{"slug":"manufacturing-wave","tag":"manufacturing-wave","variants":["manufacturing-wave"],"description":"Manufacturing technologies and the companies behind them, from small-molecule synthesis to sterile injectables.","count":31,"kinds":{"technology":18,"company":13},"related":[],"records":[{"id":"small-molecule-api-synthesis","kind":"technology","name":"Small-molecule API synthesis","route":"/technologies/small-molecule-api-synthesis/","status":"standard-of-care","tldr":"Before a tablet or a vial exists, the active drug itself has to be made: many chemical steps in reactors, or extraction from a plant, at a handful of factories most patients never hear of. When one of those factories stops, whole cancer drugs disappear."},{"id":"oral-solid-dose-manufacturing","kind":"technology","name":"Oral solid dose manufacturing (tablets and capsules)","route":"/technologies/oral-solid-dose-manufacturing/","status":"standard-of-care","tldr":"Most targeted cancer drugs are tablets. Turning a powder into a tablet that dissolves the same way every time is its own craft, and when patents end the same craft lets generic makers sell the drug for a fraction of the price."},{"id":"sterile-injectable-generics-manufacturing","kind":"technology","name":"Generic sterile injectables (the 2023 platinum shortage)","route":"/technologies/sterile-injectable-generics-manufacturing/","status":"standard-of-care","tldr":"Cisplatin, carboplatin, methotrexate and most old chemotherapy drugs are cheap vials made by very few factories under sterile conditions. In 2023 one Indian plant stopped and American cancer centres ran short of both platinum drugs for months."},{"id":"bcg-vaccine-manufacturing","kind":"technology","name":"BCG manufacturing and the bladder cancer BCG shortage","route":"/technologies/bcg-vaccine-manufacturing/","status":"standard-of-care","tldr":"BCG, the century-old tuberculosis vaccine, is the best treatment for early bladder cancer, but it is a live bacterium that grows slowly and only one company makes it for the United States. Since 2019 urologists have been splitting doses and rationing courses."},{"id":"downstream-purification-chromatography","kind":"technology","name":"Downstream purification (Protein A capture, viral clearance, polishing)","route":"/technologies/downstream-purification-chromatography/","status":"standard-of-care","tldr":"After hamster cells have grown an antibody drug, the antibody has to be fished out of a soup of cells, DNA and viruses and made pure enough to inject. Purification is where much of the cost and many of the bottlenecks of biologics sit."},{"id":"single-use-bioprocessing","kind":"technology","name":"Single-use bioprocessing systems","route":"/technologies/single-use-bioprocessing/","status":"established","tldr":"Modern biologics plants grow cells in giant sterile plastic bags instead of steel tanks, throwing the bag away after each batch. It makes plants faster to build and switch, but it ties the whole industry to a few bag and filter makers."},{"id":"biosimilar-manufacturing","kind":"technology","name":"Biosimilar manufacturing and comparability","route":"/technologies/biosimilar-manufacturing/","status":"standard-of-care","tldr":"A biosimilar is a copy of an antibody drug made by a different company in different cells. It cannot be identical, so the maker must prove the copy behaves the same in the laboratory and in patients. Biosimilars of trastuzumab, bevacizumab and rituximab have cut the cost of these drugs sharply."},{"id":"pharmaceutical-gmp-inspections","kind":"technology","name":"GMP, inspections, Form 483s and warning letters","route":"/technologies/pharmaceutical-gmp-inspections/","status":"standard-of-care","tldr":"Every cancer drug plant works under Good Manufacturing Practice rules and is inspected. When inspectors find problems they write them up (a Form 483 in the United States), and if the answers are poor a public warning letter, an import ban or a court order can follow. Those actions protect patients, and they are also how shortages begin."},{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","route":"/technologies/adc-supply-chain/","status":"established","tldr":"An antibody-drug conjugate needs three separate factories: one growing the antibody, one making the poison and its linker in sealed rooms, and one joining them. Then a fourth fills the vials. Any of the four can hold up the drug."},{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","route":"/technologies/car-t-manufacturing-process/","status":"standard-of-care","tldr":"Each CAR-T dose is a separate factory run for one patient: collect their T cells, activate them, add the CAR gene with a virus, grow them for a week or two, freeze, test and ship them back. The steps, the failure points and the waiting list are all here."},{"id":"allogeneic-cell-banks","kind":"technology","name":"Allogeneic cell banks: one donor, hundreds of doses","route":"/technologies/allogeneic-cell-banks/","status":"phase-2","tldr":"Instead of making CAR-T cells from each patient, take T cells from a healthy donor or from a stem cell line, edit them so the patient's body will not fight them, grow a huge batch and freeze it into hundreds of doses that sit on a shelf."},{"id":"mrna-lnp-manufacturing","kind":"technology","name":"mRNA and lipid nanoparticle manufacturing","route":"/technologies/mrna-lnp-manufacturing/","status":"phase-3","tldr":"An mRNA cancer vaccine is made without cells: a DNA template is copied into RNA by an enzyme in a tank, cleaned up, and wrapped in tiny fat bubbles. For personalised vaccines the whole run is done once for each patient, against that patient's own tumour mutations, in a few weeks."},{"id":"research-reactor-isotope-production","kind":"technology","name":"Research reactors for medical isotopes (Mo-99, Lu-177, I-131)","route":"/technologies/research-reactor-isotope-production/","status":"standard-of-care","tldr":"Most of the world's therapeutic and scanning isotopes are made by putting targets into about half a dozen ageing research reactors and flying the product out within days. When two reactors were down at once in 2009 and 2010, hospitals worldwide ran short of the most used scan isotope."