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Convalescent plasma shows promising efficacy in hospitalized patients with COVID-19, and the benefits outweigh the risks, the FDA said in announcing (EUA) for such products on Sunday.

The to the Office of Assistant Secretary for Preparedness and Response within the Department of Health and Human Services. It is not for any particular convalescent plasma product, but rather any such preparation "collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements," according to a .

"Independent experts at the FDA who reviewed the totality of data" including more than a dozen published studies "concluded convalescent plasma is safe and shows promising efficacy, thereby meeting criteria for an emergency use authorization," FDA commissioner Stephen Hahn, MD, said at a press conference on Sunday night.

The agency noted the EUA was based on historical evidence of convalescent plasma in prior outbreaks of respiratory viruses, preclinical evidence, small trials conducted during the outbreak (including some in China), and the ongoing National Expanded Access Protocol (EAP) sponsored by the Mayo Clinic.

The FDA also added that COVID-19 convalescent plasma with "high antibody titer" may be effective in reducing mortality in hospitalized patients, but low antibody titer units may also be used, based on a healthcare provider's discretion. In fact, convalescent plasma is only defined as "human plasma collected ... from individuals whose plasma contains anti-SARS-CoV-2 antibodies" and meet all donor eligibility requirements. Preparations' labels must indicate whether they contain high or low titers.

In its statement, the agency said, "it is reasonable to believe that COVID-19 convalescent plasma may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients."

The agency recommended randomized trials, however, "as COVID-19 convalescent plasma does not yet represent a new standard of care based on the current available evidence."

At the press conference, Hahn noted the Mayo Clinic EAP was supported by the federal government, and has been treating patients with convalescent plasma since April. Over 100,000 COVID-19 patients enrolled, and close to 70,000 patients received treatment.

The tipping point for the agency appeared to be that "optimal" patients who were treated with "convalescent plasma at the highest [antibody] titers" showed "significant clinical benefit" of a 35% improvement in survival, which "clearly meets the criteria published for an EUA," Hahn added.

"That means of 100 people who are sick, 35 [would have] been saved by convalescent plasma," he said.

Data from the trial found patients who received the treatment within 3 days of being diagnosed benefited the most from treatment, Secretary of Health and Human Services (HHS) Alex Azar said. Patients who were under age 80 and not on artificial respiration also benefited.

President Trump hailed the announcement as "truly historic," and said it will "save countless lives."

"Based on the science and the data, the FDA has made the determination that the treatment is safe and very effective," the president said.

The New York Times reported last week that National Institute of Allergy and Infectious Diseases (NIAID) director, Anthony Fauci, MD, and NIH director, Francis Collins, MD, both argued convalescent plasma data from the Mayo Clinic was , namely because the results had not been confirmed in a randomized trial.

On Saturday, , "The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd. Must focus on speed, and saving lives!" He also mentioned Hahn's FDA Twitter handle in the tweet.

But on Sunday, President Trump praised the FDA at the press conference, saying the agency "really stepped up, especially over the last few days." He added, however, that "there are people in the FDA" who wouldn't mind if this process was held up "and that has to do with politics."

Hahn's only allusion to the controversy before was in his opening remarks, when he said the president "asked to cut back red tape at the FDA."

He said research on convalescent plasma will continue, including randomized clinical trials, but the EUA will also enable the agency to meet demand for plasma from "doctors around the country."

It's unclear, though, how much will be available at any given time or whether every eligible patient can have it.

Dosing suggestions include starting with one unit of convalescent plasma of about 200 mL, and adding additional units based on a physician's judgment and patient's response. Patients with impaired cardiac function and heart failure may require either a smaller volume or a longer transfusion time, the agency said.

Plasma may be contraindicated for patients with a history of "severe allergic reactions or anaphylaxis" to plasma transfusion. Side effects include transfusion-transmitted infections, such as HIV, and hepatitis B and C, as well as allergic and anaphylactic reactions.

Risks include antibody-dependent enhancement of infection, where a disease is enhanced in the presence of certain antibodies. For example, the agency said theoretically, "antibodies to one type of coronavirus could enhance infection to another strain." Antibody administration could also attenuate the immune response, and make patients more susceptible to reinfection, the agency noted.

Convalescent plasma safety and effectiveness has not been evaluated in pediatric or pregnant populations, nor in nursing mothers.

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