When it comes to the pharmaceutical industry, the self-help route does not necessarily apply. Big Pharma, as well as biotech and drug development companies, rely on an intricate network of partnerships in the academic, business and technical realms to get drugs through the extensive clinical trial process and into the market.
Custom synthesis is one of the options open to drug developers in need of active pharmaceutical ingredients (APIs) to make their products effective. If it is impossible or impractical for a company to make these molecules and compounds in-house, a chemical specialist that offers custom synthesis is brought in. These contracts are carried out under strict confidentiality agreements and delivery deadlines. The customer usually defines the quantity and the quality that they need and may also provide a recipe or a process, or alternatively a new synthetic route to be designed to make it. Custom synthesis can be as low as a few milligrams, or as high as 10 kilos or more. Above that scale, it’s normally called contract manufacturing.
There are several advantages of a pharmaceutical company contracting an external supplier for a compound. Some may have some expertise in a particular area of chemistry or some facilities that the pharma company may not have. A big pharma company has its own synthesis team in-house; which are better at doing research and development work. Such pharma companies prioritise what’s best for their own chemists. Custom synthesis houses can be less expensive. The rates of pay at pharma companies are considerably higher than the supplier base. When they do not have the in-house resources to do the chemistry during high demand, they can look at external suppliers to help them. There are also a number of virtual pharma companies and small bio-techs who don’t have their own chemistry facilities, and it’s a necessity for them to get companies to make products for them.
The main challenges occur during the scaling up production from grams to kilos. Very often, a process or a recipe from either the company or from the literature has been done at a relatively small scale, and by a medicinal chemist who has been making the compound for research efforts. The chemistry is not important, than getting the molecule for the right biological effect. Expensive reagents or a convoluted route are used to give the product in the end. So it’s not possible to scale up a medicinal chemist’s process, because of safety or reactivity issues. Many “all-on-board” reactions, with all agents in a pot, are exothermic whose heat generated is usually managed on that small scale. But on a large scale, the large amount of heat can be very dangerous. The chemistry has to be studied to see if that can be scaled up to achieve a safe, robust and repeatable process.
Speed and reliability are two important expectations from providers of custom synthesis, along with flexibility and strong technical ability. While scaling up, problems can be overcome only by good chemists and scientists.