Understanding biologics: How they differ from drugs and why they cost more

You may have already heard about biologics and biosimilars or may have even already been treated with them for your rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and multiple sclerosis. These products include  Enbrel, Humira, Remicade (infliximab), Avonex (inteferon beta-1a), Simponi (golimumab), Betaseron (interferon beta-1b), Tysabri, Cimzia (certolizumab pegol), Herceptin (trastuzumab), Rituxan (rituximab), Neupogen (filgrastim), Neulasta (pegfilgrastim), Orencia (abatacept), RoActemra (tocilizumab), Stelara (ustekinumab), Cosentyx (sécukinumab)  and Leukine (sargramostim).

So what are biologics, how do they differ from more traditional drugs, and why are they so expensive?

Although some biologics have been around for a long time, we are not talking about these first-generation products, which include things like vaccines, blood and blood components. Instead, we are focusing on the newer, second-generation biologics that have come to market only in the past 10 to 15 years or so. Biologics, as the name implies, are derived, in some way, from living organisms. The first-generation products are literally obtained from humans or animals, such as human blood, insulin (often from pigs or cows), or influenza vaccine, the viruses for which are grown in chicken eggs. Second-generation biologics rely, as described below, on biotechnology for their manufacture.

But before that, let’s take a brief look at drugs, which are essentially chemicals synthesized from other chemicals. Although it’s done on an industrial scale, basically they take chemical A and add it to chemical B, mix it up, perhaps heat it a bit, add chemical C, perhaps filter it, etc., etc., until they get the final desired chemical in a pure form. It’s basic chemistry. A little of this, a little of that and voilà you’ve made a drug. And when the patent expires, it’s fairly easy for generic drug companies to do exactly the same thing but at a lower cost (after all, they don’t have to recoup the huge expenses associated with drug discovery, development, clinical trials, etc.).

Because second-generation biologics are complex proteins they can’t yet be made by following a chemical recipe. We just don’t know how to do that. But since all living cells know how to make proteins, that’s basically what they do for a living, so to speak, second-generation biologics are made by exploiting this fact. We “trick” certain cells to make the proteins for us using biotechnology. A variety of cells have been used to make biologics, but the key is that they have to be alive and fully functioning. We’ve used yeast and bacteria (E coli), and even cells that come from mammals. One of the most widely used mammalian cells is called CHO because it originally came from the Chinese hamster (the “O” signifies that the specific cell used came from the ovary).

There are two fundamental requirements for making a biologic. One is that the cells in which the product will be made have to be grown in extremely large quantities. You need huge vats of yeast, bacteria or CHO cells, and they have to be maintained under conditions that allow them to live and to function normally. But if you think that’s complicated, it’s the second requirement that’s the real mind blower. Since the cellular instructions for making all proteins are carried by the DNA in the genes, if you could either isolate or create the right gene you’d have the blueprint that would tell the cell how to make the protein you want. So without explaining all the complex ins and outs of how they actually get the genes, let’s just move to the next step in the process.

Once the scientists have the right gene (the way it works in all cells is one gene = one protein), they use other special techniques to insert that gene into the host cell’s DNA. They start with one normal cell (from the yeast, bacteria or CHO cell line) and literally plug in the new gene where it becomes incorporated and permanent. They also plug in some special bits that basically tell the cell that this gene is super-important and that while the cell should do what it must to stay alive, it should focus all its other energies on following this gene’s instructions for churning out the desired protein. The cell has been “tricked” into becoming a specific protein-making mini-factory. Grow up a large number of these dedicated protein machines and you’re well on the way to having a biologic product ready to be tested in and eventually used by people who desperately need them.

Obviously, the entire process, from getting the gene, to inserting it into the cell, to growing vast quantities of the modified cells, and finally, to siphoning off just the desired protein (and no other cellular contaminants) is amazingly complex, requiring state-of-the art knowledge in molecular biology, recombinant biotechnology and cell culture techniques. This is why biologics are notoriously expensive. The standard drug manufacturing facilities, however new or sophisticated, are wholly inadequate for biologic production. Entire new facilities must be built from the ground up. A wide variety of highly trained scientists is needed to figure out the biotechnology required, and these personnel can’t simply come from the ranks of chemists already employed by pharmaceutical companies. Moreover, the number of people able to be treated with these new products is often relatively small, compared, say, to drugs designed to treat extremely common disorders like high cholesterol or depression. The fewer the people to be treated, the harder it is to recoup the start-up costs.

This, in turn, begs the question as to whether and when there will be less expensive generic versions of biologics as there are with drugs after their patents expire. Even if appropriate regulations can be crafted, it is still an open question as to how much lower the costs will be. That’s in part due to the expense of the manufacturing facilities, which will limit the number of companies able to get into this business, which in turn, will allow those that do to charge more than if there was a lot of competition.

Source: everydayhealth.com
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Are you or have you been on any of these biologics? For what condition? What treatment did you have before switching to a biologic? What are the results?

P.S. If you are suffering with Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis or psoriatic arthritis, you can also take part in a survey we are currently conducting in the field of biologics and biosimilars. We will appreciate your contribution!