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FDA Unveils Biosimilars Guidance
ananyo writes "The U.S. Food and Drug Administration has released its long-anticipated draft guidance for drug makers interested in making generic forms of biological drugs such as enzymes and antibodies. The move could open the door for cheaper versions of some of medicine's most expensive drugs, but it is still unclear how many companies will be willing to tackle the challenges and uncertainties of making 'biosimilar' drugs. Copying biological molecules is a stickier proposition than making ordinary generic medicines because proteins are typically much larger and more complex than small molecule drugs. They are also often produced in cell cultures, and even small variations in how the cells are grown can change the properties of the protein produced."
I'm confident that even with expensive and difficult processes it'll still happen. Look at some of the treatments for Chron's Disease- there's a med that a friend of mine uses that's massively complex and extremely expensive, but allows her to essentially live a normal life. It's thousands of dollars a month, so something half the price could still be very profitable if it still works properly.
Certainly a lot of generics manufacturers might avoid the more complex drugs, but plenty will take a look, and possibly new companies will get in on the act too.
Do not look into laser with remaining eye.
Have a look at filgrastim, and the epoetins - there are already some biosimilars on the market, or at least there are in the UK. Interestingly, the original filgrastim (from Amgen) is the cheapest of all of the options in the UK (there are alternatives from Teva, Sandoz, Ratiopharm and Hospira). However, this is actually because the presence of multiple biosimilars has brought the price of all of the options down - when there were only two biosimilars, in 2010, one of the biosimilars was the cheapest option, and they all cost at least £13 more for 30 million units (300mcg) than the price today. Competition is a powerful driving force for pricing in the pharmaceutical industry.
If you want biological molecules for drugs, the last thing you want to do is try to synthesise them Why not just open up yeast to genetic engineering and have the modified yeast create your molecules by the ton? Once you have the research and modifications done, you can grow those yeasts for pennies.
Understanding the scope of the problem is the first step on the path to true panic.
Do you really think that in this day and age, that there are any people left who find that meme even remotely funny?
Why waste your time?
For pharmaceuticals, small-molecule drugs and biologicals have long been regulated under two different tracks, for reasons both historical and practical (including the problem that biologicals simply aren't amendable to the kind of complete analysis you can do on small molecules). Sometime ago (maybe about a decade or so?) back, the FDA decided to modernize things, and start applying principles from the former track to the latter. There were a lot of facilities that used processes little-changed since being invented back as far as the 50's and 60's, that were shuttered; recent product and vaccine shortages happened not long after the number of manufacturers dwindled (for some products, from double-digits down to 1-2 sources).
Anyway, wanted to give an example of the limitations of characterizing biologicals. A while back, there was a case involving an Erythopoetin drug (used to treat certain kinds of anemia). The FDA mandated a change in manufacturing, in a big push to get rid of animal-derived raw materials (in this case, anything bovine-derived, following the mad-cow scare). The protein drug in the new formulation was found to be exactly the same by every testable parameter -- sequence, folding, everything else -- and seemed to function the same when examined in animal and human subjects. But when it was released for use in the field, there was a sudden spike in cases of pure red blood cell aplasia (where the body simply stops make any RBCs). Little details in the manufacturing process can sometimes make an enormous difference.
To use an analogy, biologicals are sometimes like arcane and kludgy code that nobody fully understands; once you somehow get it working, there is good reason to not to poke it, and to fear that it might break in somebody else's hands.
Anecdotally, a lot of people (including many who are well-educated about the pharmacology behind drugs) swear there is a difference between some generic and brand drugs, and between the different generics. Sure, most of the time it's a placebo effect, but there are legitimate factors that can cause real differences, such as different binders and fillers being used, that can change the rate of absorption of the active ingredient, or even cause unrelated side effects or affect the bioavailability of the active ingredient. It will be interesting to see if these new, more complex molecules will widen the (perceived or real) differences between brand and generic medications.
Surely 3D printing of molecules, maybe in free-fall on a private space station is the future?
I wasn't. I was wasting yours. The same basic comment got modded UP in a different thread a few days ago, just confirming my theory that /. is moderated by dickheaded pieces of shit who will score -1 anything by an AC but that will get modded up if it comes from an account logged in. (Not the first experiment of this type incidentally, and again, same results.) /.'s mods are biased, and the site is a time-killer. If I didn't have time to kill, I wouldn't come here, because otherwise, this 'blog' is mostly useless.
Slashdot. News for Turds, Shit That Splatters.
Couldn't have put it better myself. Out, bitches.
Since there seems to be a bit of confusion here, allow me to explain (inadequately I'm sure) why different manufacturing processes for biologics result in non-identical molecules even though the DNA sequence and folding of the amino acids is the same.
One of the primary differences is in the glycosylation of the protein. This is where sugar groups of various structures are attached to the outside of the protein and act as a sort of label to the body (distinguishing self from non-self proteins), and even within the cell itself (identifying where the protein should be placed inside of the cell). Different organisms each have their own system for attaching and interpreting these sugar groups. For instance, typical yeast Saccharomyces cerevisiae has a glycosylation profile that will cause the human immune system to attack it eventually - which will make you have an adverse reaction not only to the drug that you're taking, but any other drug produced in the same organism. The yeast Pichia pastoris has a glycosylation profile that is superficially similar to a human one, making it less likely to cause an adverse reaction, but the organism is locked down by patents. Furthermore, there's some evidence that the glycosylation is affected by the health of the cells in the culture, and the media that you're culturing them in. Frequently we'll just coat the proteins in polyethylene glycol and hope for the best.
The other place that variation occurs is in the purification processes that are used to separate the drug molecules from everything else. Many of the purification processes will alter the glycosylation profile or the folding of the protein. They're also generally rather lossy, in that the purer the protein you want, the less of it you'll end up with, and the more it will cost. We used to attach tags to the proteins so that they were easier to purify (his6 was a common one), but then there were concerns that the tag itself would become the target for an immune reaction (which, like the glycosylation, would make a person resistant to not only the drug they were taking, but any other drug that used the same tag), so the practice has been mostly discontinued.
The simple fact is that biologics will always result in mixed batches of molecules, and different manufacturing processes do directly affect that mix. The trick for biosilmilars will be to ensure that their mix is functionally similar enough to the original one; which will likely require clinical trials - meaning that cost savings won't be nearly so drastic as it is with small molecule drugs. While we've figured out how to make DNA translate to a protein of our choosing, we're not nearly as knowledgeable about how to manipulate sugar groups in a similar manner. Progress is being made for sure, but we're not there yet.
"Operating systems suck: you're better off using only the BIOS" --trainsaw.com
I got to interview the Salk Institute's Ronald Evans about exercise, training, and fitness -- he's a cell biologist and looks at how drugs might mimic the *signals* of exercise without a person actually exercising. In fact, there's a good candidate: the drug AICAR does just this, making cells believe they've exercised without all the, you know, sweating and such. The body ramps up its burn rate and you lose weight and gain muscle. Unfortunately, Evans says not to look for AICAR anytime soon -- it's generic and injectible. Any company that puts $100m into development would face immediate market competition. And the market doesn't want to inject. It's a great drug -- but we'll never see it.
GeekDad, TED speaker, Wipeout loser, author of Brain Trust