},{"id":"cyclotron-isotope-production","kind":"technology","name":"Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)","route":"/technologies/cyclotron-isotope-production/","status":"standard-of-care","tldr":"Proton-rich isotopes for PET scans and some therapies are made by hitting a target with a beam from a cyclotron. Fluorine-18 is made every morning within driving distance of the scanner; gallium-68 comes from either a generator or a cyclotron; copper-64 and zirconium-89 last long enough to ship across a country."},{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/","status":"phase-3","tldr":"Actinium-225 is the alpha-emitting atom behind the most promising next wave of radioligand therapies, and there is not enough of it. Almost all of it used to come from one decaying stock of thorium in a US national laboratory. New routes use accelerators and old radium."},{"id":"radiopharmaceutical-gmp-release","kind":"technology","name":"Radiopharmaceutical GMP and releasing a drug that decays","route":"/technologies/radiopharmaceutical-gmp-release/","status":"standard-of-care","tldr":"A radioactive medicine loses activity every hour, so it is made to order, tested in hours and often injected before the sterility test has finished. The rules for that are different from ordinary drugs, and the handful of plants that make lutetium therapies have had their own shortages."},{"id":"radiotherapy-equipment-manufacturing","kind":"technology","name":"Linac, proton system and brachytherapy machine manufacturing","route":"/technologies/radiotherapy-equipment-manufacturing/","status":"standard-of-care","tldr":"Radiotherapy machines are built by a very small number of companies. Two of them make most of the world's linear accelerators, a handful build proton systems, and installing, commissioning and servicing a machine is as much a part of the supply chain as building it."},{"id":"medical-imaging-scanner-manufacturing","kind":"technology","name":"CT, MRI and PET scanner manufacturing","route":"/technologies/medical-imaging-scanner-manufacturing/","status":"standard-of-care","tldr":"The scanners that find and stage cancer are built by five companies in a dozen factories. Detectors, superconducting magnets and the helium that cools them are the parts that run short."},{"id":"sterling-pharma-solutions","kind":"company","name":"Sterling Pharma Solutions","route":"/companies/sterling-pharma-solutions/","tldr":"Sterling is a British contract maker of small-molecule active ingredients, with plants in the north of England and the United States and an ADC bioconjugation site at Deeside in Wales."},{"id":"sartorius","kind":"company","name":"Sartorius","route":"/companies/sartorius/","tldr":"Sartorius makes the bags, filters, bioreactors and analytical instruments that biologics and cell therapy plants run on. Every antibody drug made in a single-use bioreactor depends on it or one of three competitors."},{"id":"hikma","kind":"company","name":"Hikma Pharmaceuticals","route":"/companies/hikma/","tldr":"Hikma is one of the largest makers of generic sterile injectables for US hospitals, including many chemotherapy and supportive-care drugs, from plants in Ohio, New Jersey and Portugal."},{"id":"amneal","kind":"company","name":"Amneal Pharmaceuticals","route":"/companies/amneal/","tldr":"Amneal is a US generic and speciality drug maker with a growing sterile injectables business, one of the companies that stepped in as platinum chemotherapy ran short in 2023."},{"id":"samsung-bioepis","kind":"company","name":"Samsung Bioepis","route":"/companies/samsung-bioepis/","tldr":"Samsung Bioepis develops biosimilars of trastuzumab, bevacizumab and other antibodies, made by its parent Samsung Biologics at Songdo."},{"id":"cellectis","kind":"company","name":"Cellectis","route":"/companies/cellectis/","tldr":"Cellectis is the Paris gene-editing company that pioneered off-the-shelf CAR-T cells with its TALEN editing tools, and makes them at its own plants in Paris and Raleigh, North Carolina."},{"id":"ntp-radioisotopes","kind":"company","name":"NTP Radioisotopes","route":"/companies/ntp-radioisotopes/","tldr":"NTP, part of South Africa's state nuclear corporation, processes molybdenum-99 and other isotopes from the SAFARI-1 reactor and was the first major producer to switch to low-enriched uranium targets."},{"id":"ansto","kind":"company","name":"ANSTO (Australian Nuclear Science and Technology Organisation)","route":"/companies/ansto/","tldr":"ANSTO runs the OPAL research reactor near Sydney and a molybdenum-99 plant that supplies Australia's nuclear medicine and exports, and produces lutetium-177 for radioligand therapy."},{"id":"ire","kind":"company","name":"IRE (Institut national des Radioéléments)","route":"/companies/ire/","tldr":"IRE in Belgium is one of the world's few molybdenum-99 processors, taking irradiated targets from European research reactors, and its IRE ELiT arm makes the Galli Eo gallium-68 generator."},{"id":"nordion","kind":"company","name":"Nordion (Sotera Health)","route":"/companies/nordion/","tldr":"Nordion supplies most of the world's cobalt-60, which sterilises single-use bioprocess bags and medical devices and powers Gamma Knife units, and was the largest molybdenum-99 processor until Canada's NRU reactor stopped."},{"id":"bruce-power","kind":"company","name":"Bruce Power","route":"/companies/bruce-power/","tldr":"Bruce Power runs the world's largest nuclear power station and, since 2022, irradiates ytterbium targets inside a running reactor to make lutetium-177 for ITM, the first commercial medical isotope from a power reactor."},{"id":"nusano","kind":"company","name":"Nusano","route":"/companies/nusano/","tldr":"Nusano is a Utah company building an isotope production plant around its own ion beam technology, aiming at actinium-225 and other therapeutic isotopes that are in short supply."},{"id":"isotopia","kind":"company","name":"Isotopia Molecular Imaging","route":"/companies/isotopia/","tldr":"Isotopia is an Israeli producer of non-carrier-added lutetium-177 and PET tracers that supplies several radioligand developers."}]}