Soumi Saha, PharmD, JD, Discusses COVID-19–Related Drug Shortages and Policy Solutions

Soumi Saha, PharmD, JD, senior director of advocacy, Premier, Inc

00:00

Center for Biosimilars (CfB): I'm Mary Caffrey, here on behalf of the Center for Biosimilars®. We're here to welcome Dr Soumi Saha, senior director of advocacy at Premier. Welcome.

00:09

Saha: Thank you for having me, Mary.

00:10

CfB: So, we're here to discuss a new survey that has uncovered drug shortages that have been brought on by [coronavirus disease] COVID-19. And from your survey that was released last week it appears that with each passing day, we're seeing more and more shortages of the drugs that are designed to care for the COVID-19 patients. Can you talk to us about the major findings?

00:29

Saha: Yeah, absolutely. So, Premier conducted this study from March 20th to 26th. It went to our over 4000 hospitals that Premier works with and 175,000 non-acute providers. From a response perspective, we had about 337 unique hospitals and health systems that responded as well as 100 non-acute sites that represented nursing homes, long-term care pharmacies, as well as home infusion pharmacies.

A couple key findings here: First, we did find that the acute settings are seeming to be having a harder time with drug shortages than the non-acute settings. That makes sense given the influx of patients that the acute settings are currently seeing. So, therefore, our recommendation would be that the immediate focus should be on ensuring acute settings have access to these drugs, but also realizing that non-acute settings are likely not far behind. The survey also focused on several classes of drugs that are specific for treating patients with COVID-19 and found throughout that regardless of where an entity was located, individuals are indicating shortages of antivirals and malarial drugs that are used to intubate patients, such as neuromuscular blockers, sedatives, and anesthetics. We've also seen shortages of IV fluids, antibiotics, as well as some typical fever and pain medications as simple as Tylenol or ibuprofen. What we also saw—not only is the demand for these drugs increasing, so folks are ordering more of them—but what we're also seeing is the fill rate is decreasing.

The fill rate refers to what you order versus what you receive in an order. And why we focus on that is any reduction in a fill rate below 100% typically indicates an early warning signal of a potential shortage or an oncoming shortage. So that's why it's so important to focus on those fill rates. That really tells us a lot.

CfB: The figures that jumped out, of course, are the drugs that President Trump has discussed during the press briefings, particularly hydroxychloroquine. How much of the attention to this drug is warranted and how much of it is, maybe speculative? We've heard a lot about potential for hoarding, for people getting access to the drug that maybe shouldn't have access to it. Can you tell us a little bit about those, those things that are developing?

Saha: Yeah, so great questions. And one of the challenges with COVID-19 is there are no known therapeutic cures or true therapies that we know definitively work. And one of the challenges is that anytime we see a study come out, regardless of the size of the patient population that it encompasses, if it has positive outcomes, we're immediately seeing a run on those drugs. And so, what's unclear right now is, “Is it hoarding, or is it appropriate stocking?” That's not clear yet. So, for hydroxychloroquine and chloroquine within 24 hours, we saw traditional supply chain channels absolutely depleted. And unfortunately, I think that's going to continue, as new therapies have positive outcomes from foreign sources.

It's clear and critical moving forward that an entity like CDC, for example, play a role where they help vet any of these studies that are coming from international sources and help determine their merit, so that we don't see this occurring in the future. And I can give you another example. There was a recent study in the past 96 hours that looked at ascorbic acid, and determined in a small patient population that ascorbic acid helped patients on ventilators get off that ventilator sooner rather than later. And that immediately overnight, you saw an increase in ordering for ascorbic acid and depletion on the supply chain channels.

CfB: So, it's ascorbic acid. That's vitamin C, basically, correct?

04:25

Saha: That is

04:26

CfB: Yeah, okay. So, that's like a common drug. That's not something we would think about having a shortage of.

