Our final speaker, Mr. Warf, comes from BARDA
and he will share with us his experience with Ebola response
and permitting process.
Thank you.
>> Well thank you very much for inviting me to speak on this.
I'm the only person that doesn't approve permit,
have anything to do with a permit.
I am not actually even an end user having to do permitting,
but I represent that group in many different ways as part
of the US government public/private
partnership routine.
Because I partner with many, many other companies
as they try to do things.
And our latest and greatest activity
on this has actually been the Ebola response.
Now this presentation is going to be really different,
because I'm going to spend probably 90 percent
of it setting the stage about what it was like back
in the fall of last year
as we were really gearing up to deal with this.
And then somewhat talk about what happened
and how convoluted the permitting process is.
I think that's been explained pretty well today.
And then how we try to execute it
so we can actually move pretty quickly.
Because if it's not obvious to anybody,
the permitting process works real well, but it is not a just
in time kind of process.
You have to plan, you have to submit.
You have to do a lot of things ahead
of time besides just understanding the regulation.
So just for a good graphic everybody sees
to remind everybody what was going on,
that nice pretty picture in the middle is
of course an electron scanning microscope
of what the virus looks like attached.
So when it happened, BARDA was in a unique position
to be coordinating a lot of the activities going on.
And this slide gives a summary
of all the different places we had activities happening,
either in the manufacturing realm,
in the product development realm,
filling of the material realm.
And then everything's going down to those little stars
in the bottom right-hand corner.
So you can see that there's a lot of transportation and going
in and out of national boundaries
that is part of this activity.
And so it's really pretty important to understand
that as this was going on,
if you remember the wonderful new cycle that we were under,
there was a lot of just in time activities
because they were trying to find an airplane
that can carry a patient someplace
from one country to the next.
So this is what's going on and all the counter measures,
i.e. the possible therapeutics that might be given
to the patient, or some of the stuff that might be used
to protect the staff for part of this.
And that's what I'm going to talk about, is more protection
of the staff than the actual countermeasures,
but I'll have a little bit of both.
So if you want to look
at how many different government agencies
and how many other groups are involved, this gives you an idea
of how many different groups were playing with this process.
And it's a lot of folks.
And it's a lot of coordination and there are a lot of depth
in places like the NIH
where it's multiple pieces of the agency.
And then there are a whole bunch of other people
who are looking at it and evaluating.
And these are all over and above what happens
on the permitting cycle.
Because you see it says CDC is part of this, but guess what?
It wasn't the part of the CDC that's actually directly
involved with granting permits.
So it was a unique thing about how to get all the pieces
of the puzzle put together.
And I would like to point out, as Jessica has talked to us
about what it's like to deal with other countries
that are not listed, I would like to point
out that the governments on the bottom are not listed.
Fortunately, many of the agencies actually carrying
on the activities or clinical trials were government agencies.
So it was going from the US government in the United States
and we had actually distributed into the embassies
so that the embassies had control.
I want to say we didn't skirt the regulations.
We actually took advantage of those regulations.
And we kept very good control of what was going on.
Although the exception to the regulation
about it could be used for a declared emergency like Ebola,
we kind of managed on that one too.
But there was a lot of good coordination that took place
and you could see how many different groups had
to be coordinated with this.
So when it kind of go kicked off, there were a lot
of companies that thought they had vaccines
that could apply for this.
This is kind of the midlevel, but at the very beginning,
everything was in preclinical development.
And so when you are confronted with,
"We want vaccine yesterday," and you have vaccines
that we don't even know whether they're safe to put in humans
or not, it really does lend itself to a crash course
of how you move things around and how things go on.
Now I will be concentrating a little in my talk
on this experience, on actually the one that's listed
on the far right that says New Link Merck.
And that was an RVSV Ebola vaccine
and it is a live virus vaccine.
A little more specifics on it.
But in the end there were permits required
from the CDC, from the USDA.
Of course going around in the clinical aspect from the FDA.
The only people I think I miss
and then aren't represented today are actually the
wildlife guys.
We do have vaccines that fall under Fish and Wildlife also,
so it's just a real mix of what's going on.
But you can see there were a lot of people.
There was a lot of triaging.
Many of the vaccines listed here were put in clinical trials
and we moved them around, or were going into clinical trials.
