{"doi":"10.1111/trf.16751","title":"Regulatory challenges of convalescent plasma collection during the evolving stages of <scp>COVID</scp>‐19 pandemic in the <scp>United States</scp>","abstract":"December 2019 marked a watershed for global health when a large number of patients presenting with severe respiratory symptoms were hospitalized in Wuhan, China. Some patients (about 5%) developed acute respiratory distress syndrome and had a rapidly deteriorating clinical course, in spite of intensive care and ventilatory support.1, 2 Nasopharyngeal swabs revealed a novel coronavirus that was different in epidemiological, clinical, and molecular features from coronaviruses that caused outbreaks of severe acute respiratory syndrome (SARS-1) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012.2 Within just a few weeks after December 2019, cases were found in increasing numbers in European countries and the United States. On February 4, 2020, coronavirus disease 2019 (COVID-19) was declared a public health emergency in the United States by Health and Human Services (HHS). By February 24, 2020, more than 80,000 confirmed cases and more than 2700 deaths had been reported affecting at least 37 countries.3 On March 11, 2020, it was characterized as a pandemic by the World Health Organization (WHO). Since there were no evidence-based therapeutic and preventive options available,4 clinical trials of existing therapeutics including remdesivir, chloroquine, hydroxychloroquine, lopinavir, and ritonavir to treat COVID-19 were emergently started.5 COVID-19 convalescent plasma (CCP) was considered a viable and possibly useful therapeutic based upon the past treatment of respiratory viral diseases.6 Hence, the trials were started, and the initial case series reports involving a small number of patients were suggestive of a potential benefit.7, 8 Due to historic data regarding the safety and efficacy of convalescent plasma use in other respiratory diseases and new data from preclinical and early clinical studies, FDA began granting requests for emergency single patient investigational new drug (eIND) applications in late March, 2020, and issued guidance for CCP use as an IND in April, 2020.5, 9 FDA sanctioned an alliance between major blood suppliers, the Mayo Clinic, and transfusion services to create the National Expanded Access Treatment Protocol (EAP). The EAP permitted the use of CCP in patients without having to apply for an IND for each patient.10 FDA-licensed blood collection establishments across the United States faced a drastic, emergent challenge and started collecting CCP from qualifying donors on a large scale, as COVID-19 cases continued multiplying.11, 12 Convalescent plasma had been used in viral epidemics of SARS-1, H1N1 influenza virus,13 Ebola14, 15 and MERS with favorable results in some studies, though most published studies were performed on a small number of patients and were nonrandomized. Historically, it was also reported to benefit patients during the influenza pandemic in 19184, 16 and to significantly reduce fatality in patients of Argentine hemorrhagic fever, if used early in the course of disease.17, 18 On April 24, 2020, WHO guidance mentioned lack of enough evidence to guarantee that having antibodies insured immunity against SARS-CoV-2.19 Even though evidence was insufficient, CCP was considered modestly important and one of the only small number of potentially effective treatment options due to its historic use, safety, and lack of alternate options.6, 19 On March 27, 2020, HHS declared that circumstances existed that justified the emergency use of drugs and biological products pursuant to section 564 of the Federal Food, Drug and Cosmetic (FD&C) Act (Figure 1). In April, 2020, FDA issued guidance for CCP collection as an IND,20 and its administration under IND application used three pathways, that is, traditional IND for regulatory clinical trials, using the EAP, or single patient eIND for patients hospitalized with COVID-19.20 In early April, Mayo clinic initiated the EAP under funding from Biomedical Advanced Research and Development Authority (BARDA), whose primary goal was to provide CCP to ","journal":"Transfusion","year":2021,"id":204670,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320681,"name":"Kamille A. West","orcid":"0000-0001-8152-804X","position":1,"is_corresponding":false},{"id":787508,"name":"Kathleen Conry‐Cantilena","orcid":null,"position":2,"is_corresponding":false},{"id":554214,"name":"Valeria De Giorgi","orcid":"0000-0001-5296-8628","position":3,"is_corresponding":false},{"id":773492,"name":"Sajjad Hassan","orcid":"0000-0002-7264-5989","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:51:26.121843Z","pmid":"34778974","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}