We're actually gonna dive straight in with our main story this week, which concerns medication.

It's the subject of this 1980s PSA where a group of pills try and discourage kids from eating them.

This is serious. Serious.

We could make you delirious. Delirious.

You should have a healthy fear of us. Fear of us.

Too much of us is dangerous.

No, no, no. We're not candy. Believe us.

Even though we look so fine and dandy.

When you're sick, we come in handy.

But we're not candy. No, no.

Listen, I do appreciate the message there, but unfortunately, I don't think I've ever wanted to eat a pile of loose pills more.

I mean, there are literally candy commercials that have made me want to eat their product less than those adorable singing Skittles.

Get into my mouth.

Specifically, we're gonna focus on generic medications.

You know, drugs that contain the same active ingredients, dosage form, strength, safety, quality, and intended use as their brand name counterparts, or as this director of pharmacy services puts it...

The generic is the same as the brand.

There's no difference.

The only difference might be in the filler, not the active ingredient.

It's that active ingredient that's the same.

That's the important part.

Uh, that, well, that's the part that does the magic, yes.

Now, I'll be honest, the part that does the magic is a weird enough phrase as is

before you realize they chose to use Viagra as the example there.

Forcing all of us to remember that in certain cases, doing the magic could well mean making Grandpa rock hard.

But generics are, by far, the most common type of medication people take in the US.

They currently make up more than 90% of all US prescriptions.

You may even take them without realizing it.

You may have been prescribed Zoloft, but if you look at your bottle, it might say Sertraline.

That's the generic.

Similarly, if you're prescribed Lexapro, your bottle might say Escitalopram.

Or if you're prescribed Prozac, it might say Fluoxetine.

And if you've never taken any of those meds, then congratulations on being a happy, well-adjusted person.

And kindly, go fuck yourself.

But unfortunately, in recent years, there have been eye-catching stories about sudden drug shortages, often involving some exceptionally common generics.

Mass General has a tough enough job without having to deal with a drug shortage.

Thank you.

I never thought we would get to a point in the US healthcare system

where we wouldn't have essential medicines to be able to treat patients.

The hospital can't get enough of the blood thinner Heparin, crucial for cardiac surgery.

How surprising was it for you to hear that there was a Heparin shortage?

Oh, it was completely surprising.

It's extremely frustrating.

I mean, it, it's like McDonald's running out of ketchup.

Yeah, that's a pretty apt comparison.

A hospital without Heparin is indeed like a McDonald's without ketchup

or a Subway without bread or a Chick-fil-A without the pervading undercurrent of homophobia.

We've come to expect certain things at certain places.

And it's not just Heparin.

Apparently, there are 227 active drug shortages right now, and that's including many essential medicines,

with some of the worst shortages involving sterile injectables, drugs often used in IV bags

that are a staple of hospital treatment.

It's now at the point that the AMA has deemed drug shortages to be an urgent public health crisis

and a national security threat.

And for anyone relying on a certain drug, suddenly learning of a shortage can be terrifying.

Take this woman, whose chemotherapy was delayed for exactly that reason.

It's very frustrating to know that there's a standard of care,

uh, these two generic drugs, and I can't get them.

Someday I'm gonna die.

I really would rather not

die because the standard generic drugs weren't available to me, and I, I can't imagine my family having that doubt.

Was it the cancer, or was it that there was not enough chemotherapy and it got rationed?

Right. That is a question no family should have to ask after a loved one's passing.

It's right up there with, "Why did Dad store all these old maps of the San Francisco Bay Area in the attic?"

And, "Why did he hide this dog-eared guidebook on how to make cipher messages?"

And, "Why did he put this old pair of thick-rimmed glasses, a handgun, and a knife in this shoebox with a, marked with zodiac symbol? Oh, fu-u-u-uck."

And as you are about to see, sudden shortages are just the beginning of the issues here.

So given that, tonight, let's talk about generic drugs, how they're made, where they're made, and what the problems can be.

And let's start with the basics.

Under current law, if a company invents and patents a drug, it's allowed the exclusive right to sell it for a certain number of years.