So there's still a lot of movement even to this day
of the permitted vaccines in and out to the various countries.
So in the VSV vaccine, you can look to what it was applied
to in this particular place.
And I want to really emphasize
that it was the post-exposure prophylaxis that was considered.
There were some nonhuman primate clinical trials that were done
that indicated that if you had some reason
that you thought you were exposed and you caught it
that first day, first few hours that you thought it happened,
you could actually be vaccinated.
And there was a strong indication
that the vaccination would provide you some protection.
So that's really important to many,
many of the healthcare workers that are involved in taking care
of the patients as they moved into the United States.
That one piece, even though that's not a therapeutic,
even though it was not being given to any of the patients,
was still an important aspect about how we moved our materials
around over and above what was actually given to patients.
So in that particular aspect,
this is what it was used for particularly.
It shows that if you got the exposure at that day of,
you could get a dose of it and you might be protected.
I still would like to emphasize they had some data
to indicate this.
But this wasn't a proven and it still is not a proven vaccine,
although it's doing very good in the CDC trials at the moment.
So when you look at the other side of the picture
of what could you have given somebody besides this vaccine,
what therapeutics were there?
The list is actually bigger at this point in time.
Back in that early fall time period this is what was
on the line.
And all of them were unproven and all of them were
in pretty short supply.
And just as an aside, we would like to understand this,
if you look down at the bottom middle of the page
where it says bio, you look
at those three different why things.
Those are the three monocle antibodies.
It actually takes three different components
to successfully administer the therapeutic.
That has so far been the most tested down the line
with success, although it hasn't been proven yet.
All the time we're trying
to manage all the vaccines going on, we're still also trying
to manage the movement of the therapeutics
and where they're going and how to manufacture them.
And so since this had so much play in the press,
I thought it was worthwhile giving everyone a quick look
at what was going on and how we did it.
And this again, we were working very hand in glove
with how we helped the manufacturer or partnered
with the manufacturer in their relationship with the FDA
so that as things took place, the IND's were
in place correctly and set up correctly.
It was set up so that Jessica's team knew we were going
to export it and where it was going.
So there was a lot of real close coordination
of how these things took place.
And as we begin to really push up into clinical trials over
and above the reactive side of it
where we were helping individual patients.
So let's get down to the final part of my story.
So one night it had decided,
I think there was a joint telephone call with lots
of people in place, that they were going
to move a patient to Emory University.
Now between the decision to move them and the actual movement,
and I believe that's the good doctor
down in the bottom right hand corner.
Between that point in time some therapeutic was actually
administered in country.
And then the second part of it was that Emory University
and all the people got together and said, "Well, we really would
like to have a PEP, post-exposure prophylactic,
vaccine available for our staff."
Because they didn't know what was going to be going on
and how that needs to happen.
So this is a sequence of all the things that had to take place.
The actual vaccine was in Canada.
Go figure.
It was actually made in Germany.
That makes it even more complicated.
So the vaccine had to get from Canada into the US
down to Emory University.
Now there's only eight doses,
so that nice thing Mr. Stevens showed about how you plug it in
and put it in this nice little box.
We're not talking about a huge movement and huge container.
But it's still not exactly
like your standard FedEx package perhaps.
In addition to that, we also had to get all the alignments
in place for the doctors that were going to be managing it
so that they actually could follow the IND
and the clinical requirements for a vaccine
that just had its IND submitted the day before.
Well, I take that back,
it may not even have been submitted by that time.
It was actually a provisional one.
I think Jessica is nodding her head on that one.
So anyway, so there were a lot of people
who were giving their check off on this one.
So when it handed out, it was coming to a company
that had just established itself, Newly Genetics.
So Newly was trying to figure out how to put permits together.
Now all the people here who are in the permit business know
that a brand new person putting a permit in is not going
to be the best filled out permit
and exactly what we are going to be looking for.
Fortunately, it at least was going
through a well-known carrier who was World Courier.
This is not a plug for them, but that's who was bringing it in.
So they at least had a good understanding.
They shipped this in some extent all the time.
So we were trying to educate a new company to submit permits
to both the USDA and the CDC.
We had to get their people also coordinated with the FDA.
So all this took place.
And then it had to come across the border and go through CBP
with all the right paperwork.
