CONVALESCENT PLASMA THERAPY FOR COVID-19 PATIENTS: REGULATORY GUIDANCE ON COLLECTION, TESTING, PROCESSING, STORAGE, DISTRIBUTION, AND CLINICAL TRIALS
Keywords:Passive immunization, Transfusion safety, Convalescent plasma, COVID-19, Plasmapheresis
Convalescent plasma can be transfused to patients suffering from the same infection or for preparing immunoglobulin concentrates. Plasma obtained from recovered patients can be a valuable alternative during the COVID-19 pandemic for supporting its treatment within a randomized or case-control clinical trials or observational studies of plasma transfusion and for preparing plasma-derived biological products. WHO Blood Regulators Network highlighted that a systematic approach for collecting convalescent plasma from patients recovered from COVID-19 could provide a useful intervention. Structured clinical trials can be used to assess safety and effectiveness of convalescent plasma. The convalescent plasma therapy is still in the experimental stage and is currently not included in the interim clinical guidelines of WHO. However, an emergency investigational new drug application (eIND) process has been induced to ensure the availability of COVID-19 convalescent plasma to the patients with severe or life-threatening COVID-19 conditions. USFDA is regularly amending its guidance as new results, and best practices are emerging. The write-up provides an overview of convalescent plasma, from a regulatory considerations viewpoint, systematic workflow protocol, and a cross-section of clinical trials underway.
Liang T. Handbook of COVID-19 Prevention and Treatment. Zhejiang: University School of Medicine; 2020. p. 35-6. Available from: https://www.issuu.com/iknowcorp/docs/handbook_of_covid-19_ prevention__english_version.
World Health Organization. Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment During Outbreaks: Interim Guidance for National Health Authorities and Blood Transfusion Services; 2014. Available from: https://www.euro.who.int/__data/ assets/pdf_file/0011/268787/Use-of-Convalescent-Whole-Blood-or-Plasma-Collected-from-Patients-Recovered-from-Ebola-Virus- Disease-for-Transfusion,-as-an-Empirical-Treatment-during- Outbreaks-Eng.pdf.
Griensven JV, Edwards T, de Lamballerie X. Ebola-Tx consortium. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med 2016;374:33-42.
Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, et al. Convalescent plasma: New evidence for an old therapeutic tool? Blood Transfus 2016;14:152-7.
Rajam G, Sampson J, Carlone GM, Ades EW. An augmented passive immune therapy to treat fulminant bacterial infections. Rec Pat Antiinfect Drug Discov 2010;5:157-67.
Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev 2000;13:602-14.
Yadav R, Pathak K, Pathak D, Kumar R. Chemoprophylatic. Ayurvedic, homeopathic and unani approaches for COVID-19 prophylaxis. Pharm Biomed Res 2020;6:341.
Robbiani DF, Gaebler C, Muecksch F, Lorenzi JC, Wang Z, Cho A, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020;584:437-59.
Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. Convalescent plasma in the management of moderate covid-19 in adults in India: Open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020;371:m3939.
COVID-19: What is Convalescent Plasma? Health, The Sciences. 2020. Available from: https://www.science.thewire.in/the-sciences/covid-19- what-is-convalescent-plasma.
Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani A, et al. Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia. Emerg Infect Dis 2016;22:1554-61.
Cheng Y, Wong R, Soo YO. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005;24:44-6.
Devasenapathy N, Ye Z, Loeb M, Fang F, Najafabadi BT, Xiao Y, et al.Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: A systematic review and meta analysis. CMAJ 2020;192:E745-55.
US Food and Drug Administration. Investigational COVID-19 Convalescent Plasma (Guidance for Industry). FDA 2020. Available from: https://www.fda.gov/vaccines-blood-biologics/ investigational-new-drug-ind-or-device-exemption-ide-process-cber/ recommendations-investigational-covid-19-convalescent-plasma.
Joyner M, Wright RS, Fairweather D, Senefeld J, Bruno K, Klassen S, et al. Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. J Clin Invest 2020;130:4791-7.
Joyner M. Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19. 2020. Available from: https://www. uscovidplasma.org/pdf/COVID-19%20Plasma%20EAP.pdf.
Efficacy of Convalescent Plasma Therapy in Severely Sick COVID-19 Patients. Institute of Liver and Biliary Sciences, India 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04346446?id=NCT04346446&draw=2&rank=1&load=cart.
Guide on the Compassionate Use of Convalescent Plasma Therapy for Covid-19. UP-Philippine General Hospital Technical Working Group; 2020. Available from: http://www.isbtweb.org/fileadmin/user_upload/ Deonne_Thaddeus_V_Gauiran_Philippines.pdf.
Guidelines on Clinical Management of COVID-19. Ministry of Health and Family Welfare; Government of India; 2020. Available from: http:// www.mohfw.gov.in/pdf/ClinicalManagementProtocolforCOVID19. pdf. [Last accessed on 2020 Aug 25].
