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 https://www.chemistryworld.com/podcasts/ritonavir/4011593.article Ritonavir: An Extraordinary Example of Conformational Polymorphism https://link.springer.com/article/10.1023/A:1011052932607 Dealing with the Impact of Ritonavir Polymorphs on the Late Stages of Bulk Drug Process Development https://pubs.acs.org/doi/10.1021/op000023y Molecular, Solid-State and Surface Structures of the Conformational Polymorphic Forms of Ritonavir in Relation to their Physicochemical Properties | Pharmaceutical Research https://link.springer.com/article/10.1007/s11095-021-03048-2 Ritonavir Form III: A New Polymorph After 24 Years https://jpharmsci.org/article/S0022-3549(22)00428-2/fulltext Supersaturation Tower https://www.flinnsci.com/api/library/Download/c931fa405d384d77a06086654faa8ba2 (IUCr) Why don't we find more polymorphs? https://journals.iucr.org/b/issues/2013/04/00/bm5061/index.html Facts and fictions about polymorphism https://pubs.rsc.org/en/content/articlelanding/2015/cs/c5cs00227c Disappearing Polymorphs Revisited https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201410356 NORVIR Update https://www.natap.org/1998/norvirupdate.html Polymorphism & Seeding: II. Case Studies http://pd.chem.ucl.ac.uk/pdnn/mod3/polycase.htm Ritonavir: The Polymorph That Revolutionized Drug https://solitekpharma.com/ritonavir-how-the-discovery-of-a-new-polymorph-changed-drug-development-forever/ Disappearing Polymorphs https://pubs.acs.org/doi/abs/10.1021/ar00052a005 The Predictably Elusive Form II of Aspirin https://pubs.acs.org/doi/10.1021/ja056455b Crystal Polymorphism in Chemical Process Development https://www.annualreviews.org/content/journals/10.1146/annurev-chembioeng-061010-114224 Open questions in organic crystal polymorphism https://www.nature.com/articles/s42004-020-00388-9 Microgravity https://www.nasa.gov/wp-content/uploads/2009/07/315959main_Microgravity_Microscopic_Observation.pdf Tips for Taking RTV https://www.natap.org/1998/k.htm The Best Way to Temper Chocolate https://www.seriouseats.com/the-food-lab-best-way-to-temper-chocolate Compound Interest: The Polymorphs of Chocolate https://www.compoundchem.com/2014/04/19/the-polymorphs-of-chocolate/ How many more polymorphs of ROY remain undiscovered https://pubs.rsc.org/en/content/articlelanding/2022/sc/d1sc06074k Ostwald Rule of Stages─Myth or Reality? https://pubs.acs.org/doi/10.1021/acs.cgd.2c00141 How to Grow Sodium Acetate Crystals https://www.youtube.com/watch?v=2FqlAtWN2vo Supersaturated Sodium Acetate Crystallization https://www.youtube.com/watch?v=nrmQBdYp5tU Crystallization.ram https://www.youtube.com/watch?v=HoMLXFHylt8 Crystallization by Antisolvent Addition and Cooling https://www.intechopen.com/chapters/39142 Effect of ultrasound on the kinetics of anti-solvent crystallization of sucrose https://www.sciencedirect.com/science/article/pii/S1350417721004284 Ritonavir Form III: A Coincidental Concurrent Discovery https://pubs.acs.org/doi/10.1021/acs.cgd.2c01017 The History of HIV Treatment: Antiretroviral Therapy and More https://www.webmd.com/hiv-aids/hiv-treatment-history Recrystallization and Melting Point Analysis https://www.youtube.com/watch?v=iIfmoD-G1qo Crystallization of Sodium Acetate from a Supersaturated Solution https://chem.libretexts.org/Ancillary_Materials/Demos_Techniques_and_Experiments/Lecture_Demonstrations/Crystallization_of_Sodium_Acetate_from_a_Supersaturated_Solution_(Demo) Ritonavir: The Polymorph That Revolutionized Drug https://solitekpharma.com/ritonavir-how-the-discovery-of-a-new-polymorph-changed-drug-development-forever/ Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening https://www.nature.com/articles/ncomms8793 Inconvenient Truths about Solid Form Landscapes Revealed in the Polymorphs and Hydrates of Gandotinib https://pubs.acs.org/doi/10.1021/acs.cgd.9b00162