View source for Covaxin

{{Short description|Vaccine against COVID-19}}
{{About|Bharat Biotech's COVID-19 vaccine| [[Novavax]]'s vaccine |Covovax|the global vaccine alliance|COVAX}}
{{Pp-semi-indef|small=yes}}
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{{Use Indian English|date=January 2021}}
{{Use dmy dates|date=February 2022}}
{{Infobox drug
| caption2           = A vial of Covaxin
| image              = COVAXIN Logo.svg
| alt                = 
| image2             = Bharat Biotech Covaxin Bangalore BESTpedia.jpg
| alt2               = 
| type               = vaccine
| target             = [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]]
| vaccine_type       = Inactivated
| tradename          = Covaxin
| Drugs.com          = 
| MedlinePlus        = 
| pregnancy_AU       = 
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Intramuscular injection|Intramuscular]]
| ATC_prefix         = J07
| ATC_suffix         = BN03
| ATC_supplemental   = 
| legal_AU           = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_CA           = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK           = 
| legal_US           = 
| legal_US_comment   = 
| legal_status       = [[List of COVID-19 vaccine authorizations#Covaxin|Full list of Covaxin authorizations]]
| CAS_number_Ref     = <ref>{{cite web|url=https://www.wipo.int/edocs/pubdocs/en/wipo-pub-1075-en-covid-19-related-vaccines-and-therapeutics.pdf|title=Patent Landscape Report COVID-19-related vaccines and therapeutics}}</ref>
| CAS_number         = 2501889-19-4
| DrugBank_Ref       = 
| UNII               = 76JZE5DSN6
| DrugBank           = DB15847
| PubChem            = 
| ChemSpiderID_Ref   = 
| ChemSpiderID       = 
}}
{{COVID-19 pandemic sidebar|expanded=medical}}

'''Covaxin''' ([[list of pharmaceutical compound number prefixes|development name]], '''BBV152''') is a [[Inactivated vaccine|whole inactivated virus]]-based [[COVID-19 vaccine]] developed by [[Bharat Biotech]] in collaboration with the [[Indian Council of Medical Research]] - [[National Institute of Virology]].<ref name="Hotez">{{cite journal | vauthors = Hotez PJ, Bottazzi ME | title = Whole Inactivated Virus and Protein-Based COVID-19 Vaccines | journal = Annual Review of Medicine | volume = 73 | issue = 1 | pages = 55–64 | date = January 2022 | pmid = 34637324 | doi = 10.1146/annurev-med-042420-113212 | s2cid = 238747462 | doi-access = free }}</ref>

On 3 November 2021, the [[World Health Organization]] (WHO) validated the vaccine for emergency use, as the first Indian-developed covid vaccine to be approved.<ref name=":1">{{cite news| vauthors = Mitra AK, Singh S |date=3 November 2021|title=India's first homegrown COVID-19 shot wins WHO emergency use listing|language=en|work=Reuters|url=https://www.reuters.com/world/india/whos-advisory-group-recommends-emergency-listing-indias-first-homegrown-covid-19-2021-11-03/|access-date=8 November 2021}}</ref><ref name="WHO PR 20211103">{{cite press release|title=WHO issues emergency use listing for eighth COVID-19 vaccine|website=World Health Organization (WHO)|url=https://www.who.int/news/item/03-11-2021-who-issues-emergency-use-listing-for-eighth-covid-19-vaccine|access-date=3 November 2021}}</ref> By 31 January 2022, Covaxin had been granted emergency use approval in 13 countries.<ref>{{cite news|title=Covaxin granted emergency use approval in 13 countries, Govt informs Parliament|website=[[India Today]]|url=https://www.indiatoday.in/coronavirus-outbreak/vaccine-updates/story/covaxin-granted-emergency-use-approval-in-13-countries-govt-informs-parliament-1908992-2022-02-04|access-date=4 February 2022}}</ref>

