Understanding Drug Substance: Small Molecules vs. Biologics
G?k?ehan P.
Pharmaceuticals Expert with 13+ years experience | R&D | Manufacturing | Quality Assurance | Market Development | Small Molecules | Drug Product | Clinical Trial Batch
As you might have read the latest article on “Pharma World” with your newsletter, you would be aware that pharma industry is a big and complex industry considering several technologies and manufacturing methods, along with the different areas of expertise. ?
In this article, I will concentrate on two different “Active pharmaceutical ingredients” which are divided by name with their molecule sizes.
What are small molecules as drug substances??
Small molecules are chemical compounds with molecular weights below 900 Daltons. Most drug substances are small molecules, and their small size allows them to diffuse across cell membranes so that they can reach intracellular sites of action. Despite the development of more targeted drugs, small molecule drugs are immensely popular, and account for?90% of drugs in the market. ?
Examples of common small molecule drugs include aspirin, penicillin, paracetamol, ibuprofen, naproxen, metformin, esomeprazole etc. ?
What are large molecules, so called biologics??
Biological drugs?are drug substances that are manufactured or extracted from living organisms. These drugs can consist of genetic material or proteins such as?hormones?or?antibodies. The therapeutic target of a biologic is always a gene or a protein.?
These are typically larger in size than small molecule drugs, with a single molecule consisting of?anywhere between 200 to 50,000 atoms. ?
Some examples of biological drugs include:?
Protein-based biologics and devices are used to treat everything from wrinkles to rattlesnake bites and range from natural protein sutures to fibrinogen coagulant factors. Biotechnological applications in healthcare encompass prophylactic agents,?in vivo?diagnostic tools, and therapeutic products. Biotechnology provides imaging agents and molecular diagnostic tests for detecting a wide range of health problems, from excessive LDL levels to drug-resistant HIV strains.?
What are some differences between small molecules and?biologics??
1.Synthesis method: Other than the obvious difference of molecule size, the main difference between these two therapeutic modalities is that while small molecule drugs are chemically derived, biologics are extracted from living organisms.? ?
2.Characterization: Unlike small molecule drugs that are characterized by their specific chemical composition, it can be difficult to determine the exact chemical composition of biological drugs because they are often large, complex molecules. Instead, these are characterized by the process by which they are obtained.?
3.Administration route: Small molecule drugs are typically administered orally, therefore a lot easier to administer than biological drugs.?Biological drugs, on the other hand, are not as stable as small molecule drugs. If they are consumed orally, they degrade in the gastrointestinal tract. As a result, biological drugs are?typically administered?by injection or infusion.???
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4.Patient Compliance: While small molecule drugs, such as tablets, capsules, powders, granules etc.?can be taken by the patient themselves, biologics are only available as intravenous injections, which adds burden to patient compliance and cost to hospitals.?
5.Stability: A typical medicine with small molecules as API can have a two to three years of shelf life, which is only possible due to the stability of these molecules. On the other hand, vaccines and other medications manufactured with biologics have much shorter shelf life caused by less stability of the drug substance itself. ?
6.Cost factor: One of the factors that currently hinder the use of biologics is their exorbitant cost of development and manufacturing. Unlike small molecules, proteins contain variable complexes especially in terms of surface glycosylation and folding patterns making the manufacturing process incredibly complex.?
7.Side effects: Biological drugs are highly targeted drugs. They don’t bind to non-target molecules, and as a result, lead to fewer side effects.?
And a few more differences such as regulatory approach and manufacturing of the final drug product should be considered on these two therapeutic modalities.?
Currently we all can observe, how fast pharma world evaluating with its technologies to provide patients with medications for several therapeutic areas. While solid oral dosage forms remain very popular among patients, some niche drug products are preferred for specific diseases or even rare diseases. This being sad, it appears to me that both small molecules and large molecules will continue to coexist in the next decades. And Biotechnology will definitely stay sophisticated and charming for the Young Scientists in the world!
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Yours truly,
G?k?ehan Pürs?ken
Resources:
Shaping the future of personalized medication | Founder and CEO of PrivMed? X AB | Senior Managing Director of kg-pharma AB
1 年Hi G?k?ehan, very interesting post, I really enjoyed reading the article for a better understanding of small molecules and biologics ! ??