Biologics, biosimilars, and small molecules

When it comes to pharmaceuticals, there are 2 main kinds - your conventional “small molecules” (just like normal drugs like aspirin and Tylenol that chemists make in a lab) & “biologics.” Biologics encompass a ton of things - from vaccines to hormones like insulin to monoclonal antibodies like Humira to gene therapies and stem cell stuff. They’re often proteins, but can also be DNA, RNA, or other biochemicals (even whole blood falls into this class). What unites them all is that they’re produced by biological systems - such as flasks or vats of bacteria or yeast or insect cells. Taking advantage of biology allows scientists to make much more “complex” molecules than can be made through chemical synthesis routes. Because, as great as chemists are, they’re no match for the teeny tiny chemists inside of cells! And molecular biology technology (mainly recombinant biology) has made it possible for scientists to get cells to make designer drugs!
blog: bit.ly/biologics_etc
We can stick the genetic instructions for making custom proteins (or even just normal proteins we want a lot of) into cells and have the cells make or “express” tons of copies of them. But different cells (even the same cells) might modify the copies in different ways (such as adding different sugar chains in different places (differences in glycosylation)). So the end product isn’t “chemically defined.” This is in contrast to small molecules that have known, set, compositions and each copy is identical.
Instead, each batch of a biologic, even the copies of the molecules within a batch, will vary a bit and the drug is never “identical.” It would be impossible to truly “copy” the product, so there can’t be “generics” of them (drugs which have the exact same formula and structure but are made by different companies than the company that first introduced them). But there can be the equivalent - biologics that are super similar in composition to the original and function at least as well (are non-inferior). These super similar products are called biosimilars and they are often cheaper than the original “brand name” stuff.
But they’re typically still much more expensive than small molecules. Because it can be hard to get cells to make some proteins - lots of optimization might be involved and they still might not express to high levels. And then manufacturers have to actually purify those proteins. This is harder than purifying chemicals from synthesis, and can be done to various degrees and vary from batch to batch. As a result of all this, biologics are often expensive and they are regulated differently from small molecules.
Another key difference is that once you purify them you have to keep them happy - and this typically requires storage conditions like refrigeration since biologics are usually more fragile than typical drugs like aspirin and stuff - the “small molecules.” If they can’t even survive sitting on a shelf, they certainly can’t survive a trip through a digestive system full of protein-digesting machinery. So, instead of being able to swallow these drugs as pills, they’re often injected or infused.
So why go through all this trouble? Because the products can be so useful! And we can’t make them without the help of cells, which have teeny tiny machinery specialized in making them.
resources:
Morrow, T., & Felcone, L. H. (2004). Defining the difference: What Makes Biologics Unique. Biotechnology healthcare, 1(4), 24-29. www.ncbi.nlm.nih.gov/pmc/arti...
Makurvet (2021). Biologics vs. small molecules: Drug costs and patient access. Medicine in Drug Discovery. doi.org/10.1016/j.medidd.2020...
Billingsley & Murdock, How Are Biologic and Small Molecule Drugs Different?, Published in GoodRx Health on January 12, 2022 www.goodrx.com/healthcare-acc...
Mullard A. (2021). FDA approves 100th monoclonal antibody product. Nature reviews. Drug discovery, 20(7), 491-495. doi.org/10.1038/d41573-021-00...
Manis. Overview of therapeutic monoclonal antibodies. UpToDate. Last updated March 14, 2022. www.uptodate.com/contents/ove...
Coghlan, J., He, H., & Schwendeman, A. S. (2021). Overview of Humira® Biosimilars: Current European Landscape and Future Implications. Journal of pharmaceutical sciences, 110(4), 1572-1582. doi.org/10.1016/j.xphs.2021.0...
more on insulin: bit.ly/insulin_diabetes_biochem & • Insulin and diabetes b...
more on recombinant protein expression: bit.ly/proteinpurificationtech
more on asparaginase: bit.ly/asparagineasparaginase & • Asparaginase therapy f...
more on monoclonal antibodies: bit.ly/antibodytypesanduses & • Lab antibody considera...
more on phage display: bit.ly/phagedisplay & • Phage display - theory...
more on stereochemistry: bit.ly/alaninechirality & • Alanine biochemistry -...

[@bozfamily10]

Do you have any thoughts on biomimetic molecules? peptoids for example

[@thebumblingbiochemist]

no sorry!