{{Toclimit|3}}

==Medical uses==

===Effectiveness===
A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% [[confidence interval]].<ref>{{cite journal|vauthors=Krause P, Fleming TR, Longini I, Henao-Restrepo AM, Peto R, Dean NE, Halloran ME, Huang Y, Fleming TR, Gilbert PB, DeGruttola V |display-authors=6 |date=12 September 2020 |title=COVID-19 vaccine trials should seek worthwhile efficacy |journal=The Lancet |volume=396 |issue=10253 |pages=741–743 |doi=10.1016/S0140-6736(20)31821-3 |issn=0140-6736 |pmid=32861315 |pmc=7832749 |quote=WHO recommends that successful vaccines should show an estimated risk reduction of at least one-half, with sufficient precision to conclude that the true vaccine efficacy is greater than 30%. This means that the 95% CI for the trial result should exclude efficacy less than 30%. Current US Food and Drug Administration guidance includes this lower limit of 30% as a criterion for vaccine licensure.}}</ref> Effectiveness is generally expected to slowly decrease over time.<ref>{{Cite journal |display-authors=6 |vauthors=Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP |date=May 2021 |title=Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection |journal=Nature Medicine |volume=27 |issue=7 |pages=1205–1211 |doi=10.1038/s41591-021-01377-8 |issn=1546-170X |pmid=34002089 |s2cid=234769053 |doi-access=free }}</ref>

{| class="wikitable"
|+Initial [[Phases of clinical research#Efficacy vs effectiveness|effectiveness]] by [[Variants of SARS-CoV-2|variant]]
|-
!Doses
![[Severity of illness]]
![[SARS-CoV-2 Delta variant|Delta]]
|-
!rowspan="2"|1
![[Symptoms of COVID-19|Symptomatic]]
|{{shade|color=gold|inv=1|-1|{{Estimate|-1|-51|33|unit=%|mini=auto}}{{efn-ua|name="effectiveness-ci-with-zero"|The [[confidence interval]] includes zero, so it is possible that vaccination had no effect.}}<ref name="effectiveness-delta"/>}}
|-
![[Inpatient care|Hospitalization]]
|{{n/a|Not reported}}
|-
!rowspan="2"|2
![[Symptoms of COVID-19|Symptomatic]]
|{{shade|color=gold|inv=1|50|{{Estimate|50|33|62|unit=%|mini=auto}}<ref name="effectiveness-delta">{{Cite journal |vauthors=Desai D, Khan AR, Soneja M, Mittal A, Naik S, Kodan P, Mandal A, Maher GT, Kumar R, Agarwal A, Gowda NR |display-authors=6 |date=23 November 2021 |title=Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study |journal=The Lancet Infectious Diseases |volume=22 |issue=3 |doi=10.1016/S1473-3099(21)00674-5 |issn=1473-3099 |pmid=34826383 |pmc=8610201 |at=Table 2}}</ref>}}
|-
![[Inpatient care|Hospitalization]]
|{{n/a|Not reported}}
|}
{{notelist-ua}}

===Efficacy===
A phase 3 clinical trial with 25,798 participants found that the vaccine is {{Estimate|64|29|82|unit=%|mini=no}} effective against asymptomatic cases, {{Estimate|78|65|86|unit=%|mini=yes}} effective against symptomatic disease, {{Estimate|93|57|100|unit=%|mini=yes}} effective against severe disease, and {{Estimate|65|33|83|unit=%|mini=yes}} effective against the [[Delta variant]].<ref>{{Cite journal |vauthors=Ella R, Reddy S, Blackwelder W, Potdar V, Yadav P, Sarangi V, Aileni VK, Kanungo S, Rai S, Reddy P, Verma S |display-authors=6 |date=11 November 2021 |title=Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial |journal=The Lancet |volume=398 |issue=10317 |pages=2173–2184 |doi=10.1016/S0140-6736(21)02000-6 |issn=0140-6736 |pmid=34774196|pmc=8584828 }}</ref>

==Manufacturing==
As an [[inactivated vaccine]], Covaxin uses a more traditional technology that is similar to the inactivated [[polio vaccine]]. Initially, a sample of [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]] was isolated by India's [[National Institute of Virology]] and used to grow large quantities of the virus using [[vero cell]]s. From then on, the viruses are soaked in [[beta-propiolactone]] (BPL), which deactivates them by binding to their genes, while leaving other viral particles intact. The resulting inactivated viruses are then mixed with the aluminium-based [[Immunologic adjuvant|adjuvant]] Alhydroxiquim-II.<ref name="Hotez"/><ref>{{cite news | vauthors = Corum J, Zimmer C |title=How Bharat Biotech's Vaccine Works |url=https://www.nytimes.com/interactive/2021/health/bharat-biotech-covid-19-vaccine.html |access-date=29 April 2021 |work=The New York Times |date=26 April 2021}}</ref><ref name="NIH"/>

