COVID-19 convalescent plasma safety and efficacy analysis for biologics license application approval

COVID-19 convalescent plasma with high anti-SARS-CoV-2 antibody levels transfused within 6 months from donor collection was formally approved by the Food and Drug Administration in December 2024 for COVID-19 treatment in immunocompromised patients. Here we summarize the safety and efficacy data submitted for the Biologics License Application. Safety evaluation in over 100,000 individuals in the expanded access program and 24,000 in randomized controlled trials, showed no serious adverse event increases. Robust randomized controlled trials established efficacy in four distinct disease stages: outpatient, inpatient, newly mechanically ventilated, and in those immunocompromised to prevent acute disease progression or eliminate persistent viral carriage. Pharmacokinetics revealed a three-liter distribution volume with viral specific antibody effective dose near 2–50 mg. Major SARS-CoV-2 antibody-mediated antiviral actions included direct neutralization by viral-binding interference to cell receptors and fragment-crystallizable mediated antiviral effects that reduce virions. Virus neutralization correlated with high anti-Spike antibody levels and antibody levels in the top donor plasma deciles retains therapeutic neutralization against future variants. With pandemic progression, the COVID-19 convalescent plasma safety and efficacy evidence quality increased. Ultimate regulatory approval required robust randomized control efficacy data. Future infectious disease outbreaks require randomized controlled trials in the convalescent plasma roadmap.