“A one-degree difference in the environment can make the cell react in different ways, and you may have a different drug at the end,” Gouty says. “It’s like if you cut yourself one day, you might bleed for one minute, but for some reason you might bleed for 10 minutes if you cut yourself another day. Living things have lots of variation that we don’t understand and we cannot control.”
When Genzyme attempted to scale up its manufacturing process for Myozyme in 2008, the FDA found that when the process moved from a 160-liter tank to a 2,000-liter tank, the carbohydrate attachments of the enzyme were somehow changed. The company had to repeat its safety and efficacy experiments, and ultimately it had to market the drugs from the larger facility under an entirely new brand name.
“Even within the same company with the same manufacturing process, the product can be different day to day,” Gouty says. A generic manufacturer is likely to have a very different process from the pioneer company, making it even more difficult to create a similar product.
3. Biological drugs pose unique safety concerns
In 2003 Johnson & Johnson learned the hard way that a seemingly small change to the manufacturing process can have devastating consequences. In manufacturing Procrit, a biological treatment for anemia, the company substituted one stabilizing agent for another, which was thought to be safe. Studies later found that 16 percent of Procrit users suffered sudden and sometimes fatal reactions to the drug. After the drug had gone to market, researchers learned that the new stabilizer had unexpectedly reacted with other ingredients, creating substances that caused immunogenic responses and intracranial hemorrhaging in some patients.
Because they are derived from living sources, most biological drugs will be recognized as foreign invaders by the patient’s immune system. It may send antibodies to bind and capture the drug, reducing its efficacy. Sometimes immune reactions to biological drugs can cause fatal side effects, such as organ failure, fever and cancer.
Currently there is no good way to predict how a body will react to a biological drug, says Jeff Mazzeo, a chemist at Waters, a company that designs molecular analysis tools. Bioassays, where a tissue sample in a petri dish is exposed to the drug, “could theoretically tell you how things would act in a biological system,” Mazzeo says. “The problem with bioassays is that they’re extremely variable. They need to be better.”
For these reasons and more, few experts foresee a day when a biological generic could be approved without running clinical trials first. To do so could be irresponsible, Gouty says.
The Federal Trade Commission estimates that generic biological drugs are “unlikely to introduce...discounts any larger than between 10 and 30 percent of the pioneer product’s price.” Nevertheless, those small savings may add up to $300 billion by 2029, according to some estimates, and future technologies that make it easier to assess the structure and function of a protein could add to those savings. “With enough tools and analysis, my sense is it could be possible to have biosimilars approved with relatively small clinical trials,” Kozlowski says.
At the very least, by encouraging the creation of new versions of biological drugs, the new FDA guidelines will give scientists additional opportunities to study protein structures and the ways they influence safety and effectiveness, Schellekens says. “We’re still in a learning process.”
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9 Comments
Add CommentWhen an article make a glaringly incorrect statement like "In contrast, interferon beta—an antibody treatment for multiple sclerosis", it makes it hard to take anything else in it seriously. Interferons and antibodies are 2 very different classes of molecules.
Reply | Report Abuse | Link to thisI thought interferon beta treated the antibodies in MS patients, making them less liable to attack the myelin sheaths. If such is the case, it might be appropriate to call inteferon beta an "antibody treatment?" I was also under the impression that antibodies are not "a class of molecule," but at best, can be referred to as a "collection of classes of molecules." Though I guess that depends on how precisely one wishes to define "collection."
Reply | Report Abuse | Link to thisI have a feeling that this is still going to benefit the general public. There are two costs associated with a drug, the cost of manufacturing and the cost the market will bear. Competition reduces the second cost, research reduces the first cost. The situation as mandated increases both research and competition.
Reply | Report Abuse | Link to thishealth benefits of both are likely minimal
Reply | Report Abuse | Link to thisSome of us think it scandal that 85 years after insulin was first used, there still are not generic insulins. Yes it is complicated, but not all that complicated, and the industry is milking it for all the money they can.
Reply | Report Abuse | Link to thisHow many Daltons does snake oil weigh?
Reply | Report Abuse | Link to thisAlways keep in mind that the medical "profession" is the strongest cartel and the "legal" next. Wither freedom?! (sic).
Complete sentences and clearly enunciated concepts based on facts are not your enemies.
Reply | Report Abuse | Link to thisYou are free to remove yourself from society and avoid all medical care. People that do this tend to die a lot younger but no one is stopping you.
Reply | Report Abuse | Link to thisI was also under the impression that antibodies are not "a class of molecule," but at best, can be referred to as a "collection of classes of molecules."
Reply | Report Abuse | Link to thisHappy new year!
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