Smid WM, Burnouf T, Epstein J, Kamel H, Sibinga CS, Somuah D, et al. Points to Consider in the Preparation and Transfusion of COVID-19 Convalescent Plasma in low- and Middle-Income Countries; 2020. Available from: http://www.isbtweb.org/fileadmin/ user_upload/FINAL_Points_to_consider_in_the_preparation_of_ COVID_convalescent_plasma_in_LMIC.pdf.
An EU Programme of COVID-19 Convalescent Plasma Collection and Transfusion: Guidance on Collection, Testing, Processing, Storage, Distribution and Monitored Use. European Commission, Directorate-general for Health and Food Safety; 2020. Available from: https:// www.ec.europa.eu/health/sites/health/files/blood_tissues_organs/docs/ guidance_plasma_covid19_en.pdf.
Recommendations for Investigational COVID-19 Convalescent Plasma. USFDA; 2020. Available from: https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma.
Hassan MO, Osman AA, Elbasit HE, Hassan HE, Rufai H, Satti MM, et al. Convalescent plasma as a treatment modality for coronavirus disease 2019 in Sudan. Transfus Apheresis Sci 2020;59:1-5.
Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020;117:9490.
Guidelines on Good Manufacturing Practices for Blood Establishments, TRS 961, 2011. Available from: https://www.who.int/bloodproducts/ publications/GMP_Bloodestablishments.pdf?ua=1.
Epstein J, Burnouf T. Points to Consider in the Preparation and Transfusion of COVID-19 Convalescent Plasma. Working Party of Global Blood Safety, International Society of Blood Transfusion; 2020. Available from: https://www.isbtweb.org/fileadmin/user_upload/ Points_to_consider_in_the_preparation_of_COVID_convalescent_ plasma_-_200331_ISBT_WP_GBS_Final.pdf.
Bloch EM, Bailey JA, Tobian AA. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020;130:2757-65.
Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020;20:398-400.
Li L, Yang R, Wang J, Lv Q, Ren M, Zhao L, et al. Feasibility of a pilot program for COVID-19 convalescent plasma collection in Wuhan, China. Transfusion 2020;60:1773-7.
Pan American Health Organization (PAHO). Regulatory Considerations on Authorization of the Use of Convalescent Plasma (PC) to Address the COVID-19 Emergency; 2020. Available from: https://www.iris. paho.org/handle/10665.2/52036.
World Health Organization. Guidelines on good manufacturing practices for blood establishments. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-fifth Report. Geneva: World Health Organization; 2011. Available from: http://www. who.int/bloodproducts/publications/GMP_Bloodestablishments.pdf.
Roback JD, Guarner J. Convalescent plasma to treat COVID-19: Possibilities and challenges. JAMA 2020;323:1561-2.
Protocol for the Use of Convalescent Plasma for the Treatment COVID-19 Infected Patients; 2020. Available from: http://www. isbtweb.org/fileadmin/user_upload/Qatar.pdf.
Hindwai S. Use of Convalescence Plasma in the Treatment of Patients Infected with Covid-19 Virus Infection (SARS-cov-2); 2020. Available from: https://www.isbtweb.org/fileadmin/user_upload/Convalescence_ Plasma_Protocol_for_COVID19_March_2020.pdf.
World Health Organization. Blood Donor Selection: Guidelines on Assessing Donor Suitability for Blood Donation. Geneva: World Health Organization; 2020. Available from: https://www.apps.who.int/iris/ handle/10665/76724.2012.
Accorsi P, Berti P, Angelis VD, Silvestro GD, Mascaretti L, Ostuni A. Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19. Blood Transfus 2020;18:163-6.
WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020;20:e192-7.
Edwards IR, Aronson JK. Adverse drug reactions: Definitions, diagnosis, and management. Lancet 2000;356:1255-9.
CDSCO. Information on Convalescent Plasma in COVID-19; 2020. Available from: https://www.cdsco.gov.in/opencms/ resources/UploadCDSCOWeb/2018/UploadPublic_NoticesFiles/ MoHFWConvalescentPlasmainCOVIDdraft.pdf.
CLINICAL MANAGEMENT PROTOCOL: COVID-19; 2020. Available from: https://www.mohfw.gov.in/pdf/ ClinicalManagementProtocolforCOVID19dated27062020.pdf.
Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev 1995;9:1-8.
Focosi D, Anderson AO, Tang JW, Tuccori M. Convalescent plasma therapy for COVID-19: State of the art. Clin Microbiol Rev 2020;33:e00072-20.
Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323:1582-9.
Zhang B, Liu S, Tan T, Huang W, Dong Y, Chen L, et al. Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection. Chest 2020;158:e9-13.
CDSCO. A Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease; 2020. Available from: https://www.cdsco.gov.in/opencms/ resources/UploadCDSCOWeb/2018/UploadPublic_NoticesFiles/ amendedClinicalTrialprotocolversion1.4%20byICMRdated2020.pdf.
India’s CDSCO Permits Convalescent Plasma Trial for Covid-19; 2020. Available from: https://www.clinicaltrialsarena.com/news/india-convalescent-plasma.
Convalescent Plasma for COVID-19 Patients Not Responding to Steroids: CDSCO; 2020. Available from: https://www.outlookindia. com/newsscroll/convalescent-plasma-for-covid19-patients-not-responding-to-steroids-cdsco/1883559.
Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics 2020;145:e20200702.
Pathak K, Pathak D, Yadav R, Kumar R. COVID-19: An update on therapeutics and clinical trials. Int J Pharm Sci Drug Res 2020;12:1-9.
U.S. National Library of Medicine. 2020. Available from: https://www. clinicaltrials.gov/ct2/results?cond=convalescent+plasma+therapy+ for+covid+19 &term=& cntry=&state=&city=&dist.
Convalescent Plasma Trial in COVID-19 Patients. Ireland: Royal College of Surgeons; 2020. Available from: https://www.clinicaltrials. gov/ct2/show/NCT04356534.
Convalescent Plasma Therapy vs. SOC for the Treatment of COVID19 in Hospitalized Patients. Spain: Cristina Avendaño Solá, Puerta de Hierro University Hospital; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04345523.
Convalescent Plasma as Therapy for Covid-19 Severe SARS-CoV-2 Disease (CONCOVID Study). Netherlands: Erasmus Medical Center Rotterdam, Zuid-Holland; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04342182.
Efficacy of Convalescent Plasma Therapy in Patients with COVID-19. India: Institute of Liver and Biliary Sciences; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04425915.
Convalescent Plasma Therapy in Patients with COVID-19. Jakarta Pusat, Indonesia: Gatot Soebroto Central Army Presidential Hospital; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04407208.
Convalescent Plasma Therapy on Critically-ill Novel Coronavirus (COVID-19) Patients. Iraq: Akarkh Health Directorate Baghdad; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04441424.
Convalescent Plasma Therapy in Severe COVID-19 Infection. Bangladesh: Bangabandhu Sheikh Mujib Medical University Dhaka; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04403477.
Amotosalen-UV A Pathogen-inactivated Convalescent Plasma in Addition to Best Supportive Care and Antiviral Therapy on Clinical Deterioration in Adults Presenting with Moderate to Severe COVID-19. Basel, Switzerland: Blutspendezentrum SRK Beider Basel, University Hospital; 2020. Available from: https://www.clinicaltrials.gov/ct2/ show/NCT04389944.
Convalescent Plasma for Treatment of COVID-19: An Exploratory Dose Identifying Study. Sweden: Danderyd Hospital, Danderyd, Stockholm; 2020. Available from: https://www.clinicaltrials.gov/ct2/ show/NCT04384497.
Convalescent Plasma Treatment in COVID-19. Pakistan: Aga Khan University Hospital, Karachi, Sind; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04476888.
Evaluation of SARS-CoV-2 (COVID-19) Antibody-containing Plasma Therapy. Massachusetts, United States: Brigham and Women’s Hospital, Boston; 2020. Available from: https://www.clinicaltrials.gov/ ct2/show/NCT04361253.
Plasma Therapy of COVID-19 in Critically Ill Patients. New York, United States: Columbia University Irving Medical Center; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04359810.
Treatment of Patients with COVID-19 with Convalescent Plasma. Brazil: General Hospital, University of Sao Paulo; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04415086.
Convalescent Plasma for the Treatment of COVID-19. Philadelphia, PA, Pennsylvania, United States: Thomas Jefferson University Hospital; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04389710.
Assessment of the Effect of Convalescent Plasma Therapy in Patients With Life-threatening COVID19 Infection. Egypt: Cairo University Hospital Cairo; 2020. Available from: https://www.clinicaltrials.gov/ ct2/show/NCT04438694.
Convalescent Plasma for the Treatment of Patients with COVID-19. United States: Children’s Hospital Colorado, Aurora, Colorado; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04372368.
Convalescent Plasma as Treatment for Hospitalized Subjects with COVID-19 Infection. New Jersey, United States: Hackensack University Medical Center; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04343755.
Convalescent Plasma for the Treatment of Patients with Severe COVID-19 Infection. Attiki, Greece: Evangelismos General Hospital, Athens; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/ NCT04408209.
Convalescent Plasma as a Possible Treatment for COVID-19. Chicago, Illinois, United States: University of Illinois at Chicago; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04442191.
Treatment With Investigational Convalescent Plasma and Measure Antibody Levels in Patients Hospitalized With COVID-19. Albuquerque, New Mexico, United States: University of New Mexico Health Sciences Center; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04434131.
Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19. Albert Lea, Minnesota, United States: Mayo Clinic Health System in Albert Lea; 2020. Available from: https://www. clinicaltrials.gov/ct2/show/NCT04338360.
Experimental Expanded Access Treatment with Convalescent Plasma for the Treatment of Patients with COVID-19. Massachusetts, United States: UMass Medical School Worcester; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04445207.
Safety in Convalescent Plasma Transfusion to COVID-19. Nuevo Leon, Mexico: Hospital San José, Monterrey; 2020. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04333355.
Convalescent Plasma vs Human Immunoglobulin to Treat COVID-19 Pneumonia. Aguascalientes, Mexico: Centenario Hospital Miguel Hidalgo; 2020. Available from: https://www.clinicaltrials.gov/ct2/ show/NCT04381858.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.