04:32

Saha: Except, this used to be a DESI drug [Drug Efficacy Study Implementation]. So, in the past few years, a new manufacturer came to market. It is a branded product now, sole manufacturer in the United States, and there are no generic alternatives available. So, the ability of that single manufacturer to ramp up production is limited. While it's a very common drug, and you think about it, as you know what you have in your orange juice, for example, from a drug perspective, it's not quite as simple because of the challenges with active inclusivity and other things.

05:01

CfB: Wow. So, your survey found that the most acute shortages are, not surprisingly, are happening in the New York area! That makes sense. But could shortages quickly become a big problem in other parts of the country? And where might that happen?

05:14

Saha: Absolutely. So, one thing that our study did was [it] looked at geographical areas when we focused on the 3 major hotspots that are known today: Washington State, California, and New York. And what we found was, as you mentioned, in New York, the shortage just seemed to be more imminent or drastic than what we're seeing based upon the national average. Now, what was interesting is that, when you look at Washington, shortages were not as high as in New York. And then shortages in California were technically higher than in New York. So, this got us thinking. Since Washington was the first major hotspot, are they not seeing the same level of shortages because they had full access to all available resources at that time? And are things in California worse than New York because New York is currently pulling resources away? From what otherwise would be available in California, or it could be due to regional distribution challenges as well. So, one of the big concerns that this survey seems to start illuminating is that what will happen for future hotspots? As disease progresses in areas like Chicago or New Orleans, for example, if New York is continuing to pull available resources, what is left for these additional hotspots that come online? And that's one of the big concerns moving forward.

06:29

CfB: Well, a big takeaway from this survey is that these are not short-term problems. These are problems that are presenting themselves now, but are really long in the making. What are the top long- term issues that need to be addressed so that we don't find ourselves in this position ever again?

06:46

Saha: Great. So, one [issue] is there's no single cause for shortages and so there can't be a single solution for shortages. In this particular case, most of the shortages we are seeing are due to just a sheer increase in volume and demand, not because of manufacturing issues or quality issues which we may otherwise see, but a few different things here. So, almost all of these drugs are produced internationally, or they're active pharmaceutical ingredients, which is the main component of these drugs is manufactured globally.

One thing that the [United States] could do is look at how do you incentivize onshore manufacturing of drugs that are considered critical moving forward? How do you identify capacity within the United States? How we can bring some of this manufacturing back domestically, immediately, and do so in conjunction with the FDA—because we would need a streamlined and very efficient FDA approval process. Normally, it takes months to years to have an abbreviated new drug application approved, but we don't have the luxury of time here. So, it would definitely have to be done in concert with the FDA.

07:53

CfB: So, you've made a lot of recommendations on how what we should do next. There are regulatory solutions that you've talked about—and there are also financial incentives. I would say that those are kind of the 2 buckets that the solutions that you outlined fall into. What's more important that we do first, the regulatory solutions or those financial incentives? Where should we start?

08:14

Saha: Thinking the short term, we need to start with the regulatory incentives, and work through streamlining and creating efficiencies in the process. So, we can begin onshore domestic manufacturing pretty immediately. The challenge is going to be long term, is going to be creating those financial incentives. Now, there was a provision that passed as part of the CARES Act that requires the National Academies of Medicine to study the foreign reliance on manufacturing for drugs and develop recommendations for how you incentivize financially or create those market based incentives for onshore manufacturing. So that's going to be a little bit more long term. But the short term is how do you work through that regulatory approval process to identify existing capacity that's already within—in the United States—and leverage that to create and manufacture the drugs that are of greatest need right now.

09:06

CfB: One of the solutions you talk about is sharing among hospitals. And you know, just as [New York] Governor [Andrew] Cuomo has been talking about sharing—sharing the ventilators—maybe we should be sharing the supply and moving the supply around, but there's barriers to that. Can you talk about how that might work in the real world?

