Issue link: https://www.e-digitaleditions.com/i/1420709
Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 9 chemistry in the plant that isn't well defined can be challenging. There are a number of components that need to be navigated, and you work to make sure the customer can maximize their opportunity at launch, helping patients who need them. Once the process is validated, manufacturing can begin on a commercial scale." Chris Seekamp, director of CMC, Sterling Pharma Solutions, agrees scale-up is one of the biggest chal- lenges, particularly working through scale-up issues that weren't originally observed or well-defined in the laboratory evaluation and/or development. "When such scale-up issues arise, the develop- ment teams need to mobilize quickly to determine the best path forward to maintain safety, integrity, strength, purity, and quality (SISPQ) of the prod- uct and also minimize any impact on the delivery schedule," Seekamp continues. In tandem, for commercial manufacturing, a con- siderable challenge—according to Seekamp—is re- ceiving estimated forecast quantities from customers, and then adjusting the manufacturing schedules as the forecast becomes a binding delivery. Trends in API manufacturing "Over the past several years we've seen trends toward more complex products and presentations along with an increased focus on intellectual property at an ear- lier stage in development," says Grabowski. "We've also seen increased interest in orphan drugs to treat rare diseases, which require speed to market." Bernt Dietmar Schober, senior business manager, API, pharma services, Thermo Fisher Scientific and Seekamp also say that rare diseases are (and will be) a focus area in the realm of API manufacturing. "Aside from numerous specific cancer targets, 'unmet needs' are another area of high activity. These mostly focus on rare diseases, with patient numbers in the hundreds or thousands worldwide. These indications usually allow for fast approval, as there is no medication in place yet," says Schober. "Additionally, we still see little demand for work on tropical diseases, with only a few non-profit orga- nizations working on such. These include the Bill & Melinda Gates Foundation and the Drugs for Neglected Diseases Initiative." Seekamp adds that the industry is trending towa rd h ig h ly-potent compou nd s t hat a re typically (but not always) associated with an orphan drug indication. "Highly potent APIs (HPAPIs) present unique challenges to a contract development and manu- facturing organization (CDMO) when being as- sessed, including the containment strategy that must be adopted; at what point in the synthesis the molecule becomes highly potent; and whether the HPAPI is also classed as a DEA controlled sub- stance," says Seekamp. Stanek raises another point, which relates to the challenges for generic-drug producers to sustain revenue. "As more molecules with lower volume demand are developed, it becomes increasingly difficult for generic producers to make money on 'second generation processes,'" says Stanek. "Medications become more specific based on improved under- standing of the biological processes in the body. A 2021 report by Market Research Future estimates that the small-molecule API market will reach US$279,697.1 million by 2027.