The vaccine is produced with Bharat Biotech's in-house [[vero cell]] manufacturing platform<ref>{{cite journal | vauthors = Hoeksema F, Karpilow J, Luitjens A, Lagerwerf F, Havenga M, Groothuizen M, Gillissen G, Lemckert AA, Jiang B, Tripp RA, Yallop C | display-authors = 6 | title = Enhancing viral vaccine production using engineered knockout vero cell lines - A second look | journal = Vaccine | volume = 36 | issue = 16 | pages = 2093–2103 | date = April 2018 | pmid = 29555218 | pmc = 5890396 | doi = 10.1016/j.vaccine.2018.03.010 | doi-access = free }}</ref> that has the capacity to deliver about 300 million doses.<ref>{{cite news |title=Coronavirus vaccine update: Bharat Biotech's Covaxin launch likely in Q2 of 2021, no word on pricing yet |url=https://www.businesstoday.in/sectors/pharma/coronavirus-vaccine-update-bharat-biotech-covaxin-launch-likely-in-q2-of-2021-no-word-on-pricing-yet/story/422659.html |access-date=13 December 2020 |work=www.businesstoday.in |agency=India Today Group}}</ref> The company is in the process of setting up a second plant at its [[Genome Valley]] facility in Hyderabad to make Covaxin. The firm, in collaboration with the [[Government of Odisha]], is establishing another facility at ''Odisha Biotech Park'' in [[Bhubaneswar]] to commence Covaxin production by June 2022.<ref>{{cite web |date=7 May 2021|title=Odisha sets June 2022 deadline to begin Covaxin production at Andharua|url=https://www.livemint.com/news/india/odisha-sets-june-2022-deadline-to-begin-covaxin-production-at-andharua-11620355118755.html|access-date=19 May 2021|website=mint|language=en}}</ref><ref>{{cite news|title=Bhubaneswar: 'Expedite building of Biotech Park near city', says CS Suresh Chandra Mohapatra - Times of India|url=https://timesofindia.indiatimes.com/city/bhubaneswar/bhubaneswar-expedite-building-of-biotech-park-near-city-says-cs-suresh-chandra-mohapatra/articleshow/82451910.cms|access-date=21 May 2021|website=The Times of India|date=7 May 2021 |language=en}}</ref>

In December 2020, Ocugen entered into a partnership with Bharat Biotech to co-develop and exclusively commercialise Covaxin in the US market;<ref>{{cite news|date=22 December 2020|title=Ocugen to co-develop Bharat Biotech's COVID-19 vaccine candidate for U.S.|work=Reuters|url=https://www.reuters.com/article/health-coronavirus-ocugen-bharat-idUSKBN28W1G4|access-date=5 January 2021}}</ref><ref>{{cite news|title=Bharat Biotech, Ocugen to co-develop Covaxin for US market|work=The Economic Times|url=https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/bharat-biotech-ocugen-to-co-develop-covaxin-for-us-market/articleshow/79872249.cms?from=mdr|access-date=5 January 2021}}</ref> in June 2021, the partnership was extended to cover Canada.<ref>{{cite news | vauthors = Swati B |title=Covaxin vaccine: After US market, Bharat Biotech ties up with Ocugen for Covaxin sale in Canada |url= https://timesofindia.indiatimes.com/india/after-us-market-bharat-biotech-ties-up-with-ocugen-for-covaxin-sale-in-canada/articleshow/83206592.cms |access-date=3 July 2021 |work=The Times of India |date=3 June 2021 |language=en}}</ref> In January 2021, Precisa Medicamentos entered into an agreement with Bharat Biotech to supply Covaxin to Brazil.<ref>{{cite news |title=Bharat Biotech inks pact with Precisa Med to supply Covaxin to Brazil |url=https://www.livemint.com/news/india/bharat-biotech-inks-pact-with-precisa-med-to-supply-covaxin-to-brazil-11610456928074.html |work=mint |date=12 January 2021 }}</ref> The contract was terminated in July 2021 after the Brazilian government suspended procurement to investigate allegations of irregularities in pricing.<ref>{{cite news| url=https://indianexpress.com/article/business/bharat-biotech-nixes-covaxin-supply-pact-with-precisa-in-brazil-7419561/ |title=Bharat Biotech nixes Covaxin supply pact with Precisa in Brazil | vauthors = Raghavan P |date=24 July 2021 |publisher=Indian Express}}</ref>

