Drug Shortages: Why Are They a Recurrent Issue and What Can Regulatory Do to Prevent Them? - Chana Weinstock

February 22, 2024

Ruchika Talwar speaks with Chana Weinstock about the recent chemotherapy shortage affecting genitourinary cancers, notably muscle-invasive bladder cancer. Dr. Weinstock explains the complexity behind drug shortages, highlighting the manufacturing challenges of older, off-patent drugs like cisplatin and carboplatin. She discusses the FDA's limitations in mandating production increases and its strategies for mitigating shortages, including early notification from manufacturers and facilitating the entry of new generics. Drs. Talwar and Weinstock emphasize the role of advocacy, staying informed through professional guidelines, and the importance of communication in navigating and addressing drug shortages. They also touch on the broader issues of drug pricing and the need for systemic changes to prevent future shortages, underscoring the critical role of the GU oncology community in advocating for patient access to essential treatments.


Chana Weinstock, MD, Oncologist, U.S Food and Drug Administration, Baltimore, MD

Ruchika Talwar, MD, Urologic Oncology Fellow, Department of Urology, Vanderbilt University Medical Center, Nashville, TN

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Ruchika Talwar: Hi everyone, and welcome back to UroToday. My name is Ruchika Talwar, and we're here at GU ASCO 2024 in San Francisco. I'm joined today by Dr. Chana Weinstock, who's an oncologist and the genitourinary cancers lead at the FDA. Dr. Weinstock, thanks for being here with us today.

Chana Weinstock: Thank you so much for having me.

Ruchika Talwar: I'm really excited to feature a very important topic for our UroToday audience. In the past, we have spent a lot of time talking about the BCG shortage as it relates to non-muscle invasive bladder cancer. But this year we actually faced a new problem. We were faced with a platinum chemotherapy shortage, which affected a whole host of cancers, including, for urologists, our muscle-invasive bladder cancer population.

Neoadjuvant chemotherapy is a really important component of treating our muscle-invasive bladder cancer patients, and other platinum chemotherapy regimens are used for the metastatic bladder cancer population. So this was really affecting our entire GU oncology community, urologists and medical oncologists alike. Would you mind sharing a bit about this specific shortage?

Chana Weinstock: Yes, sure. So I'll just broaden this a little bit. Drug shortages are not a new problem. And unfortunately, they've been going on for a long time. The platinum shortage kind of brought this to the GU oncology world recently in the past year or so. But this is an ongoing issue. And unfortunately, it affects drugs that are older, that are off patent, and that are relatively difficult to make due to their nature. These are generally sterile injectable drugs for the most part. So cisplatin and carboplatin are examples of that, or their biologic products like BCG. So they're tricky to manufacture. And the downward pressure on pricing that exists because they're generic and they've been around for a while, that really comes into play here.

So what happened with cisplatin and carboplatin is that one of the manufacturers that was responsible for about 65% of the market share had manufacturing issues because, as I said, these are tricky to manufacture sterile injectables, to keep them safe, etc. So when this manufacturing issue occurred in November of 2022, it affected production and manufacturing of cisplatin. And there were only five manufacturers of cisplatin in the US. What happened was that that affected the supply of cisplatin to the market, and it really became an issue in certain centers.

Larger centers that heard of the shortage were able to, so to say, stockpile cisplatin supply early on, but smaller centers and some other centers really struggled. And that led to a downstream effect on carboplatin supply because a lot of carboplatin was being used in place of cisplatin. So there was sort of this ripple effect there. And that explains the shortage.

Ruchika Talwar: Yeah. I think you highlight a couple of important points. It's really easy for patient-facing clinicians to often say, "Well, listen, there's an impending shortage. We should be able to anticipate this. Why not just ramp up supply?" And it really doesn't work that way. There's not a lot of built-in cushion here, as we've seen with BCG, for example. Same thing. There's a very limited number of places where the drug is made, and there's a lot of pressure on the system.

And I think a lot of folks say, "Well, okay, FDA, we're looking to you. Let's have you solve this problem." And you and I have discussed this before. I had the opportunity to do some work in DC over the summer in a congressional office. And I too was one of those people who reached out to our FDA liaison once we started getting constituent letters coming in complaining about the fact that cancer patients were unable to undergo treatment in certain areas in community centers. Community oncologists really faced this, and in some rural areas.

And tell me a little bit about the FDA's constraints here. How does the FDA as an agency work? Why were they not able to kind of jump in right away and tell the manufacturer, "Hey, start opening up new plants," or whatnot?

Chana Weinstock: First of all, I want to really thank you for your advocacy work. I think advocacy work is incredibly important. And I also want to highlight the fact that you mentioned patients were facing the shortage situation. It's just so unfortunate that a patient with bladder cancer has to think about this consideration in addition to their cancer diagnosis. So really, as much as we can do to help alleviate these shortages, the more we can do, the better.

