Drug shortages can occur for many reasons, including manufacturing and quality problems, production delays, and product discontinuations. Manufacturers provide FDA with information related to potential drug shortages, and the agency works closely with them to prevent or reduce the impact of shortages.
In this CDER Conversation Emily Thakur, CDR, United States Public Health Service, Team Leader for CDER’s Drug Shortage Staff (DSS), talks about recent drug supply challenges, shares new FDA guidance, and offers solutions to mitigate drug shortages.
What are the main causes of drug shortages?
There are many contributing factors. Manufacturing quality issues are the major reason for drug shortages. However, there are other reasons, such as manufacturing production delays. For example, companies have experienced lags in receiving raw materials and components from suppliers. Discontinuations of drug products are another factor contributing to shortages. FDA can't require a firm to keep making a drug it wants to discontinue. Sometimes companies discontinue older drugs in favor of newer, more profitable ones.
For example, consider older, sterile injectable drugs, such as Total Parental Nutrition products. There are few firms making them, and a limited number of production lines. In addition, suppliers are also limited in the amount of components they can make due to capacity constraints at their facilities. This small number of manufacturers and limited production capacity, combined with the long lead times and complexity of the manufacturing process, make these drugs vulnerable to shortage. When one company has a problem or discontinues the drug, it is difficult for the remaining firms to increase production quickly and a shortage can occur.
How does CDER help manufacturers rectify or avoid drug supply and shortage situations?
FDA takes great efforts, within its legal authority, to address and prevent drug shortages and supply issues. CDER uses a variety of tools to monitor the supply chain. CDER does not manufacture drugs and cannot require a pharmaceutical company to make a drug, make more of a drug, or change the distribution of a drug. But we can help encourage companies to do so. For example, due to the COVID-19 pandemic, DSS asked manufacturers to evaluate their entire supply chain, including active pharmaceutical ingredients and finished dose forms.
In a very recent example, we have been closely monitoring the ibuprofen and acetaminophen oral suspension supplies, which have experienced increased demand since the fall of 2022 due to increases in respiratory illnesses. We are working closely with the manufacturers on their efforts to further increase supply in response to the increased demand. In January 2023, we issued guidance to help increase supply of ibuprofen oral suspension products in hospitals and health systems.
Do drug manufacturers have requirements regarding working with CDER to reduce or avoid drug shortages?
It is the drug manufacturers’ responsibility to provide FDA with certain information related to potential supply disruptions, and we work closely with manufacturers to prevent or reduce the impact of shortages that may result.
The Coronavirus Aid, Relief, and Economic Security Act, or CARES Act, included authorities intended to enhance FDA’s ability to identify, prevent, and mitigate possible shortages of drugs by, among other things, enhancing our visibility into the drug and medical product supply chains.
The specific authorities to enhance FDA’s ability to identify, prevent, and mitigate drug shortages include notifying FDA of permanent discontinuances and interruptions in manufacturing of Active Pharmaceutical Ingredients (APIs); creating risk management plans for establishments in which certain drugs are manufactured; and reporting the amount of listed drugs and biological products manufactured.
Recently there seem to be many drug shortages and drug supply issues. Is this the case and if so, why?
Drug shortages aren’t uncommon. However, the triple threat of COVID-19, respiratory syncytial virus, and influenza is beyond what anyone could have predicted. COVID-19 has impacted labor issues as well, though that was more of a concern at the height of the pandemic. Supply issues are also generally more common in winter — we’ve seen seasonal problems for more than a decade. Although the majority of shortages are caused by manufacturing issues, we have also seen some shortages due to increases in demand. Manufacturers are required to notify FDA of permanent discontinuances and certain interruptions in manufacturing, but not necessarily when they are seeing an increase in demand. That gap in knowledge can sometimes lead to shortages that the agency can’t address preventatively. But whether it’s the recent triple threat, increases in demand, or another issue, our team’s strategy is the same: we work closely with drug manufacturers to communicate issues and to help restore availability.
When and how are drugs added to the drug shortage list?
Since the enactment of the Food and Drug Administration Safety and Innovation Act in 2012, drug manufacturers have been required to notify FDA of changes in the production of certain finished drugs that may, in turn, help the agency in its efforts to prevent and mitigate shortages. When DSS confirms a drug shortage exists, we post this information on the Drug Shortages website. We update the drug shortage list daily with new and resolved shortages, as well as additional information we receive from suppliers on their manufacturing capacity.
Is there a way to resolve drug shortage and supply issues? Can you offer any solutions?
Our team responds to potential drug shortages by taking actions to address their underlying causes and to enhance product availability. We determine how best to address each shortage situation based on its cause and the public health risk associated with the shortage.
The agency also works with other firms making the drugs in shortage to help them ramp up production if they are willing and able to do so. Often, they need new production lines or new raw material sources approved to help increase supplies. We expedite review of these to help resolve shortages of medically necessary drugs. We can't require the other firms to increase production, but we do all we can, within our authority, to mitigate shortages, ideally before they occur.