Generic Drug Development

Generic Drug Development
Generic drug development begins by first understanding how the name brand pharmaceutical works. In a generic, the active pharmaceutical ingredient and delivery system (whether IV, bolus, spray, or tablet) must be the same as in the name brand, but the formulation, color, excipients, and the casings of the drug may differ. As an example, Tylenol is the name brand of one of the most common used drugs on the market. However, many people purchase its generic alternative acetaminophen, which is what the active ingredient or compound is called.   

When a new pharmaceutical is in development and ready for clinical trials, the company that is producing it must file a New Drug Application (NDA). Conversely, when a generic is being produced, an Abbreviated New Drug Application (ANDA) must be filed. Through the ANDA, the manufacturer must demonstrate to the FDA the equivalency of the generic to the brand name pharmaceutical. Read about what the manufacturer must demonstrate to the FDA to secure its approval in “Demonstrating Generic Drug Equivalency.”  

While this ANDA process can take several years, because the name brand drug has already undergone preclinical and clinical testing, these steps do not have to be repeated for generic drugs. This reduces the time and cost of generic drug development, which lowers the cost of the drug for the consumer, thereby making them more accessible to more people. 

Optimizing Drug Reactions at MRIGlobal
When developing a new pharmaceutical drug, chemists will screen several chemicals that have shown promise against whatever disease they are researching. Researchers will use an assay that has been created to analyze the impact or inhibition of those chemicals on the disease they are investigating. Once they get a hit, they then start to develop a library of similar compounds with the same base structure. Using these compounds, they will go through a second round of testing to select a few that are most promising. This testing and optimization can go through several rounds until a single compound shows a lot of promise in treating a disease. Throughout these initial tests, they are only synthesizing each compound on the milligram scale, as they don’t need much product to perform such tests. Also, the procedures they are using may not be optimized and often have poor yields. Once a drug with promise has been found, process optimization occurs so that the compound can be synthesized with a good yield and at a large scale. 

Medicinal chemistry combines chemistry, biology, and pharmacology to design and develop new drugs and improve existing ones. At MRIGlobal, our synthesis team uses this approach in the development of synthetic routes for target molecules. We optimize procedures for medicinal chemistry routes (milligram synthesis) so they can be replicated on a manufacturing scale (kilogram synthesis).   

We initially perform reactions on a milligram to gram scale, slowly then scaling the reactions by increasing them 10-50 times the original size. This allows us to determine whether our reactions are going to work and by efficiently using our synthetic intermediates without much waste. Once we have successfully shown that we can synthesize materials on the kilogram scale, then we start working on providing materials for toxicology and clinical trials.    

Optimizing reactions can target several criteria to make the synthesis more efficient and cost effective. A few of the main areas that we target for optimization involve the removal of harsh or dangerous chemicals, using better or fewer solvents that don’t have adverse health effects, and rerouting the chemistry to have fewer steps.  

Recently, this has included cGMP manufacturing for a Phase 1 clinical trial for the treatment of methamphetamine use disorders, developing new routes for the treatment of Tuberculosis and familial dysautonomia, and several drugs that involve the treatment of different cancers and Alzheimer’s disease.   

Challenges and Opportunities in Development of Generics
Working in the laboratory to replicate name brand pharmaceuticals is the first step in developing generics, but they also then have to be scaled to work in manufacturing, which presents its own challenges. This can include the formation of undesired products in the reactions that may increase as those reactions form. As with all chemistry, there can also be challenges that cause our reactions to stall or just stop working. Additionally, when using catalyst in scaling up reactions, they can experience catalyst exhaustion, which is when a catalyst can become exhausted to the point where it basically stops working or it doesn’t keep regenerating as it should.  

As an opportunity, the industry is making advances in green chemistry initiatives, prompting a greater focus on what products are going into a reaction. We’re very cognizant of the solvents and reagents used, and making sure that we’re producing efficient chemical reactions, which is called atom economy. Read more about these efforts at “Pursuing Green Chemistry.”  

At MRIGlobal, our work supporting generic drug development aligns with our company vision of being a “leader in providing health and safety solutions within the reach of everyone.” By supporting development of generics, we are helping to lower their cost, which makes them more affordable and accessible to more people around the world.