So, in terms of what the FDA can and cannot do. So the FDA cannot require a company to start manufacturing a drug, and we can't require a drug to ramp up manufacturing or manufacture more of a drug. That's not within our purview. What we can do, and what's actually very helpful in many situations and really can prevent a lot of drug shortages, is require early notification of drug shortages by manufacturers. And that's actually through legislation that was passed in 2012. It's called FDASIA. And that requires manufacturers to inform us of impending supply issues and manufacturing disruptions.

So that's actually very helpful if we work together with manufacturers when there's a shortage situation. And this came into play working together with manufacturers of platinum agents really did help turn the shortage around to a large extent. We worked with a manufacturer to bring a new generic for carboplatin onto the market, and then there was some new revised manufacturing of old cisplatin and carboplatin drugs that were off the market where we worked carefully with the manufacturer to bring them back on the market. And we also allowed for the importation of cisplatin from another country when we determined that it was safe to do so. So there was a lot of effort on our part to really try to bring cisplatin and carboplatin back onto the market in a safe way.

And I also want to highlight that there are changing standards of care in bladder cancer. So with new approvals, the demand for platinum agents may be going down as well. So that's something else that the FDA has done, not related to the shortage, but that may actually change the demand for platinum in bladder cancer, and hopefully, that'll be helpful as well.

Ruchika Talwar: Yeah, it's a very complex space. The FDA plays a certain role, but even if certain flexibilities allow for substitutions or perhaps using drugs that are newly approved, I think a lot of patients still face hurdles because the insurance company has to pay for the drug. There needs to be an approval on that side too, and the center needs to be able to stock the drug and obtain it and administer it. So lots of moving parts here.

And that is why, going back to your point about advocacy, our advocacy is so important even outside of the space of just writing to our congressional representatives and having them perhaps support legislation that can help arm the FDA with the tools they need to respond to these situations. We can certainly advocate from an organized medicine perspective to insurance companies to ensure that burdens and prior authorizations are not in place in times of such shortages and allow for flexibilities regarding things like, for example, step therapy. There are certain agents that can't be used until other, sometimes cheaper, sometimes easier to obtain agents have been failed.

So, to our audience, just a couple of things to keep in mind and why the GU clinician voice is so important here. Tell me a bit about what we can do outside of perhaps just advocacy, whether it's communicating with our patients, communicating with our centers, if another shortage ever arises because, as you alluded to, it's not outside of the realm of possibility. Shortages are definitely an ongoing issue in all of medicine.

Chana Weinstock: Yeah, it's a great question. And again, I think it's a problem that's not going away, unfortunately, anytime soon. There are issues outside of the scope of what the FDA can do, what an individual clinician can do, really related to the pricing structures of these older generic drugs. And I think that really needs to change, and that's no one person or one organization is going to do that.

But really, many professional societies have come out with guidelines that have really addressed questions that have arisen in the shortage situation. And keeping up to date with those practice guidelines in shortage situations is very important. Communicating, finding out where supply is more readily available, and where to direct patients. I think communication and keeping up with society guidelines are very important pieces for clinicians. And I know I keep mentioning advocacy, but I think that's where legislative change is going to come from.

Ruchika Talwar: Yeah, there were some provisions that were included originally in the summer in the PAHPA reauthorization bills. The PAHPA was the Pandemic Authorization and Hazards Prevention bill that was up for essentially renewal. And unfortunately, a lot of those did not make it into the bill. Again, just sort of framing this for the audience, some of those legislative directives included things like continuing flexibilities about importing drugs, ensuring that there are periodic checks in place with manufacturers specifically centered around drugs that have the issues that you've already discussed, drugs that perhaps can't be manufactured in a flexible manner, specific pricing constraints, etc.

So although that wasn't included in the reauthorization, I am really optimistic because it's an issue that is now at the forefront of health policy. We're talking about it. Whether it's chemotherapy, sterile saline injectables, there were a variety of drugs that, both because of stress from the pandemic but also some of the issues we've already discussed, were facing shortages. So I'm optimistic. We'll see. We'll see. But I think that you've shared an incredible amount of wisdom with our audience here. And I just wanted to ask you for any final words.

Chana Weinstock: So thank you for that. I think our drug shortage supply staff, I really want to highlight the work they do because through early notification, through working with manufacturers, through thinking creatively, they prevent hundreds of drug shortages per year. And the actual number of drug shortages that have occurred, and again, we don't want there to be any ultimately, but that's remained flat over the past 10 years or so since FDASIA was passed. So I do want to highlight that there is a lot of effort by my colleagues at the FDA related to drug shortages. And I think it's working to some extent. There's definitely more that can be done.

And I also want to say that we as an office, we're involved in the regulation of new drugs, but some of the issues come into play with trial designs, specifically with the BCG shortage. How do you incorporate patients with non-muscle invasive bladder cancer who haven't received what we would've called adequate doses of BCG due to the shortage and how to incorporate those patients onto subsequent clinical trials? So these are things that we've been thinking about very long and hard. We've had open public workshops about this topic. So I think there are a lot of people working on this, a lot of my colleagues. And there's been hopefully a lot of success so far with a ways to go as well.

Ruchika Talwar: Thank you. Thank you for being here with us today. And to our UroToday audience, thanks as always for joining us. We'll see you next time.