By Rose Pagano and Suzanne M. Sensabaugh, MS, MBA
In August, the FDA issued an Emergency Use Authorization (EUA) for COVID-19 convalescent plasma for the treatment of hospitalized COVID-19 patients. Since then, the FDA has released a revised EUA. The COVID-19 convalescent plasma may be used under an EUA associated with the proper authorization or under an investigational new drug application (IND). Recently, the FDA released the “Investigational COVID-19 Convalescent Plasma” guidance. This new guidance defines COVID-19 convalescent plasma as a convalescent plasma authorized under the EUA. Specifically, COVID-19 convalescent plasma is human plasma collected from individuals whose plasma contains anti-SARS-CoV-2 antibodies and those individuals must meet all donor eligibility requirements. Additionally, “investigational convalescent plasma” means convalescent plasma that does not meet all the requirements of the EUA and is being used as an IND. Ultimately, this new document is meant to provide clarity to the public on current legal requirements, and this policy will remain in effect for the duration of the public health emergency related to COVID-19 declared by HHS.
Currently, the FDA does not collect or provide convalescent plasma. Healthcare providers or acute care facilities should get convalescent plasma from an FDA-registered or licensed blood establishment. There are multiple pathways to study the use of convalescent plasma. One potential avenue is the emergency use authorization. For this option, healthcare providers administering COVID-19 convalescent plasma under the EUA do not have to report its use to the FDA. These providers should use the Fact Sheet for Health Care Providers for information on the intended use and possible risks and benefits of COVID-19 convalescent plasma. It is important for the providers to maintain records and execute an investigation of adverse reactions after transfusion of COVID-19 convalescent plasma, and report fatalities to FDA. See the guidance “Notifying FDA of Fatalities Related to Blood Collection or Transfusion” for recommendations on reporting fatalities related to blood transfusion to FDA.
Another pathway for administering and studying the use of convalescent plasma in clinical trials. The EUA is not meant to replace clinical trials that are necessary for the definitive demonstration of safety and efficacy of convalescent plasma. Healthcare providers are encouraged to enroll patients in clinical trials of investigational convalescent plasma to help better understand the effectiveness of convalescent plasma for the treatment of COVID-19. To explore convalescent plasma in a clinical trial, investigators should submit requests to FDA for investigational use under the traditional IND regulatory pathway. During the COVID-19 pandemic, INDs may be submitted via email to CBERDCC_eMailSub@fda.hhs.gov. Also, an IND application for expanded access is another alternative for use of investigational convalescent plasma for patients with COVID-19 who cannot enroll in randomized clinical trials.
Additionally, due to the COVID-19 public health emergency, the FDA is continuing to allow access to investigational convalescent plasma through the process of a physician requesting a single patient IND for an individual patient with serious or life-threatening COVID-19 under 21 CFR 312.310. This allows for the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization, if the applicable regulatory criteria are met.
Overall, blood establishments collecting authorized COVID-19 convalescent plasma need to comply with the Condition for Authorization in the EUA. According to the EUA, authorized COVID-19 convalescent plasma must be gathered by registered blood establishments from donors in the US. The plasma donations must be tested by these blood establishments for the anti-SARS-CoV2 antibodies and appropriately labeled. For an IND, the FDA must receive information regarding the investigational drug chemistry, manufacturing, and controls to ensure correct identification, quality, purity, and strength of the drug. INDs for the use of investigational convalescent plasma must also show the plasma has SARS-CoV-2 neutralizing antibody titers, if possible. Healthcare providers should include information in the IND submission from an FDA-registered blood establishment that follows donor eligibility criteria, donor qualifications, anti-SARS-CoV2 antibodies testing, labeling, and recordkeeping. The FDA will continue to provide updated guidance related to COVID-19.
Suzanne is the President and Principal Consultant of HartmannWillner LLC. She is an FDA regulatory affairs consultant who assists companies in advancing biologics, biosimilars, and biologic/device combination products through the FDA.
She formed HartmannWillner in 2009 as a regulatory affairs consultant. Since then, Suzanne has:
- Assisted in the development of over 130 biologics, biosimilars, and biologic/device combination products
- Conducted over 30 FDA GMP audits, including preapproval inspections (PAI), which allowed for FDA approval
- Provided GMP compliance consulting to successfully address Form FDA 483 observations and Warning Letters
- Prepared expert witness opinions and testimony in the areas of FDA regulatory affairs and GMP compliance
- Wrote and reviewed hundreds of original INDs and BLAs and amendments and supplements