In May 2021, Haffkine Bio-Pharmaceutical Corporation Limited of [[Haffkine Institute]] entered into a [[memorandum of understanding]] (MoU) with Bharat Biotech and announced that the production of Covaxin by them will commence after obtaining support from the Maharashtra state government and approval from the Indian government<ref>{{cite news |title='Will have capacity for 22.8 crore vaccine doses a year', says managing director of Haffkine Institute |url=https://www.thehindubusinessline.com/news/national/maharashtra-allows-haffkine-bio-pharma-to-manufacture-covid-vaccines/article34431710.ece |work=The Hindu Business Line |date=29 April 2021 |language=en}}</ref> whereas [[Indian Immunologicals Limited]] (IIL) has signed a commercial agreement with Bharat Biotech for producing the drug substance, a critical component of the vaccine<ref>{{cite news | vauthors = Bharadwaj S |title=Covid-19 chokes competition in Telangana: Vax makers BB, IIL join hands |url=https://timesofindia.indiatimes.com/city/hyderabad/covid-19-chokes-competition-vax-makers-bb-iil-join-hands/articleshow/82300564.cms |work=The Times of India |date=29 April 2021 |language=en}}</ref> [[Bharat Immunologicals and Biologicals Corporation]] (BIBCOL) will also manufacture the vaccine.<ref>{{cite news |title=BIBCOL to manufacture 2 crore doses of Covaxin every month in UP |url=https://www.financialexpress.com/lifestyle/health/bibcol-to-manufacture-2-crore-doses-of-covaxin-every-month-in-up/2251627/ |work=The Financial Express |date=14 May 2021}}</ref>

On 1 April 2022, Bharat Biotech announced that it was cutting production due to reduction in demand. On 2 April the WHO said that a March 2022 inspection of facilities used to manufacture Covaxin had uncovered [[good manufacturing practice]] deficiencies.<ref name="WHO GMP">{{cite journal |url=https://www.science.org/content/article/exports-indian-covid-19-vaccine-halted-after-who-finds-problems-manufacturing-plant |title=Exports of an Indian COVID-19 vaccine halted after WHO finds problems at manufacturing plant | vauthors = Pulla P |date=7 April 2022 |journal=[[Science (journal)|Science]] |doi= 10.1126/science.abq4311}}</ref>

