful because without them we would be smoked. Sorry to use that term. But unfortunately with really good people, and the industry where it is now, there’s a lot of opportunity. And the new economy where people can switch jobs without having to physically relocate, it’s to our advantage, but it’s also to our disadvantage. We’ve used it to our advantage to be able to recruit some people who could not move immediately. That’s great. Unfortunately, it also means that some of our people have been picked off to to go elsewhere.
So I think our recruiting challenge is trying to make what we do attractive enough so that we can recruit people for the salaries that we can pay, which means we have to be a workplace of choice. I think that means that to the extent that we have an organization that empowers people as much as we can, that’s a diverse one that people really enjoy working in. We have to use all of the other tools, the soft tools that go along with the salaries, and we intend to use them to a max.
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PETER MARKS, FDA [00:41:34]
For the vaccines we have, although we don’t typically think of FDA as the purveyors of vaccine confidence, I think we have to do our part in helping to simplify, clarify what these vaccines do and how they will work, work with manufacturers to make their administration as simple as possible, potentially by working towards combination vaccines that will help for vaccinating during the winter times. So there’s a lot to be done here. AndI think it’s going to mean a lot of work over the coming few years.
I don’t think– I think although COVID is going to end as a public health emergency, the amount of work that we have coming off of this is actually quite a bit, because these emergency use authorization have to turn into biologics license applications. That’s a lot of work. EUAs were much easier to deal with. They did not require the same type of manufacturing inspections, and the same type of review and evidence requirements as will these supplements. So we’ve got a lot to transition.
We’ve got to look at the next generation of vaccines coming along, hopefully a better generation in the future. But in the meantime, just keeping up with what we’ll need for annual vaccination for next year.
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PETER MARKS, FDA [00:43:07]
And then at the same time, we’re doing all of that, we’re going to have to keep our eye out on what might be next and whether that is an influenza pandemic or, we have H5 lurking in the background, bird flu, but others as well. So we have to not let our guard down here and be ready for this. But that, I think, that that’s a lesson from COVID 19 here. Right? Is that we need to have readiness for what may come along.
And I think that’s something for our center that we realize and it may be so, it gets to one of the areas that we may want to think about moving forward, is how do we staff up in our office of vaccines so that we don’t adversely impact the day to day vaccines when we have the next outbreak? I mean, it would it just it’s just right now the way we were able to to actuate Operation Warp speed was by essentially pulling people from other projects. And we all need, I think, in the future to think about ways to avoid having to do that.
PETER MARKS, FDA
[00:13:15]
Having lived through influenza mismatches, I think we’re unfortunately in a situation where one would be a bit not realistic to think that it’s going to be a challenge this year selecting what we need to select for next year. It’s not, at this point in time, because of the manufacturing delay, of about 2 to 3 months between at least the mRNA vaccines and probably three or four months for other types of vaccines, at least, we’re going to have to pick something in come June-ish.
[00:13:51]
And it’s not clear that there’s something new besides what we have circulating currently and what’s dominant to pick. And what we know about that about SARS-CoV-2 is that it likes to do these funny things, particularly when you have susceptible people and not susceptible people, and we may have a variant that will come out, that will emerge over the summertime that may become dominant that might not be as well neutralised by whatever we think.
[00:14:25]
The good news, though, I think this is I think encouraging thing is that hopefully we will prevent severe disease or boost protection against severe disease and hospitalization like we have in the past. And I think, you know, if a key learning perhaps has been that not to oversell vaccines for for what they are. If they’re preventing hospitalization or death, that’s a good thing.
[00:14:53]
And yes, it would be nice someday to have a sterilizing vaccine that prevents transmission. But I’m not going to hold my breath because I think it might become very blue in the face.
[00:15:13]
And people have done that for influenza for ten or so years or and we still don’t have that one. So I think we just are going to have to do our best here and make sure our messaging is correct, that we may or may not get it right on. But even if we don’t get it right on, I think the chances are more likely than not that we can provide or at least protect against severe disease and otherwise, we’ll have, in the event that the unthinkable happens, which is that some bizarre reassortment occurs with SARS-CoV-2, we’ll be probably looking to the mRNA manufacturers to make something as fast as possible to deploy and as quickly as possible, much the same way as we have to do if there was a pandemic flu strain.
[00:16:09]
So that, I think, is what we have to just have in the back pocket, which is why I think the mRNA vaccines have been a nice thing to have the back pocket. And also this has been a good time to think about other vaccine technologies and how you speed up further the manufacture of vaccines with those other technologies.
