Small Molecule Pharmaceuticals: Still Crucial in an Evolving Industry

A small molecule is defined as one that has a molecular weight of less than 900 daltons. In the area of pharmaceuticals, the term is used to mean molecules that bind to certain biological macromolecules and can play a role in regulating a particular biological process. The upper size limit of 900 daltons has to do with the digestive system’s intracellular absorption ability. While molecules larger than 550 daltons may be more challenging to absorb, there are some up to 900 daltons that successfully cross barriers.

Many drugs used to treat medical conditions are small molecule pharmaceuticals. And while the makers of pharmaceuticals are increasingly focused on the testing, production process development, and marketing of biologics, small molecule pharmaceuticals are still among the leaders in annual sales. Some of top sellers include:

• Ledipasvir/sofosbuvir (Harvoni)
• Lenalidomide (Revlimid)
• Sofosbuvir (Sovaldi)
• Fluticasone propionate/salmeterol (Seretide, Advair)
• Rosuvastatin (Crestor)

In fact, many experts believe that the future of the small molecule pharmaceuticals industry is bright. FDA approvals for what are known as “new chemical entities” (NCEs) are among the highest since the late 1990s, and there are a wide range of molecules at every stage of research and testing. Consequently, production process development and the engineering and design of facilities to support it are at high levels as well.

Small Molecule vs. Large Molecule Pharmaceuticals

Small molecule pharmaceuticals have a number of advantages over large molecule drugs. This includes:

• Strong effect at low dose. Small molecules can be developed to have a significant therapeutic impact at doses often below 10 mgs, and in some cases much lower than that.
• Cost-effective production. Because they have smaller amounts of their active pharmaceutical ingredient (API), and with ongoing advances in chemical manufacturing technology, small molecule drugs have a lower cost relative to their efficacy.
• High quality. The technology for researching, developing, testing, and producing small molecule pharmaceuticals is very advanced and enables pharmaceutical companies to achieve and maintain very high quality standards to ensure that drugs have exceptional reproducibility and the expected efficacy.
• Oral delivery. As noted above, the small size of small molecule pharmaceuticals means they can be absorbed easily by the body. Consequently, they can be produced in oral form and do not require injections. This results in increased adherence to medication regimens in patients as well as lower overall cost of administration as compared to large molecule pharmaceuticals.
• Precise control. The extensive expertise around small molecule drug production process development continues to grow, allowing manufacturers to develop formulations that accurately target specific sites and are released over well-controlled time frames.
• Simpler clinical trials. Process development and production of materials for clinical trials is less costly, as is the shipping and storage of these materials since they typically do not need the cold chain assurance required by large molecule drugs.

One disadvantage of small molecule pharmaceuticals is that their simplicity leaves them more open to competition from generic equivalents. Larger, more complex drugs are harder to replicate and therefore face less competition.

The Future of Small Molecule Pharmaceutical Manufacturing

The commercial history of small molecule pharmaceuticals goes back to the late 1800s, when the drug branded as “aspirin” was first sold. Today, approximately 40,000 tons of aspirin are consumed annually worldwide. And researchers continue to find new uses for this versatile medication. Anti-inflammatory drugs that are so common today also have a long history. They were first produced in the late 1940s and their use continues to grow.

Both cases point to the fact that predictions of the decline of small molecule pharmaceuticals may be faulty. In fact, as far as small molecule APIs go, the need for particularly potent materials like hormones, cytotoxics, and very low-dose compounds is growing rapidly. And because facilities that produce these substances require specialized handling and containment capabilities, the insights of engineering and design firms like APECS on everything from process development to storage are in high demand as well.

Our full-service engineering and design firm can help you develop a cutting-edge small molecule pharmaceuticals plant. We have 30+ years of experience helping our clients meet their engineering, design, project and portfolio management, capital planning, and environmental health & safety needs. Contact APECS, Inc. today to learn more about how we can help with your pharmaceuticals facility needs.