How an HIV Miracle Drug Vanished

In 1998, a pharmaceutical company suddenly lost the ability to make their lifesaving HIV drug at one of its production facilities. Then that failure spread to the company’s analysis labs. Then it spread to the other production facility, and within months the lifesaving drug had effectively vanished from the entire planet. And this wasn’t the first time something like this had happened. How does a chemical just… disappear?

#chemistry #medicine #crystallization #ritonavir

Producers:
Andrew Sobey
Elaine Seward
Darren Weaver

Writer:
George Zaidan

Hosts:
George Zaidan

Executive Producer:
Matthew Radcliff

Scientific Consultants:
Stephen R. Byrn, Ph. D
Leila Duman, Ph.D.
Brianne Raccor, Ph.D.

Executive in Charge for PBS: Maribel Lopez
Director of Programming for PBS: Gabrielle Ewing
Assistant Director of Programming for PBS: John Campbell

Reactions is a production of the American Chemical Society.
© 2024 American Chemical Society. All rights reserved.

Sources:
Ritonavir

Ritonavir: An Extraordinary Example of Conformational Polymorphism

Dealing with the Impact of Ritonavir Polymorphs on the Late Stages of Bulk Drug Process Development

Molecular, Solid-State and Surface Structures of the Conformational Polymorphic Forms of Ritonavir in Relation to their Physicochemical Properties | Pharmaceutical Research

Ritonavir Form III: A New Polymorph After 24 Years

Supersaturation Tower

(IUCr) Why don't we find more polymorphs?

Facts and fictions about polymorphism

Disappearing Polymorphs Revisited

NORVIR Update

Polymorphism & Seeding: II. Case Studies

Ritonavir: The Polymorph That Revolutionized Drug

Disappearing Polymorphs

The Predictably Elusive Form II of Aspirin

Crystal Polymorphism in Chemical Process Development

Open questions in organic crystal polymorphism

Microgravity

Tips for Taking RTV

The Best Way to Temper Chocolate

Compound Interest: The Polymorphs of Chocolate

How many more polymorphs of ROY remain undiscovered

Ostwald Rule of Stages─Myth or Reality?

How to Grow Sodium Acetate Crystals

Supersaturated Sodium Acetate Crystallization

Crystallization by Antisolvent Addition and Cooling

Effect of ultrasound on the kinetics of anti-solvent crystallization of sucrose

Ritonavir Form III: A Coincidental Concurrent Discovery

The History of HIV Treatment: Antiretroviral Therapy and More

Recrystallization and Melting Point Analysis

Crystallization of Sodium Acetate from a Supersaturated Solution

Ritonavir: The Polymorph That Revolutionized Drug

Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

Inconvenient Truths about Solid Form Landscapes Revealed in the Polymorphs and Hydrates of Gandotinib

[RealityMeltdownx]

4:47 Wasnt that an "Office Space" reference and not "The Office"?

[gellax]

This is the chemistry equivalent of having your code working, accidentally breaking the project, rolling back to a working version, and then still having the same error message.

[ScienceNotFaith]

I am a pharmacist and worked in the HIV clinic. I remember being told that RTV was no longer available as a capsule and only the liquid was available. Patients hated it. We weren't told why, just that production issues were the cause. Now, many decades later, I learn why. Thanks for the information.

[MetroAndroid]

Imagine you need a drug to live and suddenly no one can make it anymore because all known batches of it turned into goop overnight, and now the reaction to make it just makes goop.

[claudiuspulcher]

"hired a new student by phone, prohibited her from visiting the old lab or meeting anyone from the old lab, had her go buy all new glassware..." today this would be the start of a "fake job bad check" scam

[RabeHK]

I work as a chemist for a large pharmaceutical company and we had a very similar case just a couple of years ago. Once we had the wrong polymer we had to switch buildings, technicians and everything... No glassware, no nothing was allowed to go in the other labs. I still think it is strange with all the hygiene and safety that there were particles somewhere in the air out wherever that caused every crystallization to produce the wrong form afterwards

[stefanradojkovic]

Hi there! I'm a synthesis chemist technician working in the exact same plan in Italy where the production of ritonavir took place. Well, at least while it lasted 😂 last year we attended a seminar/course on polymorphism by our lead solid state expert, explaining and telling us this whole story, from start to finish, and all the troubles and infinite headaches that this situation brought upon our company 😅 really interesting indeed how such a small change in crystallization can bring so widely different results.
If you have any questions or curiosities i can answer feel free to ask!
(Company name was Zach - Zambon Chemicals, but now the same production plan here in Italy is owned by FIS - Fabbrica Italiana Sintetici) 😁

[operands]

Beyond fascinating. Those scientists probably lost their minds trying to figure it out. This is one of the best spooky stories I've ever hear.

[amarug]

I had no intention of watching this video, I am not a chemist, but your presentation was so captivating, I watched it. Fascinating!

[BradSchmor]

I'm a Ph.D. synthetic chemist and I remember when this happened to ritonavir (I was a graduate student at the time). I later worked for a CRO (contract research organization) who had people entirely dedicated to polymorphs - deliberately trying to induce different polymorphs of drug candidates - to attempt to front-load this sort of problem.

I'm not sure I like the comparison of charcoal to diamond, as allotropes are covalent bonds. When I saw that I immediately began to think of chocolate as an example most people are familiar with - and then you went there.

[TheNimaid]

So this video made me realize over and over again that real chemistry is crazier than any sci-fi stuff you see in Hollywood.

[johnford]

Excellent presentation. I'm a Ph.D. analytical chemist with 30+ years of experience. I knew about polymorphs and their importance in the pharmaceutical industry, but was unaware of the ritonavir connection. Thank you for another excellent show.

[Amy-xvsp]

Wow this is so fascinating. As a biologist it reminds me of prions. Just the presence of that misfolded structure infecting all other molecules and then causing them to switch to confirmation 2 as well, makign them so infectioud that just powder of it on peoples clothes could infect another facility and ruind their entire batch.

[MatDotUToob]

I had heard a similar story/urban legend about glycerin in the game "999: Nine Hours, Nine Persons, Nine Doors" and I thought it had to be completely made up. Apparently that specific case was somewhat overblown over the years, but it's WILD to me that the whole "crystal virus" incident is something that actually happens in real life. Incredibly fascinating stuff.

[antona.a.autzen]

Had this happen in a lab I worked. For months, a catalyst was a viscous liquid when purified. One day, it decided to ba a solid, and every prep thereafter was a crystalline solid.

[Yaivenov]

So the plot to Ice-IX came true in a specific instance. Terrifying.

[Vatharian]

There is a Sci-fi novel, in which scientists found a script encoded in a cosmic background radiation. After laborious analysis they found it contains perfect description of all laws of physics - all we knew, and more, which opened a door to rapid technological progress with inventions bordering magic. But at some point some of these inventions - in few cases right after first use, just stopped working, and it was later discovered, relevant sections in the script were just gone. Something was actively monitoring and modifying universe to restrict humanity.

This novel instantly came to my mind when you mention it couldn't be made anymore, followed by "aaah, contamination.".

[mcsabas]

I’m going to study chemistry at uni but am currently on a gap year and doubting why I even picked chemistry in the first place. Thank you for reminding me how great chemistry

[JimWARNOCK-rs]

One of the best videos I’ve seen on YouTube. Informative, educational, and even entertaining! Information is presented at a perfect pace! Not too fast; not too slow.

[oophyte]

Can't believe you did not draw the parallel to prions.