FDA Announces Ground Rules for Investigation and Use of COVID-19 Convalescent Plasma Therapy

Arent Fox continues to monitor the FDA activities and scientific reports on COVID-19 and the novel coronavirus.

On March 24, FDA announced that it would allow the use of convalescent plasma from recently recovered COVID-19 patients in the following situations:

  • For investigators wishing to study the safety and efficacy of convalescent plasma in clinical trials via the traditional IND regulatory pathway.
  • For treatment by a licensed physician of an individual patient with serious or life-threatening COVID-19 infections via a single-patient emergency IND (eIND), upon FDA authorization following an application using Form 3926. (This does not cover prophylactic treatment.)
  • For highly time-sensitive emergency treatment of an individual patient with FDA’s verbal authorization alone, but with a Form 3926 application to follow within 15 working days.

FDA has established conditions that both donors and recipients must meet in order to participate in the convalescent plasma program. For example, would-be donors must have complete resolution of COVID-19 symptoms at least 14 days prior to donation, with negative test results and adequate neutralizing antibody titers (if the latter test is available). Would-be recipients must be suffering from severe or immediately life-threatening, laboratory-confirmed COVID-19, and must provide informed consent.

FDA is working with NIH, CDC, and other agencies to develop master protocols for investigators, with the aim of coordinating collection and use of convalescent plasma.

Convalescent plasma is prepared from the donated blood of individuals who have been infected with, and have subsequently completely recovered from, a viral disease, i.e., they are at a convalescent stage. At this point, their blood contains antibodies to the virus. If the plasma is then administered to another individual either at risk from, or actually suffering from, the same viral disease, the antibodies present in the plasma may provide an immediate protection from, or treatment for, that disease. This is in contrast to a vaccine, which induces an immune response that gradually leads to a build-up of antibodies against a virus over days or even weeks.

Convalescent plasma (or serum) therapy has been in use since at least the early twentieth century and was even used during the 1918 influenza pandemic, although it has not been shown to be effective against every viral disease studied. More recently, it was used during the 2003 SARS epidemic, the 2009-2010 H1N1 influenza epidemic, and the 2013 Ebola epidemic, when it was applied (in combination with an experimental drug) to successfully treat two infected individuals who had been repatriated to the US. This work has been summarized in a recent key paper in the Journal of Clinical Investigation by Casadevall and Pirofski.

Although these authors note that the use of the therapy tends to be more effective when used prophylactically rather than for treatment of a disease, at this point in the COVID-19 pandemic it is probably of greater importance to use it primarily for treatment, since initially it will be in short supply and the disease has a significant mortality rate – hence FDA’s current focus.

The journal Nature has just reported in its online newsletter that, as a result of FDA’s decision to allow use of convalescent plasma therapy, at least two hospitals in New York City – Mount Sinai and Albert Einstein College of Medicine – hope to start therapy as early as the week of March 30. It also reports that researchers have submitted to FDA three protocols for placebo-controlled trials that would take place in association with Johns Hopkins, the Mayo Clinic, and Washington University in St. Louis.


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