==History==
===Clinical trials===
====Phase I and II trials====
In May 2020, Indian Council of Medical Research's ([[ICMR]]'s) [[National Institute of Virology]] approved and provided the virus strains for developing an Indian [[COVID-19]] vaccine.<ref>{{cite news |title=ICMR teams up with Bharat Biotech to develop Covid-19 vaccine |url=https://www.livemint.com/news/india/icmr-teams-up-with-bharat-biotech-to-develop-covid-19-vaccine-11589038719666.html |work=Livemint |date=9 May 2020 }}</ref><ref>{{cite news | vauthors = Chakrabarti A |title=India to develop 'fully indigenous' Covid vaccine as ICMR partners with Bharat Biotech |url=https://theprint.in/health/india-to-develop-fully-indigenous-covid-vaccine-as-icmr-partners-with-bharat-biotech/418180/ |work=ThePrint |date=10 May 2020}}</ref> In June 2020, the company received permission to conduct Phase I and Phase II human trials of a developmental [[COVID-19]] vaccine codenamed '''BBV152''', from the Drugs Controller General of India ([[DCGI]]), [[Government of India]].<ref>{{cite news |title=India's First COVID-19 Vaccine Candidate Approved for Human Trials |url=https://www.nytimes.com/reuters/2020/06/29/world/asia/29reuters-health-coronavirus-india-vaccine.html |work=The New York Times |date=29 June 2020}}</ref> A total of 12 sites were selected by the [[Indian Council for Medical Research]] for Phase I and II randomised, double-blind and placebo-controlled clinical trials of vaccine candidate.<ref>{{cite news |title=Human clinical trials of potential Covid-19 vaccine 'Covaxin' started at AIIMS |url=http://ddnews.gov.in/health/human-clinical-trials-potential-covid-19-vaccine-%E2%80%98covaxin%E2%80%99-started-aiims |work=DD News |publisher=Prasar Bharati, Ministry of I & B, Government of India |date=25 July 2020}}</ref><ref>{{cite news|date=25 July 2020|title=Asia Today: Amid new surge, India tests potential vaccine|newspaper=The Washington Post|url=https://www.washingtonpost.com/business/asia-today-skorea-records-113-new-cases-most-from-overseas/2020/07/24/21f23ad0-ce17-11ea-99b0-8426e26d203b_story.html|access-date=17 December 2020}}</ref><ref>{{cite news |title=Delhi: 30-year-old is first to get dose of trial drug Covaxin |url=https://indianexpress.com/article/india/aiims-administers-first-dose-of-bharat-biotechs-potential-covid-vaccine-to-30-yr-old-man-6521778/ |work=The Indian Express |date=25 July 2020 }}</ref>

In January 2021, the company published Phase I trial results in ''[[The Lancet]]''.<ref>{{cite journal | vauthors = Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, Ganneru B, Sapkal G, Yadav P, Abraham P, Panda S, Gupta N, Reddy P, Verma S, Kumar Rai S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Rao V, Guleria R, Ella K, Bhargava B | display-authors = 6 | title = Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial | journal = The Lancet. Infectious Diseases | volume = 21 | issue = 5 | pages = 637–646 | date = May 2021 | pmid = 33485468 | pmc = 7825810 | doi = 10.1016/S1473-3099(20)30942-7 }}</ref> On 8 March 2021, Phase II results were published in ''The Lancet''. The study showed that Phase II trials had a higher immune response and induced T-cell response due to the difference in dosing regime from Phase I. The doses in Phase II were given at 4 weeks interval as opposed to 2 weeks in Phase I. Neutralization response of the vaccine were found significantly higher in Phase II.<ref name="auto">{{cite journal | vauthors = Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, Das D, Raju D, Praturi U, Sapkal G, Yadav P, Reddy P, Verma S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Bhate A, Rai S, Panda S, Abraham P, Gupta N, Ella K, Bhargava B, Vadrevu KM | display-authors = 6 | title = Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial | journal = The Lancet. Infectious Diseases | date = March 2021 | volume = 21 | issue = 7 | pages = 950–961 | pmid = 33705727 | doi = 10.1016/S1473-3099(21)00070-0 | pmc = 8221739 | doi-access = free }}</ref>

