On May 31, 2018, the FDA Commissioner Scott Gottlieb, M.D., issued a statement regarding the FDA’s work to mitigate shortages of intravenous drugs, shorten supply disruptions, and better predict vulnerabilities.
While the causes of drug shortages vary, most shortages are due to disruptions in supply chain availability of actively marketed products. Among these interruptions, manufacturing and quality issues are the leading causes of drug shortages. This includes outdated equipment in need of repair or replacement, unexpected issues with a product’s composition, and a manufacturer’s inability to maintain facility and product quality. The availability of raw materials can also be a key factor in creating supply disruptions. A disruption from one supplier of raw materials can affect production for many drug makers who all depend on that one source of raw material. Companies that supply raw materials can also be subject to quality problems, leading to shortages.
Only two percent of shortages are a result of product discontinuation. For example, when companies that make competing products merge, and discontinue one of the competing products, this can cause a shortage. Manufacturers often make production decisions based on business considerations, such as a product’s profitability, manufacturing costs, distribution quotas, and patent life. Historically, many drugs in short supply have been low-profit generic medications, for which the investment needed to ensure continued production can be less than that for higher profit products.
Even in the absence of any production issues and decisions, there are other issues that can precipitate a shortage. For example, an unforeseen increase in clinical demand, changes in clinical practice guidelines, or even FDA approval of a new indication for an existing drug, can all lead to an unexpected surge in demand for a particular medicine. The increased demand can, in turn, lead to a shortage of that specific drug.
“Given these challenges, the FDA is focused on doing all we can to mitigate existing shortages, and prevent them from occurring,” said Dr. Gottlieb. “While we help avert and minimize shortages in many ways, the FDA can have the best impact by working more closely with sponsors to help prevent shortages before they occur. This starts with the FDA knowing about potential supply disruption well in advance of an actual shortage.”
The Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) generally requires manufacturers to notify the FDA of any disruptions, such as manufacturing changes, production or shipping delays, and product discontinuations likely to affect their supply of prescription drugs for serious illnesses. This vital information allows the FDA to execute other actions within its authority to help avert impending shortages or lessen their impact.
Manufacturers abruptly discontinue, limit, or delay production under circumstances that FDASIA does not require advance notice to the FDA. Manufacturers notify the FDA of potential supply disruptions, but fail to provide enough details to allow the FDA to make the fullest use of its resources to address the shortage. To address these challenges and opportunities, the FDA is exploring additional ways to encourage companies to voluntarily share more timely information about potential supply disruptions.
The FDA’s ability to help resolve shortages also relies on industry seeking approval for drugs currently in short supply. When that opportunity arises, the FDA prioritizes these circumstances. For example, if a new production facility or supplier is needed, the FDA has the regulatory authority to expedite facility inspections and drug application assessments so that the facility can become operational as soon as possible. The FDA can also expedite review of a new or generic drug application that, if approved, may serve as an alternative therapy to a product facing a shortage.
Although the FDA cannot mandate submission of applications for products in short supply, the FDA does alert other manufacturers of similar or alternative products to consider ramping up production to meet an anticipated increased demand for their product. In cases where alternative manufacturing is not available in the U.S., or the manufacturers of U.S.-marketed products are not able to expand production, the FDA may explore importation of a product from a foreign manufacturing source until the shortage is resolved.
The FDA has implemented an emerging technology program and established an emerging technology team to engage with companies about new production technologies that could, in the long run, prevent drug shortages caused by product quality and manufacturing problems. One such technology is continuous manufacturing (CM), a faster manufacturing process that eliminates breaks between steps and reduces opportunities for human errors during the stops and starts in the traditional batch manufacturing process. As with any new technology, implementing CM presents challenges, such as the initial cost of investing in new equipment. The FDA is taking steps to reduce the cost and uncertainty of adopting CM as an important, long-term solution to improve manufacturing reliability.
“Shortages are an inevitable consequence of an imperfect system,” said Dr. Gottlieb. “With better planning, we can minimize shortages throughout the supply chain. But, in the near term, we won’t be able to fully eliminate the possibility that new shortages will arise. Meaningfully impacting the structures and market challenges that can give rise to shortages will require more coordination among public and private stakeholders.”
“We’re evaluating our current authorities to see what more we can do to better mitigate and prevent shortages, including receiving additional, key information from industry when they notify the agency about a possible shortage and identifying all establishments where manufacturing is performed associated with listed drugs and the type of operation performed at each such establishment. It’s essential that we evaluate what additional steps we can take to reduce the incidence and impact of shortages.”
See the FDA Announcement
See also Medical Law Perspectives Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication
See also Medical Law Perspectives Report: Prescription Painkillers: Risks for Patients, Pharmacists, and Physicians