Active pharmaceutical ingredients or APIs can be defined as the chemicals used to manufacture pharmaceutical drugs. The active ingredient (AI) is the substance or substances that are biologically active within the drug and is the specific component responsible for the desired effect it has on the individual taking it.
Any drug or medication is composed of two components. The first is the API – which is the central ingredient. The second is known as the excipient, which is the inactive substance that serves as the vehicle for the API itself. If the drug is in a syrup form, then the excipient is the liquid that has been used to make it as such.
APIs are generally manufactured through a variety of processes that include:
1) Chemical synthesis
2) Fermentation processes
3) Recombinant DNA
4) Isolation and recovery from natural sources
5) A combination of these processes
The purpose of APIs according to the FDA is to cause ‘pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the human body.
There are however certain APIs that are unknown and so require additional substances that work in conjunction with the API to produce the required effect. This is very visible in herbal medicines in which the API is frequently a combination of several mixtures and/or substances which when used together cause pharmacological activity on the body. In these situations, the API is not a single substance but the culmination of various ingredients.
By drawing these distinctions between APIs and the drugs themselves, manufacturers are able to specialize and pharmacists able to align generic equivalents with brand names. This is of vital important and underlies one of the most solid principles and regulations of modern pharmacy.
The Active Pharmaceutical Ingredient Industry manufactures active pharmaceutical ingredients from raw materials through both chemical and physical means. Depending on the complexity of the molecule required, synthesis of APIs might need multi-step complex chemistry utilizing a range of processing technologies.
APIs are commonly referred to as ‘bulk pharmaceuticals’ and are in fact usually made in places at quite a distance to where tablets, suspensions and liquids are manufactured. Today, the greatest concentrations of API manufacturers are located around Asia, specifically in India and China. This has led to more and more companies to outsource API manufacturing to such places, which has the main benefit of eliminating the need to invest in highly expensive equipment and infrastructure – which on top of everything can also be complicated to install and maintain.
Regardless of where the active pharmaceutical ingredient is made, companies must adhere to strict safety and quality standards set by the country where it will be used. So those APIs manufactured in China or India for use in the United States must still be inspected and licensed by the FDA. Similarly, if the API is intended
for use in Europe, they would need to meet regulations set by the European Medicines Agency. Regular inspection outside the country of use however can prove difficult with counterfeiting and contamination being high on the list of various agencies’ concerns. For instance, since 2008, the FDA has considerably increased its overseas staff as a way of attempting to eliminate these problems. As a result, countries such as India have gained their foothold in the global market and now have around 75 FDA-approved manufacturing facilities for API synthesis.
Today there are more and more calls for API manufacturers to go green – that is to say, to reduce the waste they produce. Every year, large pharmaceutical manufacturers can produce anywhere from 3000 to 5000 tons of hazardous waste each. If one were to ask any reputable API manufacturer how they would like to improve the process, they’d likely say to make the reactions faster, or to make them cheaper. Ironically the first steps in reducing waste from API synthesis would be to reduce the number of reactions required to produce a given molecule. Therefore though the goal may be different, the means turn out to be the same as fewer reactions mean less solvent to dispose of. Another step in going green is to find different solvents and catalysts that are not only more efficient, but are also better for the environment.
Major API manufacturers are also moving away from multifunctional plants and instead opting for specific activities at specific sites. In this way, there are serious concerns as to how any centralized control could function as after all an API manufactured by one company, in one country, with the excipient manufactured in another by a different company, then packaged and distributed by another company altogether makes the route rather difficult to monitor or control.
The current growth in new medical technologies is spurring the demand for APIs worldwide today especially with the increased importation of raw pharmaceutical ingredients from emerging markets. Countries such as India and China, which now supply over 40% of APIs used in the U.S. will double that figure to a whopping 80% in just the next 10 years.