Drug Shortages Continue to Plague FDA, Manufacturers

Jill Wechsler
Washington correspondent
Pharmaceutical Executive

The FDA recently took the unusual step of approving the import of a widely used cancer drug from a Chinese manufacturer in the face of an outcry from physicians and patients over short supplies of vital oncology therapies. Although the regulators have revved up efforts in recent years to better prevent and address drug shortages, serious problems continue to plague drug production and distribution, particularly for a number of generic injectables.

National drug shortages rose in the first quarter of this year, according to the University of Utah Drug Information Service for the American Society of Health-System Pharmacists (ASHP). Many serious shortages involve sterile injectables, such as cisplatin, carboplatin, and methotrexate, which are difficult to obtain quickly from alternative sources. The situation prompted FDA to authorize temporary importation of unapproved cisplatin from Qilu Pharmaceuticals to be distributed in the US by Canadian-based Apotex Corp. FDA Commissioner Robert Califf noted in a social media message that the drug will come from registered facilities and will undergo careful assessment to ensure that the imported drug is safe for patients.

Another example of FDA exercising regulatory flexibility is its decision to permit India manufacturer Intas Pharmaceuticals to export to the US cisplatin and several other medically necessary injectable medicines in short supply, despite citation for multiple manufacturing deficiencies found during recent site inspections. FDA has required the company to provide third-party certification to confirm that products meet quality attributes and are not involved in data integrity violations. With the resumption of FDA plant inspections delayed by the COVID-19 pandemic, particularly with foreign facilities, the agency has uncovered more data and production quality issues, which have led to import restrictions that have limited supplies.

Although manufacturers are required to notify FDA in advance of anticipated production and supply problems, agency officials seek added legislative authority to strengthen reporting requirements for drug and medical device makers, similar to temporary provisions approved during the COVID health emergency. The agency also would like to be able to require industry reports on rising market demand for certain drugs, as occurred during the recent surge in respiratory infections. FDA currently lacks authority to collect this information but is backing proposed changes for inclusion in reauthorization of the Pandemic and All-Hazards Preparedness Act, which hopefully will advance through Congress in the coming months. Some legislators also want to revise the Controlled Substances Act to ensure patient access to ADHD treatment Adderall by better control of supply and diversion.

Manufacturers of new treatments, such as Novo Nordisk’s weight-loss drug Wegovy, can better manage supply by taking steps to lessen demand, such as reducing supplies of a lower starting dose to discourage new patient treatment. Ideally, firms could respond to supply problems by shifting manufacturing lines to increase production of a needed medicine, but often are hampered by limited staff, resources, and ingredients. FDA recommends that companies stockpile backup supplies, but, again, cannot require such action.

Generics squeezed

The broader problem is that shortages of cancer drugs and many widely used sterile injectables are made by generic companies with limited redundancy in production due to very tight margins, as health plans and pharmacy benefit managers push down prices. If a facility inspection uncovers serious quality issues or a company experiences increased costs for materials and operations, that may compel a plant shutdown that can impact the broader supply chain. In remarks at the annual meeting of the Biotechnology Innovation Organization in June, Califf ascribed most drug shortages to generic firms going out of business, either because they fail to invest in quality operations or because they can’t make a profit from the squeeze on prices.

Such concerns were cited in a discussion of supply chain resilience at the Food and Drug Law Institute annual conference in May. A generic drugmaker warned against FDA imposing added costs on industry, such as instituting quality metrics, because generics firms fear that purchasers will not pay more for medicines from facilities that earn high-quality ratings.

FDA described the challenges in coping with these issues in its latest report to Congress on drug shortages for 2022. The update acknowledges still high ongoing shortage situations.