Understanding the Complex Landscape of Oncology Drug Shortages

Nathan Bahary, MD, PhD

The increase of oncology drug shortages in the United States has become a significant concern that has affected many healthcare institutions across the nation. According to Nathan Bahary, MD, PhD, while these shortages are not new, more is needed from congress and legislation to be proactive rather than reactive moving forward.

“We have to ask our representatives, we have to ask our FDA, can we trust that you're going to try to be forward thinking and how can you help us see that these are coming? Because that helps us to be able to plan for it so we can make these decisions ahead of time, and maybe, how can we avoid it? Let's create a policy that we can be proactive about,” said Bahary, division chief of medical oncology and director of clinical cancer research at the Allegheny Health Network Cancer Institute in an interview with Targeted Oncology^TM.

There are several factors that contribute to oncology drug shortages, including the outsourcing of drug manufacturing to overseas facilities, limited manufacturing sources, and the increased demand of agents across the world. Additionally, disruptions in manufacturing or supply chains and regulatory issues may lead to delays and shortages of these necessary treatments for patients with cancer.

To further address these challenges, a collaborative effort between pharmaceutical companies, regulatory agencies, healthcare providers, and policymakers is needed to combat shortages in the future.

In the interview, Bahary explains what factors have contributed to the rise in oncology drug shortages, and emphasizes the importance of proactive measures moving forward, while also suggesting the importance of policy changes and increased communication.

Targeted Oncology: What has led to the increase in oncology drug shortages?

Bahary: First, there have been drug shortages going on for years, this is not the first time we’ve had drug shortages. It’s become a little bit more acute in the oncology world as a number of manufacturers, for generic drugs, such as cisplatin, have gone overseas. And what’s happened then is that they don’t have the same oversight from the FDA. For cisplatin, we found out in India, there were production problems. But by this point that we found out there's production problems and the FDA halts the shipments, we're well into what's going to become a shortage.

I think a lot of this has to do with the fact that most American pharmaceutical companies are focusing on newer drugs and generics, and many of them are going overseas. There can be problems with distribution, during COVID it was clearly a problem, and that's only being worked out now. But then there's also issues with ensuring the potency and the equivalents of these drugs coming in from overseas when the FDA doesn't necessarily have oversight of them. We've also done this to make some money where people are doing it as a single manufacturer for a number of these drugs. If that line goes down, there's a problem.

With cisplatin, which we alluded to when there was a shortage, the FDA helped us dramatically by allowing imports via Canada from China. I can speak to the Allegheny Health Network. Our Cancer Institute, at the moment, is doing well with cisplatin. We've managed to get enough from Canada to alleviate the shortages, but it's really distributor by distributor, so [we’ve] got to be careful. That's not necessarily true across the country, and we could have a shortage in the future that somebody else doesn't have a shortage of.

One of the things that I'd love to be able to see happen is some sort of push through Congress, through legislation, if necessary, to try to bring some of that back into the country, whether that's a tax abatement as special tax district, some sort of subsidy, so that it's worthwhile for us to manufacture as well. Now, it may not be to the quantity that's coming from overseas, but something that we know that can't be interrupted and that the FDA has oversight of. It takes time to create a facility or so. I'd like to see some effort on our part to see that these things are coming and try to intercede with them ahead of time.

How has AHN been impacted by these shortages?

We've been very lucky at the Allegheny Health Network Cancer Institute. Our pharmacy has been on top of this, and they foresaw the shortages, which helps in a couple of ways. Not far beyond everybody, but they began to play for it. One thing you can do is, we are a network of a number of hospitals and every hospital has some storage of it. They've been able to move supplies from 1 hospital to another within the network to support us, which may not be possible if you're a small hospital in the middle of Idaho.

We were also able to begin to look ahead of time and say, for cisplatin, when there was somewhat of a shortage, we never ran out. There was never anybody who had a curative intent protocol here that we didn't get them cisplatin. It did require us to make some decisions if it's not curative, and that there's an equivalent. Even if people are used to using cisplatin, can we use another drug instead?

We worked with the oncologist to do that and to preserve this supply, and we made it through that bottleneck. What happens 3 months from now is unclear. I'm going to have to look at our pharmacy and our pharmacist staff to kind of be on top of this and try to help us. But I think it's important for people to realize how to empower themselves to ask questions about their own chemotherapy. Is there a shortage? How are you addressing it? That kind of thing and realize are, and that in most cases, we can find alternatives for them. We take it seriously. I hope we can begin addressing it as a medical profession.

Since the United States is currently importing agents from China, can you discuss your thoughts on administering products that aren't FDA approved?

The question is why they're not. Right now, China and the US are at odds. Many of these manufacturers have ensured the purity and have had people look at them at independent labs. We know that they're pure, we think they're efficacious, and the FDA, maybe because of politics or other reasons, hasn't approved it, because we're trying to keep our own pipelines. But look, we need the drug from wherever it comes. So, do I have to halt? Yes. Do we think about it twice? Yes. I've got to trust that the FDA has done their basic research and knows that we're not in risk of harming anybody. I certainly don't have the expertise to do that as that takes a regulatory agency and the oversight, and so it causes me to pause. But I do have faith in our oversight in our medical system to say that it's equivalent, and it's okay.