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PETER MARKS, FDA
[00:20:43]
So I think we’ve done a fairly good job, I think, of trying to have conversations back and forth with our our EMA colleagues. We’ll continue to do so. We might not be 100% aligned, but I think last year we got pretty closely aligned, and I think– I think we’ll continue to try to do that.
[00:21:08]
I think actually getting aligned with EMA colleagues is somewhat easier than perhaps being perfectly aligned with the larger WHO, which I fully acknowledge has a different mandate in what they’re trying to do. But as a high income country, I think with like minded countries, I think we’ve done a reasonably good job aligning and we’ll continue to try to do so.
[00:21:32]
I think the more we can help with alignment, the better we will be. Because something you said your opening remarks was also true, which is that to me, the greatest catastrophe of COVID has actually not been any kind of a miracle, which is vaccines remarkably quickly, but a catastrophe in the erosion of confidence in vaccination as a major public health tool. And I am very concerned that we continue to see this. And it seems like throughout the pandemic dwindling, that sentiment seems to be building.
[00:22:07]
And there seems to be a field effect not just for COVID vaccines, but for other vaccines. And so I’m hoping that we’re able to somehow stem that tide by good– by essentially truth in advertising and trying to just continue to tell the truth about these vaccines and what they’re capable of doing.
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PETER MARKS, FDA
[00:39:08]
This was not something that was sustainable and there were casualties along the way. And so I think as we think about this, I think it’s a matter of thinking ahead. I think we are hoping that we start to staff up to the point– I think we have– we have a new– I think we have a new normal now, which is that if you’ve looked over the past years, if we’re not having a pandemic, we’re having some epidemic or outbreak, that’s pretty serious. I mean, we dealt with Ebola, which because of the number of people it was killing, and because of the risk of it breaking down further, we took very serious at the time. So that was a very large undertaking.
[00:39:54]
So I think we’re going to be thinking about staffing up to a place where we can accommodate the need, and may not be perfect, but accommodate the need to have to mobilize quickly for whatever new pathogen comes along without having to completely disrupt the rest of the functions. And that may mean that there’ll be staff that in the interim between the pandemic period or endemic period, they’ll be working on helping to provide advice for other vaccines. Department of Defense has plenty of vaccines that they can use some help with, and they can help with those types of things and others.
[00:40:36]
So I think having that excess capacity is going to be critical because this is, I think, the new normal.
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PETER MARKS, FDA
[00:40:43]
And I do worry, and this gets into another piece, that part of the reason why we have to continue to advance our manufacturing capacity is because we have to be ready for the next thing besides coronavirus, where getting manufacturing mobilized is really a key thing.
[00:41:03]
And we’ve learned some really important things from this outbreak, which would be a mistake not to remember, which is that cold manufacturing facilities are basically worthless. You need to have warm capacity, with trained people, to be able to ramp up quickly. So I think that’s a lesson. So having warm manufacturing capacity, more reviewers at FDA, is kind of the recipe to do this better next time.
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PETER MARKS, FDA
[00:42:38]
I want to start by saying, I think, to quote someone in the audience here who always says, you know, everything remains on the table. Everything remains on the table. And I think we should be using all the different vaccine platforms at our disposal and not dispose of any of them.
[00:43:00]
I think it’s a matter– there are benefits and risks that we’ve learned and maybe we’ve learned from, from vaccinating millions of people, we found some of these platforms have risks associated with them that we might not foreseen. But that doesn’t mean that we shouldn’t be continuing to use the various viral vector platforms and protein based vaccines and the whole gamut.
[00:43:25]
Because the best vaccine is the one that can get into people’s arms. So if people have problems with mRNA for some reason or another, I really don’t understand myself, but they do, it’s nice to have alternatives and it may turn out that there may be adenoviral vector of other viral vectors that turn out to be excellent at bringing us long term immunity because look what they’ve done to date.
“Sanofi does not have a product shortage issue for TENIVAC.
According to CDC, an interruption in the distribution of TDVAX occurred between December 2022 and early March 2023. Sanofi is working with CDC to proactively meet market needs in a responsible manner by increasing the supply of TENIVAC during this period.
We continue to monitor the situation until the supply of TDVAX returns to normal. In certain cases, this does mean that we put controls in place on the ordering of our TENIVAC in this temporary situation.”
Grifols, committed to ensuring patients receive the treatments they need, is currently making all accessible TdVax available after a temporary interruption in supply from the manufacturer.