The idea being, it can then recoup its cost on research and development, as well as, you know, make a shit ton in profit.

But once that patent expires, generic manufacturers can make their own version and usually charge far less.

Take, as it seems to be the go-to example here, Viagra.

Pfizer introduced Viagra onto the market in 1998, and had patent protections for nearly two decades.

Then, cheaper generic versions, like all these, started to emerge, which was frankly great news for thrifty, horny grandpas everywhere.

Similarly, while Ozempic's expensive right now, cheaper generics will presumably come when its patents expire.

And from a consumer cost perspective, generics have been great, collectively saving patients of the healthcare system trillions of dollars, and often slashing prices by as much as 85%.

And that is mainly because the major buyers that purchase drugs on behalf of hospitals and pharmacy chains are strongly incentivized to seek out the lowest cost product.

The problem is, as prices get driven down, companies can suddenly decide that making a generic is no longer profitable enough for them, which can result in worryingly few manufacturers making certain drugs or in extreme cases, only one doing it.

And that can be a big issue.

Take this story from 2019.

Vincristine is one of the IV drugs used in chemotherapy to treat about 85% of pediatric cancer cases.

But this summer, Teva, one of two US companies that makes it, announced they would stop making it, citing a business move.

Only now is it starting to catch up to patients.

Brenna's mom, Kristi, fears the worst.

Relapse, or, or in her case, not ever beating the cancer.

The kids who don't finish their treatment won't get a cure.

I'm completely disheartened that a business decision stands to kill 15,000 kids a year

Christy hopes with the help of celebrities like Kevin Bacon, who has also spoken about the drug shortage,

she'll finally start to make some waves of change for the sake of her daughter.

Look, that is terrible and it is clearly absurd that it's somehow up to Kevin Bacon-

To try and fix this, though, and I hate to be a petty bitch,

technically he didn't post about that shortage.

His wife, Kyra Sedgwick, did.

Kevin Bacon just retweeted it, which is just not the same.

Still, I'm glad that he did it, mainly to get the word out,

but also because it was a refreshing break from the unhinged content that filled up his feed,

like this photo of him showing off a giant zucchini.

And this video where he made a necklace out of popcorn

so that, and this is true, a goat could snack on it-

While he serenaded it with a Harry Styles song.

The man's entire Twitter feed was an LSD fever dream.

The point is, while I am glad that Kevin Bacon, but mostly Kyra Sedgwick- Helped get the word out and that woman's daughter was eventually able to get the drug she needed, we should not have to rely on celebrities to ensure adequate supplies of drugs to treat kids with cancer.

But the broader story there is not uncommon.

Basically, there were two companies left making the drug.

One left the market, and when the other had a production glitch, suddenly there was a big problem.

And the thing is, glitches can happen in production.

That's true in drug manufacturing generally, but even more so in the generic space where companies are in a race to make drugs at the cheapest possible cost.

And things have gotten worse as production's increasingly moved overseas to chase even more savings.

In fact, these days, roughly 60% of prescription tablets and capsules for the US market are made in India, and it's estimated nearly a quarter of our generic drug supply contains active ingredients originated from China.

And look, I am not saying manufacturing drugs in other countries is inherently bad, but being that reliant on them can be a problem.

It's like finding out 80% of America's milk supply comes from cows personally milked by Javier Bardem.

Nothing against the man personally.

I love the guy.

But if anything happens to that beautiful Spaniard, our breakfasts going forward are going to be fucked.

And there's growing evidence that where generics are manufactured can make a difference.

A study last year found the risk of serious adverse events was 54% higher with generics made in India compared with those made here in the US.

And researchers who've tested them have found that they can vary wildly in quality, with issues ranging from contamination to the wrong dosage to problems with how the medication dissolves.

Just listen to this woman who had a heart transplant and was reliant on a drug called tacrolimus to stop her body rejecting it.

She found that some generic versions of that drug made by overseas companies didn't work as well, and that could have had massive consequences.

If you get a one-month supply of an anti-rejection medication that isn't made right, what's the consequence for you?

Death.

I would die.