====Phase III trials====
In November 2020, Covaxin received the approval to conduct Phase III human trials<ref>{{cite news |title=Covaxin Phase III trial from November |url=https://www.thehindu.com/business/covaxin-phase-iii-trial-from-november/article32928549.ece |work=The Hindu |date=23 October 2020 }}</ref> after completion of Phase I and II.<ref>{{cite journal | vauthors = Ganneru B, Jogdand H, Daram VK, Das D, Molugu NR, Prasad SD, Kannappa SV, Ella KM, Ravikrishnan R, Awasthi A, Jose J, Rao P, Kumar D, Ella R, Abraham P, Yadav PD, Sapkal GN, Shete-Aich A, Desphande G, Mohandas S, Basu A, Gupta N, Vadrevu KM | display-authors = 6 | title = Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation | journal = iScience | volume = 24 | issue = 4 | pages = 102298 | date = April 2021 | pmid = 33723528 | pmc = 7944858 | doi = 10.1016/j.isci.2021.102298 | bibcode = 2021iSci...24j2298G }}</ref> A randomised, double-blinded, placebo-controlled study among volunteers of age group 18 and above, it started on 25 November and involved around 26,000 volunteers from across 22 sites in India.<ref>{{cite news |title=Bharat Biotech begins Covaxin Phase III trials |url=https://indianexpress.com/article/india/bharat-biotech-begins-covaxin-phase-iii-trials-7055237/ |work=The Indian Express |date=18 November 2020 }}</ref><ref>{{cite web|title=An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers|url=https://clinicaltrials.gov/ct2/show/NCT04641481|access-date=26 November 2020|website=clinicaltrials.gov|publisher=[[United States National Library of Medicine]]|type=Registry|id=NCT04641481}}</ref><ref>{{cite news | vauthors = Sen M |title=List of states that have started phase 3 trials of India's first Covid vaccine |url=https://www.livemint.com/news/india/coronavirus-vaccine-in-india-these-states-have-started-phase-3-trials-of-bharat-biotech-covaxin-11606908773897.html |work=mint |date=2 December 2020 }}</ref> Refusal rate for Phase III trials was much higher than that for Phase I and Phase II. As a result, only 13,000 volunteers had been recruited by 22 December with the number increasing to 23,000 by 5 January.<ref name="ndtv-phase3-drop">{{cite news |url=https://www.ndtv.com/india-news/coronavirus-news-70-80-drop-in-participation-for-phase-3-trials-of-covaxin-official-2340001 |work=NDTV |date=17 December 2020 |title=70%-80% Drop in Participation For Phase 3 Trials Of Covaxin: Official}}</ref><ref name="print-incomplete-approval">{{cite news |url=https://theprint.in/health/bharat-biotechs-covaxin-given-conditional-nod-based-on-incomplete-phase-3-trial-results-data/578389/ |title=Bharat Biotech's Covaxin given conditional nod based on incomplete Phase 3 trial results data |work=The Print |date=3 January 2021}}</ref>

Multiple ethical breaches have been reported at one of their trial sites in [[Bhopal]], potentially hampering the quality of overall data.<ref>{{cite web| vauthors = Pulla P |date=9 February 2021|title=Explained: Is the Data From Covaxin Trial's Bhopal Site Tainted?|url=https://www.thequint.com/coronavirus/explained-is-the-data-from-covaxin-trials-bhopal-site-tainted-bharat-biotech-icmr|access-date=18 May 2021|website=TheQuint|language=en}}</ref><ref>{{cite web| vauthors = Bhuyan A |date=14 January 2021|title=How Covaxin Trial Participants in Bhopal Were Misled|url=https://science.thewire.in/health/peoples-hospital-bhopal-covaxin-clinical-trials-exploitation-ethics-ground-report/|access-date=18 May 2021|website=The Wire Science|language=en-GB}}</ref><ref>{{cite web|author=Esha Mitra and Julia Hollingsworth|title=More than a dozen slum residents in an Indian city say they didn't know they were part of a clinical vaccine trial|url=https://www.cnn.com/2021/02/25/asia/india-vaccine-trials-covid-ethics-intl-dst-hnk/index.html|access-date=18 May 2021|website=CNN|date=26 February 2021 }}</ref><ref>{{cite journal | vauthors = Bmj IC | title = India: Doctors call for investigation into allegations of ethical abuse in covid-19 vaccine trial | journal = BMJ | volume = 372 | pages = n131 | date = January 2021 | pmid = 33446480 | doi = 10.1136/bmj.n131 | doi-access = free }}</ref>

====US Immunobridging and booster Phase II/III trial====

In March 2022, Ocugen registered a Phase 2/3 trial for 400 people in the US to compare the immune responses to those in people in the Indian phase 3 trial, as well as safety and tolerability.<ref name="US immunobridging trial">{{ClinicalTrialsGov|NCT05258669|Immuno-bridging and Broadening Study of a Whole, Inactivated COVID-19 Vaccine BBV152 in Healthy Adults}}</ref> The trial also aims to assess the vaccine as a booster after other Covid vaccines used in the US. Ocugen paused Covaxin's bridging trial in April 2022 citing WHO inspection results.<ref>{{cite web| url=https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-provides-update-its-phase-23-study-covaxintm-bbv152 |date=12 April 2022 |title=Ocugen, Inc. Provides Update on its Phase 2/3 Study of COVAXIN™ (BBV152) |publisher=Ocugen}}</ref>

