FDA Highlights Quality, Cost Issues in Campaign to Reduce Drug Shortages

Pharmaceutical manufacturers that can ensure a reliable supply of high-quality therapies should be able to command higher prices needed to maintain modern production systems able to avoid drug shortages, according to an FDA expert panel. Drug quality issues account for nearly two-thirds of recent shortage situations, which usually involve low-priced, low-profit sterile injectables that companies would rather abandon than finance the long-term upgrades needed to meet standards. 

This is the main conclusion of a comprehensive FDA report by an inter-agency task force on ways to address the financial, manufacturing, and policy issues underlying short supplies of important prescription medicines in the United States. Ongoing shortages of common, but critical, therapies such as epinephrine and widely used cancer drugs, continue to generate outrage on Capitol Hill and from the public.

Unfortunately, earlier efforts by the Center for Drug Evaluation and Research (CDER) to encourage a greater industry focus on quality and reliability in drug manufacturing met strong opposition. Several years ago, CDER officials proposed that manufacturers assess a series of performance measures defined by an FDA Quality metrics program. The idea then, as now, was that firms could command higher prices for drugs able to document high quality achievement. Even efforts to further the initiative through voluntary programs had little success, as manufacturers objected that FDA rating of production operations and quality programs would be arbitrary, costly, and unlikely to provide useful information to inform drug production and sales.

Now the new drug shortages report revives the call for a rating system to help drug purchasers, hospital buying groups, and consumers identify quality products that warrant higher prices. The analysis documents that drug shortages arise most often from quality production problems involving low-priced sterile products, often made by just one producer. 

In unveiling the report, FDA Acting Commissioner Ned Sharpless and CDER Director Janet Woodcock highlighted the call for a system to measure and rate a facility’s “quality management maturity”that informs the public about its commitment to reliable quality production, instead of just meeting the basic standards set by current good manufacturing practices (cGMPs).

Manufacturers should “sell quality-not just medicine,” Woodcock stated in an earlier FDA “voices” posting. She maintains that a firm’s ability to reliably make a product in sufficient quantities and with sufficient speed to “ensure that supply consistently meets demand over sustained periods of time” should be a strong selling point-something that now is not rewarded due to limited quality product information for purchasers. The team of economists and scientists preparing the report found that of 163 drugs that first went into shortage between 2013 and 2017, 62% of supply disruptions were associated with manufacturing or product quality problems. Only a few had problems due to increased demand or natural disasters. 

Penalties and risk plans

In addition to detailing the harms of drug shortages and need for more reliable solutions, the task force proposes some specific actions to prevent and address shortages, such as permitting longer expiration dates where justified. Legislation should increase penalties on firms failing to provide timely and adequate notification of a likely interruption in production. Here FDA will help with additional guidance that spells out more clearly requirements for manufacturers to notify FDA of expected production interruptions or discontinuance. 

Congress also should authorize FDA to require application holders of certain drugs to conduct periodic risk assessments to identify vulnerability in their manufacturing supply chains and plans to mitigate such risks. New guidance will outline how firms should develop and maintain such risk management plans. 

Manufacturers would be more likely to invest in modernizing facilities and improving formulations if regulatory approval of such post approval changes was faster and more efficient. To this end FDA supports efforts by the International Council for Harmonization (ICH) to finalize a new guideline (Q12) to harmonize procedures governing product lifecycle management. The new standard aims to simplify and support a more efficient global system for regulating manufacturing changes to approved products, a complex process that is often extremely costly and time-consuming for a pharmaceutical company to modernize or alter a production facility that serves multiple markets.