To prevent her body from rejecting her new heart, her medication levels are supposed to be between 6.8 and 7.5.

On one brand of generic tacrolimus, she tested at 3.9.

I was open for that whole week for rejection.

I'm like, "Oh my God."

She switched to another, which elevated her blood levels to 9.9, an overdose,

leaving her newly transplanted heart vulnerable to life-threatening complications.

I started shaking again, which is the side effect of being overdosed on tacrolimus.

You shake.

It is a complete crapshoot which one you're gonna get when your pharmacy picks one to give you.

That's frightening. Yeah, of course it is.

You don't want your life-saving medicine to have the same selling point as an LOL Surprise ball.

Because it could be anything in there.

It could be Kitty Queen or Coconut Cutie or Steve Buscemi.

And while obviously some very specific little weird girl will love that,

when it comes to your medicine bottle, you want a high degree of certainty regarding what's inside.

But unfortunately, too often that is just not the case.

In fact, when the DOD had an independent lab test the military's most critical drugs,

out of the first group that they looked at,

15% of suppliers scored red, meaning their product had major quality concerns.

And when it came to tacrolimus, the medication that woman was taking to stop her body hitting eject on her new heart-

One third of samples tested red, which is not good.

And the harms of poorly made drugs aren't just theoretical.

People have been hurt.

Take what happened a few years back with something as simple as generic over-the-counter eye drops.

She said, "You have an ulcer on your eye, and if we don't get this under control, you will lose all your vision."

In 2023, four people died. Four had to have their eyes removed,

14 lost vision, and 114 suffered infections from contaminated eye drops made in India.

Holy shit.

Any time you hear about someone getting their eyes removed- And that someone is not Mr. Potato Head- It is automatically horrifying.

And at this point, you might be thinking, "Where the fuck is the FDA in all this?

Aren't they supposed to be making sure that no one has to get their eyeballs removed?"

Well, they are indeed tasked with reviewing generic drugs and inspecting factories to make sure everything's safe, but unfortunately, the agency isn't resourced or staffed remotely well enough to inspect factories regularly, especially given so many are now halfway around the world.

And what that means in practice is years can pass between inspections.

And even when the FDA does show up to a factory overseas, some companies have tried to obscure any problems.

Just take what happened at a factory in India run by a company called Intas.

FDA inspectors found a cascade of failure, including a worker throwing acid into a trash bin to destroy test records.

Wow, that looks bad because let me be clear here, there's plenty of good uses for acid.

You can use it to neutralize excess alkalinity in a chemical solution, or to increase hydrogen ion concentration, or to melt all of Manchester City's Premier League title medals.

But- ... destroying critical drug test results is not one of them.

And on top of that, you should know while surprise FDA inspections are common for US factories, most FDA inspections done overseas are actually announced beforehand, allowing manufacturers to both prepare for them and potentially hide any issues.

In fact, one study found that the odds of a s- of a facility receiving the most severe inspection outcome are over 250% higher for unannounced inspections, which just makes sense, doesn't it?

You clean up when you know people are coming over.

The only reason this studio is so clean is because I knew you were all coming here today.

Otherwise, this place would be a complete pigsty. And by the way, I mean that literally.

I run a wet market here the rest of the week.

I, I'm just trying to get out ahead of any Paramount budget cuts.

And, and when the FDA has actually done unannounced inspections, the results have sometimes been terrifying.

Investigators cited Hetero, a major maker of HIV, cancer, and neurological drugs, for running an unregistered testing lab and, somewhere in this village, storing critical ingredients in an undisclosed warehouse.

When FDA inspectors arrived, workers ran and locked the gates- ... refusing entry for two hours.

Once inside, inspectors found bird droppings on storage units and lizards and cats among active pharmaceutical ingredients.

Wow, there is so much there.

I don't even have time to get into the fact that the company is called Hetero- ...

which sounds like the name of a fitness studio Pete Hegseth will inevitably open after he leaves- ... the Defense Department.

And yeah, yes, Pete, that is a great logo, and, no, you can't have it.