09:20

Saha: Yeah, so there are several barriers to that. Typically, any hospital or any registered licensed pharmacy is limited to only being able to share a maximum of 5% of their inventory with another pharmacy without registering as a wholesale distributor, typically referred to as the 5% rule in pharmacy. So, one thing that we've asked is for the federal government to temporarily waive that 5% distribution rule. Many states would also have to provide a similar waiver because they have state based laws that mimic that. But that would at least allow us to move drugs from an area that doesn't have as great of a need to areas of greater need. So, if we find that there's a lot of hydroxychloroquine in South Dakota, for example, how quickly can they shift that product to entities in New Orleans, for example, as they come up and ramp up in need. And clearing that 5% distribution rule would allow hospital-to-hospital direct transfer versus having to go back through the wholesale distribution channel, which may cause delay….

10:23

CfB: And probably add to cost as well, I would imagine.

10:25

Saha: Absolutely.

10:26

CfB: Okay. So, in the current crisis, some of the problems seem to stem from the fact that China has become such a big player in drug production, and Wuhan, which was the where it all began, in particular, has become a big focus not only in, in drug manufacturing, but also in the world of biosimilars. Right before all this happened, there had been an announcement for [Celltrion] to start construction on a major biosimilar plant. Should the United States take a bigger role in manufacturing its own drugs and we start to bring more than manufacturing back here?

10:59

Saha: Yeah. That's one thing that Premier’s been speaking about for a while. We were huge proponents of the mitigating emergency drug shortages act components of which were included in pairs in sections 3111 and 3112. And so that's where that National Academies of Medicine report comes into play that would require the US government to look at that foreign reliance on manufacturing and look at how we incentivize domestic manufacturing of not only the finished product but also the active pharmaceutical ingredients as well. And we would like to see that for solid dosage forms sterile injectables as well as biosimilars.

11:34

CfB: Okay. You mentioned some steps Congress has already taken. It’s expected that we're going to have more legislation pretty soon. What's the next thing Congress should put in the next bill that would help alleviate some of these problems?

11:47

Saha: Yeah, so to your point about financial incentives Currently, the way it's written, those are a little bit more long term. But some of the things that we're thinking about are can we do some sort of tax benefits or tax cuts for pharmaceutical companies that are willing to step up to the plate, and help increase production of these critical drugs, potentially invoking the Defense Production Act [DPA] to include drugs as well, because that has not been done thus far, the DPA thus far has been limited to ventilators and personal protective equipment. And so that's kind of what we're thinking right now: How do we incentivize manufacturers to do that in the current state?

12:30

CfB: Are there any success stories out there of drug sharing or drug transfer or production issues, any anything that's been done well, that's innovative that we should be doing more of?

12:39

Saha: Well, one thing I would like to applaud is several of the drugs that are used to sedate patients in order to intubate them are controlled substances, fentanyl, for example, and fentanyl has been on the drug shortage list for quite some time. But in order to increase production of fentanyl, you also need to work collectively with the DEA in order to really additional product or quota to able manufacturers. And just last week, DEA did increase available quota to both manufacturers and 503. b outsourcing facilities for fentanyl. So, I do believe that that's a great success story that should hopefully help alleviate some of those shortages for fentanyl that we're seeing.

13:19

CfB: Okay. And is there a drug shortage on the horizon that no one's paying attention to that we should be paying attention to?

13:26

Saha: That's hard to tell. Because, again, anytime you're going to see any positive outcomes associated with any study from any source, you're going to see an immediate drug shortage of that product. I mentioned ascorbic acid earlier, but the reality is, is that we don't know what's next because we don't know what's going to come down the pike. And then we'll also have to be a little concerned about ancillary shortages as well. So, countries like India have export bans in place for 14 drugs and their corresponding API. Are we going to see additional countries put similar export bans in place that prevent the United States from obtaining those products? And then as the disease progresses globally, manufacturing shutdowns in several of these countries could potentially impact the drug supply chain as well. So right now, it's a little too soon to pinpoint exactly what the next shortages [will be], but the bottom line is, there will be more shortages, unfortunately.

14:25

CfB: Well, thanks for joining us—and thanks for joining the Center for Biosimilars^®.

Saha: Of course. Thank you