COVID convalescent plasma guidance gets EUA updates

Guidance for industry on the use of convalescent plasma for patients with COVID-19 has been updated to reflect the 23 August Emergency Use Authorization (EUA) for the investigational product. The guidance clarifies which pathways are available for use of COVID-19 convalescent plasma and announces a period of enforcement discretion for transition to collection requirements outlined in the EUA.
 
Updates to the US Food and Drug Administration (FDA) guidance account for the addition of the EUA pathway for use of investigational convalescent plasma to the original Investigational New Drug (IND) pathway that was delineated the April 2020 version of the guidance and updated the next month. (RELATED: FDA updates guidance on investigational use of convalescent plasma for COVID-19, Regulatory Focus 04 May 2020)
 
“Because convalescent plasma for the treatment of COVID-19 has not yet been approved for use by FDA, it is regulated as an investigational product. As such, its administration must be under the EUA or an IND,” noted FDA in announcing the guidance updates.
 
If convalescent plasma use is sought under the EUA pathway, its use must be consistent with and not exceed terms set out In the Letter of Authorization issued to the Department of Health and Human Services. The scope of authorization for convalescent plasma use is for hospitalized patients with COVID-19; reporting to FDA is not required for use under the EUA pathway, though records must be maintained and any adverse reactions thoroughly investigated. Fatalities related to convalescent plasma use under the EUA must be reported to FDA.
 
Additional study is needed despite the issuance of the EUA for convalescent plasma, said FDA, observing that “adequate and well-controlled randomized trials remain necessary for a definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the optimal product attributes and appropriate patient populations for its use.”
 
Accordingly, says the guidance, “The EUA is not intended to replace clinical trials that are critically important for the definitive demonstration of safety and efficacy of investigational convalescent plasma.” Clinical trials of convalescent plasma that are already underway should not be amended based on the EUA, and investigators wishing to initiate new trials should continue to submit requests to FDA for investigational use of convalescent plasma via the traditional IND pathway. (RELATED: Lawmakers, experts raise questions after convalescent plasma EUA, Regulatory Focus 25 August 2020)
 
The expanded access pathway for convalescent plasma continues to be open in theory; single-patient INDs may be submitted by patients requesting access for patients with serious or life-threatening COVID-19. However, the EUA will largely supplant this mechanism, according to the guidance: “Given that the intended use of COVID-19 convalescent plasma under the EUA is for treatment of hospitalized COVID-19 patients, FDA expects few requests for single patient INDs.”
 
The Letter of Authorization detailing requirements for plasma administration under the EUA also sets conditions for collection of COVID-19 convalescent plasma for use via EUA, including donor eligibility, testing methods for SARS-CoV2 antibodies, and labeling requirements. In particular, the EUA requires that plasma donations be tested for antibodies using the Ortho VITROS SARS-CoV-2 IgG test to determine pre-release suitability during manufacturing. This test also determines whether plasma qualifies as high- or low-titer convalescent plasma.
 
The guidance also lays out parallel collection conditions for convalescent plasma collection under an IND; the Ortho VITROS IgG test is not required under these collection requirements.
 
Many establishments have convalescent plasma in inventory that was collected under INDs prior to the issuance of the EUA, and many institutions are continuing to collect investigational convalescent plasma while they shift to the EUA-specific collection requirements, said FDA in delineating its thinking about enforcement in the guidance.
 
To allow time for transition to the new manufacturing requirements, FDA announced a period of enforcement discretion in the guidance. The updated guidance clarifies that FDA intends to exercise “temporary enforcement discretion regarding the IND requirements for the use of this product when blood establishments, hospitals, and health care providers collect plasma that does not meet the Conditions of Authorization of the EUA.”
 
The 90-day enforcement discretion period will apply for cases where the plasma is intended for hospitalized COVID-19 patients, informed consent has been obtained, the plasma is collected by registered blood establishments from eligible donors, and the label includes the statement “Caution: New Drug – Limited by Federal (or United States) law to investigational use.”
 
FDA