But clearly you wanna be able to assume your medication's being handled in pristine conditions with high safety standards

and not in a lizard and cat infested bird's toilet.

And if you are thinking, "I didn't even realize that lizards and cats hang out together-"

... then

you are clearly unaware of Junior and Atlas, a real lizard and cat duo who live together in an apartment and, crucially, are best friends.

Take a look.

Atlas wants to rub up against him.

Atlas, I don't think he wants to love on you today.

She wants to follow him. She wants to make sure that he's going where she wants to go.

The neatest thing to see is what they enjoy doing together and their friendship as they get older, too.

They're in love with each other.

What a beautiful friendship, full of love, joy, and a palpable sexual tension.

Is, is it just me or are they giving off strong will they or won't they vibes?

Anyway, at this point you might be thinking, "Well, if things are really bad, the FDA bans imports from factories that fail inspections, right?"

Well, sort of.

The problem is, with so few manufacturers making certain drugs, bans can lead to critical shortages.

So what the FDA will sometimes do is create carve-outs for certain drugs in short supply, even if they are coming from a factory with known quality issues.

Take what happened at that Intas factory where workers were pouring acid on test results.

Production there understandably got suspended,

but that had real consequences because that factory made, among other things,

50% of the critical chemotherapy drug Cisplatin used in the US.

That is what led to the drug shortage that that woman was talking about earlier,

and it wasn't even the only Intas factory with problems.

That same year, another plant failed inspection and the FDA barred both of them from shipping drugs to the US.

But here is the thing,

because it was so worried about creating shortages, the FDA simultaneously granted those factories more than 50 exemptions,

meaning they could keep sending certain drugs here.

Now, the FDA says those carve-outs came with requirements that Intas hire third-party, third-party experts to do additional safety testing,

and Intas insists that it did that.

But it's a little weird to happily trust a manufacturer with that level of responsibility

when you've already, you know, caught them dousing test records- ... with fucking acid.

And all of this is obviously very worrying, or it would be if it was more widely known.

But the thing is, the FDA's actually kept its drug exemptions largely hidden from the public and from Congress,

with the agency's former top drug official justifying that by saying the information would've caused some kind of frenzy.

Oh. But that frenzy would've been for a reason.

Because I admit, sometimes what you don't know really doesn't hurt you, like the fact that the McRib is actually made out of squirrel meat.

But this is not that.

Now, the FDA insists it works to ensure all drugs meet a high standard and that they recognize areas where authority could be strengthened and are actively working to address this.

And to be fair to the FDA, right now this is clearly a struggle.

They're having to play Whac-A-Mole with a bunch of bad actors, and they really have no good choices 'cause certain drugs are critical, so you don't want there to be a shortage.

And while you obviously don't want drugs coming out of dangerous factories,

you also don't wanna scare people away from taking their meds altogether.

In fact, even a former FDA inspector admitted when testifying to Congress that there have been times when he's prioritized keeping people calm over telling them the whole truth.

You don't wanna cause unnecessary panic in, in someone.

And, you know, a lot of people ask me before they, they'll take it, they'll, they'll give me a call or send me an email like, "Hey, uh, you, what do you think about this one?"

And I'll give them advice.

And to be honest, over the years, sometimes I have to fake that advice because I know there's no alternative,

and I'll have to just send a positive email when, in fact, inside I know that that's, that's not, that's not the truth.

Yeah, that's not great, is it?

And a televised congressional committee is a hell of a time to come clean about that.

Just spare a thought for any of his friends watching. Who had sent him one of those emails.

You're relaxing at home, watching a congressional hearing on the generic drug supply chain, as we all like to do, and you're just about to pop a pill in your mouth- ...

when suddenly he says that shit.

What the fuck, Peter?

You lied to me.

So what do we do?

Well, unfortunately, there is no one big solution here.

Instead, experts point to a lot of partial ones.

For instance, for our most important medicines, we may want to consider onshoring or even friendshoring production of those drugs and their active ingredients, meaning

that we choose to produce them ourselves or ensure that allied countries do it.

