Compounders win some flexibility as FDA responds to pandemic-related shortages

Erin McCallister Senior Manager, Health Research Institute, PwC US May 07, 2020

Demand for supportive medicines for the most severe COVID-19 patients has prompted the FDA to relax compounding oversight for some of these drugs. The move is intended to increase supply quickly, but it could also backfire, as looser compounding rules in the past have resulted in safety issues.

Patients with severe cases of COVID-19 can experience acute respiratory distress syndrome (ARDS), which can require ventilation. They can also be at an increased risk of acute kidney injury due to sepsis or multi-organ failure. These resulting side effects have had a spillover effect on the medical products supply chain for supportive care drugs such as sedatives and dialysis fluids.

On April 16, the FDA issued new guidance that outlines a temporary policy for compounding a select set of drugs required for patients hospitalized with severe cases of COVID-19.

The guidance lists 13 drugs that are either in shortage or that hospitals have had trouble accessing because of regional disparities in COVID-19 infection rates or other reasons. The drugs include sedatives such as fentanyl and ketamine, required for intubation, as well as antibiotics such as vancomycin.

Under the policy, the “FDA does not intend to take action against an outsourcing facility for compounding a drug product that is essentially a copy of an approved drug, for using a bulk drug substance that is not on FDA’s 503B Bulks List, or for not meeting CGMP [current good manufacturing practice] requirements with regard to product stability testing and the establishment of an expiration date.”

The compounded drug must be among the 13 included in the guidance, must be provided directly to a hospital that informs the compounding pharmacy that it is treating patients with COVID-19, the substances used to compound the product must be in compliance with the Food, Drug and Cosmetic Act and sourced from facilities registered with the FDA, and they must meet stability testing and expiration date requirements outlined in the guidance.

On April 22, the FDA issued a new guidance on repackaging and combining of propofol drug products for COVID-19 patients who have been sedated and intubated. The drug is on FDA’s shortage list, but pharmacies and outsourcing facilities have access to propofol in different “presentations,” which could be combined or repackaged to meet the demand for the drug. 

The guidance outlines the specific circumstances under which the FDA would permit repackaging of propofol given some of the concerns about the drug’s stability when exposed to oxygen and the potential safety issues that could arise by combining containers of propofol that use different preservatives.

On May 1, the FDA issued an emergency use authorization (EUA) for a continuous renal replacement therapy to address kidney fluid shortages as hospitals in hard-hit areas such as New York City report shrinking supplies of equipment and component medicines

HRI impact analysis

The FDA’s actions to relax some requirements for drug compounding come after the agency has exercised greater authority over the process in the past few years amid safety concerns.

In 2013, the Drug Quality and Security Act established a voluntary category of compounders known as outsourcing facilities that would be subject to current good manufacturing practice (CGMP) requirements and FDA inspection. The law also increased the FDA’s oversight of compounding pharmacies.

The move came after the 2012 outbreak of fungal meningitis from a steroid formulated at a compounding facility in New England that infected 751 people and killed 64. 

Between 2013 and 2015, 55 compounding pharmacies registered with the FDA to comply with the law. According to IBISWorld, there are over 200 compounding facilities in the U.S.

Since 2013, the FDA has increased its efforts to improve manufacturing and compliance at compounding facilities. In April 2019, then-FDA Commissioner Scott Gottlieb outlined additional plans by the agency to create a Compounding Quality Center of Excellence. The center conducts in-person and online trainings for outsourcing staff.

The FDA also issued four guidance documents related to drug compounding from 2019 until the COVID-19 outbreak, including a new draft guidance in January related to CGMP manufacturing.

Read our research

Contact us

Trine K. Tsouderos

HRI Regulatory Center Leader, PwC US

Tel: +1 (312) 241 3824

Crystal Yednak

Senior Manager, Health Research Institute, PwC US

Erin McCallister

Senior Manager, Health Research Institute, PwC US

Follow us