====Phase IV trials====
In June 2021, Bharat Biotech announced the start of phase IV trials to evaluate the vaccine's real-world effectiveness.<ref>{{cite news |title=Bharat Biotech plans Covaxin Phase 4 trials, says will meet 'every scientific standard' |url=https://www.cnbctv18.com/healthcare/bharat-biotech-plans-covaxin-phase-4-trials-says-will-meet-every-scientific-standard-9612031.htm |access-date=3 July 2021 |work=CNBC TV18 |date=10 June 2021 |language=en}}</ref> A study of effectiveness and hesitancy study in Healthcare Workers of [[Max Healthcare|Max Group of Hospitals]] at New Delhi from Covaxin and Covishied is under trials.<ref>{{Cite web | website=ctri.nic.in|publisher=[[Clinical Trials Registry – India|Clinical Trials Registry India]]| title=A prospective, longitudinal, observational, post licensure vaccine evaluation study to assess the effectiveness of COVID-19 vaccine among the Healthcare workers of Max group of hospitals |id=CTRI/2021/01/030782 |url=http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=52014| date=24 June 2021|access-date=3 July 2021}}</ref>

====Trials on minors====
In May 2021, Drugs Controller General of India (DCGI) approved clinical trials in the age group of 2 to 18 years.<ref>{{cite news | vauthors = Bhaduri A |title=Covaxin trials in children between 2 and 18 years to begin in 10-12 days, says Niti Aayog member |url=https://www.hindustantimes.com/india-news/covaxin-trials-in-children-between-2-and-18-years-to-begin-in-10-12-days-says-niti-aayog-member-101621339718922.html |work=Hindustan Times |date=18 May 2021 |language=en}}</ref> The trials are conducted at [[AIIMS Delhi]] and Patna.<ref>{{cite news | vauthors = Jaswal M |title=Covaxin: AIIMS Delhi to start trials on children from tomorrow, says report |url=https://www.livemint.com/news/india/covaxin-aiims-delhi-to-start-trials-on-children-from-tomorrow-says-report-11622991708152.html |work=mint |date=6 June 2021 |language=en}}</ref> As many as 54 children had registered at the [[AIIMS Patna]].<ref>{{cite news | vauthors = Kumar R |title=Covaxin trials on children begin at AIIMS-Patna |url=https://www.hindustantimes.com/cities/others/covaxin-trials-on-children-begin-at-aiimspatna-101622559658408.html |work=Hindustan Times |date=1 June 2021 |language=en}}</ref> In total 525 participants are enrolled in the study as per [[clinical trial]] data.<ref>{{Cite journal| url=https://clinicaltrials.gov/ct2/show/NCT04918797 |title=A Phase II/III, Open Label, Multicenter Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Whole-Virion Inactivated SARS-CoV-2 Vaccine (COVAXIN®) in Healthy Volunteers Ages ≤18 to ≥ 2 Years. | website=ClinicalTrials.gov | publisher=[[United States National Library of Medicine]] |date=26 May 2021 |access-date=3 July 2021 |id=NCT04918797}}</ref>

==== Variants ====
In December 2020, the [[SARS-CoV-2 Alpha variant|Alpha variant]] or lineage B.1.1.7, was identified in the UK.<ref>{{cite news | title=Inside the B.1.1.7 Coronavirus Variant | website=The New York Times | date=18 January 2021 | url=https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html | access-date=29 January 2021}}</ref> An ''[[in vitro]]'' study on this variant was carried out and preliminary results show Covaxin to be effective in neutralising this strain.<ref>{{cite journal | vauthors = Sapkal GN, Yadav PD, Ella R, Deshpande GR, Sahay RR, Gupta N, Vadrevu KM, Abraham P, Panda S, Bhargava B | display-authors = 6 | title = Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B.1.1.7 variant of SARS-CoV-2 | journal = Journal of Travel Medicine | volume = 28 | issue = 4 | date = June 2021 | pmid = 33772577 | pmc = 8083765 | doi = 10.1093/jtm/taab051 | doi-access = free }}</ref>

