FDA Opens Submissions for COVID-19 IND Applications

On March 24, 2020, the US Food and Drug Administration (FDA) announced that healthcare providers (HCPs) may seek approval to use investigational Coronavirus (COVID-19) convalescent plasma under a single patient emergency investigational new drug (IND) application. Convalescent plasma, which is collected from recovered patients and contains antibodies to SARS-CoV-2, the virus that causes COVID-19, may be effective to treat COVID-19, but has not been the subject of the clinical trials required to support FDA approval.

This announcement, which follows on the heels of FDA announcements intended to facilitate access to ventilators (read more here), diagnostic tests (read more here) and vaccines (read more here) for COVID-19, is notable because it represents the agency’s first effort to expedite access to an investigational drug or biologic for the treatment of COVID-19. In the short term, however, uptake of this option may be limited as access to the diagnostic tests required to confirm donor eligibility continues to be limited.

Eligible Patients

To be eligible to receive convalescent plasma under a single patient emergency use IND, patients must have:

• Laboratory-confirmed COVID-19
• Severe or immediately life-threatening conditions, as defined by FDA for these purposes:
  • “severe” is defined as involving one or more of the following:
    • dyspnea
    • respiratory frequency ≥ 30/min
    • blood oxygen saturation ≤ 93%
    • partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
    • lung infiltrates > 50% within 24 to 48 hours
  • “life-threatening” is defined as involving one or more of the following:
    • respiratory failure
    • septic shock
    • multiple organ dysfunction or failure
• Provided informed consent.

HCPs who need emergency authorization (i.e., a response in less than four hours) may call FDA’s Office of Emergency Operations at 1-866-300-4374 for a verbal authorization and then must submit an expanded access application (Form 3926) to FDA at CBER_eIND_Covid-19@fda.hhs.gov within 15 working days. HCPs who need a response within four to eight hours should complete and submit a Form 3926, which includes (1) a brief clinical history (diagnosis, current therapy, rationale for the request) and (2) a description of where the HCP will obtain the donor plasma.

Eligible Donors

FDA is working with the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) to develop protocols regarding the collection and use of COVID-19 convalescent plasma. Under FDA regulations, COVID-19 convalescent plasma may be collected from recovered individuals only if they are otherwise eligible to donate blood under 21 CFR §§ 630.10 and 630.15 (e.g., the donor must be in good health and free from transfusion-transmitted infections) and the donation is found suitable under 21 CFR § 630.30 (e.g., the blood is tested in accordance with the requirements of 21 CFR § 610.40 and found negative or nonreactive and does not have bacterial contamination).

Additional considerations for donor eligibility include:

• Prior diagnosis of COVID-19, documented by a laboratory test
• Complete resolution of symptoms at least 14 days prior to donation
• Negative results for COVID-19 from at least one nasopharyngeal swab specimen or a molecular diagnostic test for blood
• Defined SARS-CoV-2 neutralizing antibody titers, if testing can be conducted
• Female donors negative for human leukocyte antigen (HLA) antibodies or male donors

Plasma containers must be labeled with “Caution: New Drug–Limited by Federal (or United States) law to investigational use.”