That might be wise in case we ever have, I don't know, a crazy president who starts a massive trade war with China for no fucking reason,

but don't worry, I can't see that ever happening.

Meanwhile, when it comes to overseas factories, we should probably be making sure that the FDA has enough resources to properly inspect them

and to test drugs from manufacturers of particular concern.

And to its credit, the FDA promised last year to do more surprise inspections overseas.

Although, recent layoffs there will probably complicate those efforts, especially given dozens of people who help coordinate travel for investigators like that have been let go,

which is both very stupid and completely unsurprising, given it feels like RFK's ultimate vision for the FDA is just one small office where a rabid bear does pull-ups all day.

As for what you can do as a consumer, well, the first thing I should say here is, and I know this is gonna sound ridiculous given everything you've seen so far,

if you are taking a drug right now, it is really important for you to keep doing that.

The majority of generics are safe.

The last headline anyone needs right now is, "Soap Opera Star John Oliver Tells Audience to Stop Taking Their Meds."

'Cause only the first part of that is true.

That said, it is worth paying closer attention to what you are taking, and that is advice that some doctors, like this one, have found themselves giving.

Years ago, I didn't know this, and people would come in,

and they maybe had been stable on their medication for years and years,

and then they come in and they say, "I don't know what's going on.

I'm having a lot more anxiety," or, "I'm getting headaches or stomachaches."

Now, years ago, I used to probe with those questions, "What's going on?"

Really asking a bunch of questions to figure out what's happening.

Now, the first question I ask is, "Does your pill look the exact same?"

And I would say probably 75% of the time, the issue is that there's been a change in manufacturer, and that's causing them to have issues with the way they're responding to the medication.

Right. If you are noticing issues when it comes to how your medication is working, maybe the first thing to ask yourself is, do your pills look any different?

A- and the second is, did your new prescription bottle randomly come with a free lizard inside it?

Or if your past prescriptions always came with a lizard, was your new bottle suddenly lizard-less?

And if the answer to any of those questions is yes, that might mean your pill manufacturer has changed.

And look, if you are worried about a drug that you are currently taking, ProPublica recently built this tool, Rx Inspector, which could be useful for

you. Very basically, just look on the packaging that your pills came in a- and see if you can find the manufacturer, because if you can and then you then search for that manufacturer on their

site, you should be able to find more on the specific factory where your drugs were made, its inspection history, and even inspection reports if they are available.

But obviously, in an ideal world, we shouldn't have to be looking up international inspection reports- ... just to feel confident in the drugs that we take.

Ideally, we'd have a reliable rating system for drug quality that everyone could see and that could be used to incentivize the production of better generics.

But until big changes like that happen, more people should probably be aware of some of the issues here.

And I can frankly think of no better way to do that than to welcome some of my friends. Hey, guys.

Hey. Hey. Good to see you. No, no, no. We're not candy. Even though we look so fine and dandy.

No, no, no, I get, I get it.

You're not candy.

No, you, uh, you've made that very clear.

You're, you are generic drugs, and you are all very important.

Yeah. Yeah. That's right, John. Yeah.

And you should be a lot more careful about how you make us.

Yeah, that's fair.

And inspect our factories more often.

Yep, yep. And also, we're not candy.

No, I, I get that. You, you've, you've made that emphatically clear.

Uh, is there anything else you guys would like to tell everyone right now?

Sure. Okay. Go for it. Oh. Oh. Oh.

This is serious. It is.

You don't want your drugs to be mysterious. Mysterious. Oh.

Yes, we're cheaper. That is true.

But we shouldn't also cost you a peeper.

Use your brains.

That's right. Fix your supply chain. Right.

So we can help you.

Exactly, guys. Exactly. That's perfectly put. Exactly.

Yeah. Yeah. So, so I can help your heart transplant.

Yeah, that sounds good to me.

And I can cure your depression.

Good luck with that.

And I can help Grandpa get a boner.

Generic drugs, ladies and gentlemen.

Thanks, guys. Great job. Thank you. Thank you.

And now this.

Da, da, da, da, da, da. Ba, da, da, da, da.

Is that the Jet Stream I hear?