And then all the local areas looking
at the paperwork correctly.
For this particular activity we ended
up porting it three different times.
It went through three different border points
and it didn't work any of those times.
And try as we did to try to notify people ahead of time,
send emails out to everybody, it's a tricky process.
And the paperwork is not necessarily complicated,
but it is not easy either and there's a lot of it.
So it was very interesting, but the real thing that happened,
and the comment about when you have something going and it's
that data input at the time.
50 percent of our problem was mis-entry
of data and figuring it out.
Because CBP doesn't have the right person to call
when they don't see it going wrong.
They talk at the local level to the freight forwarder
and that information takes a long time
to filter back all the time.
You've got the doctors down in Atlanta saying,
"Where's my vaccine?
What's going to happen?
We're going to have a patient coming in soon."
So it really makes for a very exciting couple of days
and a lot of phone calls.
Now this was before I knew about Von
and the tiger team had been put together.
So there was a lot of phone calling
of just various individuals in this, not as a group.
Now after this there was a lot of pushback
from upper management, government upper management,
you can take your guesses at whom,
about how we would make this work a little better.
And actually the tiger team
that now exists is probably the best representation
about how we do that and how we filter information.
So the whole time we're getting Emory going it is decided
that we need to have a safety trial for this same vaccine,
and that's being handled by the Walter Reed Army Institute
of Research called RAIR.
And so the next step was trying to get sufficient vaccine
into them to allow them to do that.
And here we go again, it is a vaccine coming
from Germany that's in Canada.
So every time something happens there was a new wrinkle
about a piece of paper.
And fortunately one vaccine hit one border crossing point
and we were able to get back to the German manufacturer,
IDT in time for them to put their certification
of how it was inactivated on the letterhead and shipping it.
It was classic.
But we finally got in and all the paperwork went together
and we never lost any product,
so I guess that's the real aspect of the regime.
It just creates a lot of heartache for people
as it moves in and out.
So that trial also came in.
We managed to get it.
It was all handled in Washington,
DC and it actually turned out to be very successful
and things were going along.
Now if you remember about the news going on,
we begin to have more patients that need to be taken care
of than we had space at Emory and at the NIH.
So the University of Nebraska set up to do it.
Now this is the first time they have actually been involved
with this, so again we have a whole series of activities.
Fortunately most of the vaccine has now gone past Canada
and is in the US.
But as was pointed out by the USDA, you still have
to have a transport permit if you're going to move it
from someplace in the US to someplace else in the US.
And it still needed a CDC permit even though it wasn't an import.
It was still a live virus vaccine
so we were managing that way.
A lot of people, a lot of writing of permits.
And actually we actually beat it there by a day.
Everybody managed to get it done.
We were using the tiger team by then.
I was sending Von information and the rest of the team
where it got pretty well pushed out very nicely
and got taken care of.
So in the end as Ebola continued to move down its path,
we as a group of individuals trying to move it around
and follow all the regulations we've got,
managed to do it successfully.
It wasn't 100 percent.
I won't throw a stone at the various agencies,
well I won't say that.
The various areas that weren't able to figure out permitting
and things like that, because that turned
out to be the stopping point.
But part of it was the unwillingness
of some end users not to participate in a clinical trial.
So if you're not going to do that, you're not going
to be part of the IND, the FDA will stop you.
If you're not going to follow all the various rules,
and they are there for a reason and a purpose,
then it really does create an opportunity
for the system I feel to work properly where we said, "Nope,
then this won't happen this way," and that's what happened.
And so in the end the system, although it was challenged
on the timing frame, i.e. how fast things went through,
and the phone calls about turning around permits
and having them actually sufficient to help the people
on the borders that read it and did it,
let me tell you every time it hit a border
and somebody read Ebola on it, it stopped.
There were no questions, no ifs or buts.
It stopped.
And multiple people all stopped to look at it.
And quite honestly I guess that's what we want the system
to do because it could have been dangerous,
might have been dangerous, but that aspect worked.
So that's basically the end of my presentation
about how all this stuff can be made to operate.
We were pretty successful in that we actually ended
up getting all the materials
to the right places in the right time.
So I'm the closure on this, so I get to say we're getting ready
to do the question and answer session.
If you send your question answer in, I don't know who's managing
for this because I'm done.
Who's leading?