In the face of these shortages, what are alternate treatments experts have turned to?

For some, when we had less cisplatin, but we had some carboplatin, [we could] substitute 1 for the other. There are certain ones that you don't want in ovarian cancer, certain breast cancers, so carboplatin is the agent we want to use, and we're going to preserve it for that. But sometimes you could use carboplatin instead of cisplatin. There are other things where instead of cisplatin, we could use a different drugs such as in bile duct tumors, cholangiocarcinomas, and there's pretty good data in the first-line that [paclitaxel] can be substituted for metastatic disease where it's not of curative intent. There’s reasonable data for that, but every disease has its own limitations.

My thing is that when an oncologist is going to see a patient and say, we're going to substitute this because of a shortage, [patients should] absolutely ask, what's the data? How good is the data? We've never had to turn somebody down, and give the [inferior] drug, but as I've told people before, my fear is, when are these things decided if there's a limit of a drug or who is more worthy of that drug? The young person who's got a testicular tumor, a middle-aged person who's got a bile duct tumor, or an older person with lung cancer? That's the thing where I'd have trouble sleeping. I would rather make those decisions before we're in the situation, when we can plan, and see what the viable alternatives are, and be honest with our patients for the data. There is a reasonable amount of data on what we can do for some of these drugs.

How do you foresee these shortages impacting cancer research or affecting clinical trials moving forward?

That's a little bit more difficult because a lot of clinical trials mandate a certain drug. For instance, there was a drug in cholangiocarcinoma that was being used, [paclitaxel], and they were looking at it with cisplatin and gemcitabine because for a while, a couple years ago, there was a [paclitaxel] shortage. We could just not enroll people on the trial, because [they] had to have that drug. Clinical trials are very different. If a clinical trial says, in order to get on it, they have to have a disease in a certain state, and they can't have any of these issues, and you have to have a certain amount of not too much disease or whatever is mandated there, we can't change that if we want to have data that's helpful. We don't want to get at the end when say 3 people got treated with that, and 5 with this. How do you compare it? I think that these drug shortages have impacted certain trials and accrual. Hopefully, they're short lived. Because many of these trials are nationwide at large, even if we lost a couple of months, we were able to fulfill the accrual goals, and be able to understand what's going on. We want to make our information and the results as valid as possible.

Also, we want to make availability of some of these places. Why only is it at major institutions that this trial will be available? They can impact that way. We've had a couple of times where in past years, people have come to us or we've had to send somebody else for a trial that's opening multiple places, if there's a shortage of something, but it's not that common. Just know that everybody's working to try to keep this going, but it requires communication. We have to be open and have to be honest with the patients. For our cooperative groups, and these different institutions coming together to run trials, they have to be honest with each other about what's going on, and then we can best serve the patients.

How do you think the long-term effects might impact us in the future and how do you think we can kind of learn from challenges in the past?

I think it is vital that if people are going to say to their representatives, to Congress, to whomever it is that we got write letters to the FDA saying we've had these drug shortages, and remember, they've been drug shortages of antibiotics that have to be your will have to substitute for them that we've had to do. And so far, they're equivalent, but we don't know that there will always be the case and say, what are the basic problems? One was that there was overseas manufacturing, so let's be proactive instead of being reactive, saying we're going to have a shortage of this antibiotic 2 months from now because something happened in Pfizer, getting hit by a tornado. I don't know that, but let's say there was. Instead of being reactive to it, start thinking about, what if there's a problem at a single plant? How do we ensure there's a backup of it? How do we ensure if there's a problem overseas? Let's be honest, there's a problem here in our area too. How do we see it? We have to ask our representatives, we have to ask our FDA, and say, can we trust that you're going to try to be forward thinking and how can you help us see that these are coming? Because that helps us to be able to plan for it so we can make these decisions ahead of time, and maybe, how can we avoid it? Let's create a policy that we can be proactive about.

What advice would you have for community oncologists?

I would tell the community oncologists that they should be talking to the distributors and staff for their drugs, if they're doing it themselves. Many people are offering it centrally, and if there's a problem in your area, to look at a larger system to see if they can help you. Now, we may not be able to ship a drug, but we can certainly help by treating your patient for a period of time. It may not be convenient, but they can also reach out to us. I've had patients reach out to me for my expertise in GI cancers. I've had people ask me, who can I reach out to for ovarian cancers, or breast cancer, or GU cancers, kidneys, bladders, and testicular? What might we substitute for? If they're not 100% certain of the data, we're always willing to help them.

It is important for communication from the patients to the oncologist too. Patients should not run scared. They should be concerned, rightfully so, but they should [ask if there] is a problem that you foresee, yes or no. If there are, how are you going to do it? What's the data? Why do you want to treat me with that? Why do you want to substitute something for me? [They are] perfectly logical questions.