The Bottlenecks That Slow Manufacturer Response to Increased Demand for Production

Drug shortages remain a difficult to fix issue for the pharma industry and are an issue that can have devastating results. Often times, shortages hit because of an increased demand for the medication, leaving patients waiting for gaps in the supply chain to be filled.

Pharmaceutical Executive spoke with Marc Wagner, an FDA and life sciences attorney at Fox Rothschild, about the manufacturing and regulatory pressures that contribute to drug shortages. According to him, these shortages happen for a variety of reasons and there is single fix.

Instead, there are multiple steps the industry must take to prepare for increases in demand and pipeline disruptions. A major issue is the industry’s dependence on overseas production, which leaves the supply open to global pressures. According to Wagner, a majority of generic drug products are manufactured outside of the US, meaning that these sites may not be unable to pick the slack.

Pharmaceutical Executive: What bottlenecks slow manufacturer response to increased demand for production?
Marc Wagner: There are several bottlenecks contributing to drug shortages. One of the most significant is overseas API dependency and the complexity of the global supply chain.

I like to analogize drug manufacturing to baking a cake. When you bake a cake, you need sugar, flour, eggs, and other ingredients. You mix them together, put the pan in the oven, and your finished product is a cake. Drug manufacturing, while far more complex, follows a similar basic structure. You need starting materials — active pharmaceutical ingredients — which are the equivalent of your sugar, eggs, and flour. You combine those in a highly controlled environment, and the end product is a finished drug.

The critical difference is that drug manufacturers don't have a grocery store down the street where they can procure their active pharmaceutical ingredients. Much of the API used in the United States is sourced overseas, primarily from India and China. Transatlantic shipments take time on their own. It takes time to qualify API suppliers. And in many cases, shipments pass through intermediary countries before reaching their final destination — meaning there are multiple stops along the way before the ingredients needed to manufacture a drug actually arrive where they need to be.

Beyond supply chain complexity, there are significant bottlenecks when manufacturing problems arise and a manufacturer needs to scale up production. If a company needs to modify an existing facility, add a new manufacturing site, or change an API source, there are regulatory requirements that must be met. The manufacturer typically must obtain FDA approval through a prior approval supplement or another supplemental submission to its new drug application. I have seen manufacturing site approvals take as long as three to four years.

Adding new equipment creates additional delays. Any time a production facility installs complex drug manufacturing equipment — whether by adding a new production line or modifying an existing facility — the company must complete qualification and validation, including installation qualification, operational qualification, and performance qualification. Each of these steps takes considerable time before the equipment can be used in commercial drug manufacturing.