FDA gives update on pediatric drug shortages and approvals

Pediatric drug shortages are not likely to disappear, but the U.S. Food and Drug Administration (FDA) is pushing to limit the clinical impact of shortages, particularly of pediatric agents. The 2020 Coronavirus Aid, Relief, and Economic Security Act (CARES) allows the agency to require drug manufacturers to create risk mitigation plans for all life-saving drugs and active pharmaceutical agents. Combined with existing drug shortage oversight programs, the agency prevented 199 drug shortages in 2020.

“There is always a sense of urgency when it comes to drug shortages,” said Cmdr. Hyun Son, PharmD, FDA Drug Shortage Staff Senior Program Management Officer, during the FDA: Pediatric Update on Monday, November 14, at ACR Convergence. “Ultimately, we want to ensure a safe, reliable drug supply.”

The session is available for on-demand viewing for registered ACR Convergence participants through October 31, 2023, on the virtual meeting website.

U.S. providers recently have been hit with 43 new drug shortages, Dr. Son said. The agency can, and does, require advance notification of manufacturing and supply disruptions or delays, product discontinuations, and manufacturing changes to help mitigate disruptions.

“We cannot require a company to make a drug or to make more of a product,” she said. “Nor can we say how much of a drug is distributed and which purchases will be given priority. We can advise, assist, and expedite inspections and reviews, but the onus lies on the manufacturer to fix the problem.”

Triamcinolone hexacetonide for injection remained in short supply at the time of ACR Convergence, Dr. Son reported. The FDA exercised its regulatory discretion to allow product import to address the shortage and was working with the manufacturer on a long-term solution.

Tocilizumab, which had fallen into shortage due to increased demand during the COVID-19 pandemic, is generally available with increased manufacturing capacity.

The FDA has an online list of current drug shortages that is updated daily, and providers or institutions encountering problems can contact the agency by email at [email protected].

The agency has also been moving pediatric rheumatology drug approvals. Three new approvals passed review as of the third quarter of 2022, reported Amit Golding, MD, PhD, Medical Officer, FDA Division of Rheumatology and Transplant Medicine, including belimumab IV for pediatric lupus nephritis (LN), ustekinumab for juvenile psoriatic arthritis (JPsA), and secukinumab for both JPsA and enthesitis-related arthritis (ERA).

The agency has also approved seven biosimilars to adalimumab and two biosimilars for etanercept for juvenile idiopathic arthritis in the past year.

“Pediatric approvals range along a continuum of disease/response similarity, from no similarities between adult and pediatric conditions to significant overlap and no known significant differences between the adult and pediatric conditions,” Dr. Golding said. “For drugs with a large degree of overlap between adult and pediatric conditions, we can often use bridging biomarkers, pharmacokinetic (PK) exposure, and extrapolation from established efficacy in adults and existing pediatric data.”

The belimumab approval for pediatric LN was based largely on PK exposure and extrapolation from adult data, as well as an earlier pediatric systemic lupus erythematosus trial. Dosing is the same in children as in adults (10 mg/kg), with a similar safety profile in both populations.

The ustekinumab approval for JPsA was similarly based on PK exposure and extrapolation from adult data, bolstered by completed studies in pediatric plaque psoriasis.

By contrast, secukinumab was approved on a randomized withdrawal study in patients 2–18 years of age with time to flare as the primary endpoint, Dr. Golding said. Secukinumab reduced the rate of flare by 80 percent in JPsA and 53 percent in ERA.

Biosimilar approvals are based on the familiar basis of analytical data, animal studies, pharmacology, and clinical studies to confirm a highly similar structure and function with the reference product and similar efficacy and safety. One of the approved biosimilars to adalimumab, adalimumab-adbm, is fully interchangeable with the reference product.

Dr. Golding noted that the FDA had approved 38 biosimilar products as of September 2022.