In April 2021, the [[Indian Council of Medical Research]] reported that the vaccine has shown promising results in neutralising [[lineage B.1.617]].<ref>{{cite news | vauthors = Mascarenhas A |title=Covaxin neutralises double mutant strain of SARS-CoV-2: ICMR study |url=https://indianexpress.com/article/india/covaxin-neutralises-double-mutant-strain-icmr-study-7282835/ |work=The Indian Express |date=21 April 2021 }}</ref><ref>{{cite journal | vauthors = Yadav PD, Sapkal GN, Abraham P, Ella R, Deshpande G, Patil DY, Nyayanit DA, Gupta N, Sahay RR, Shete AM, Panda S, Bhargava B, Mohan VK | display-authors = 6 | title = Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees | journal = Clinical Infectious Diseases | date = May 2021 | volume = 74 | issue = 2 | pages = 366–368 | pmid = 33961693 | doi = 10.1093/cid/ciab411 }}</ref>

In May 2021, a joint investigation by the scientists of the [[National Institute of Virology]], found the vaccine effective in neutralising the Zeta variant or lineage P.2 (previously known as B.1.1.28).<ref>{{cite journal | vauthors = Sapkal G, Yadav PD, Ella R, Abraham P, Patil DY, Gupta N, Panda S, Mohan VK, Bhargava B | display-authors = 6 | title = Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of inactivated COVID-19 vaccine Covaxin | journal = Journal of Travel Medicine | date = May 2021 | volume = 28 | issue = 7 | pmid = 34002240 | doi = 10.1093/jtm/taab077 | pmc = 8194512 | doi-access = free }}</ref>

In June 2021, a group of researchers at the [[National Institute of Virology]] (NIV) India, collected [[Serum (blood)|sera]] from recovered patients and  people who had received the Covaxin. They found the vaccine to be effective in neutralising the Delta ([[B.1.617.2]]) and Beta ([[B.1.351]]) variants.<ref>{{cite news | vauthors = Sarkar S |title=Covaxin effective in neutralising Delta, Beta variants of Covid-19: Study |url=https://www.hindustantimes.com/india-news/covaxin-effective-in-neutralising-delta-beta-variants-of-covid-19-study-101623233592645.html |work=Hindustan Times |date=9 June 2021 |language=en}}</ref><ref>{{cite bioRxiv |vauthors=Yadav PD, Sapkal GN, Ella R, Sahay RR, Nyayanit DA, Patil DY, Deshpande G, Shete AM, Gupta N, Mohan VK, Abraham P, Panda S, Bhargava B |display-authors=6 |title=Neutralization against B.1.351 and B.1.617.2 with sera of COVID-19 recovered cases and vaccinees of BBV152 |date=7 June 2021 |biorxiv=10.1101/2021.06.05.447177}}</ref> Later, the US [[National Institute of Health]] also approved the findings where the adjuvant used was developed jointly with funding from [[NIH]].<ref>{{cite news |title=India's Covaxin effectively neutralises Delta variant of Covid: US' National Institute of Health |url=https://indianexpress.com/article/world/indias-covaxin-effectively-neutralises-delta-variant-of-covid-us-national-institute-of-health-7382053/ |work=The Indian Express |date=30 June 2021 |language=en}}</ref><ref name="NIH">{{cite news|title=Adjuvant developed with NIH funding enhances efficacy of India's COVID-19 vaccine |url=https://www.nih.gov/news-events/news-releases/adjuvant-developed-nih-funding-enhances-efficacy-indias-covid-19-vaccine |work=National Institutes of Health (NIH) |date=29 June 2021 |language=EN}} {{Include-NIH}}</ref>

== Authorisations ==
{{#section:List of COVID-19 vaccine authorizations|covaxinauthmap}}
{{See also|List of COVID-19 vaccine authorizations#Covaxin|COVID-19 vaccine#Trial and authorization status}}

=== India ===
[[File:Bharat Biotech Covaxin Bangalore BESTpedia.jpg|200px|right|thumb|A vial of Covaxin used at a private hospital in Bengaluru, India]]
On 6 December 2020, [[Bharat Biotech]] applied to the [[Drugs Controller General of India]] (DCGI), seeking emergency use authorisation.<ref>{{cite news | vauthors = Ghosh N |title=Bharat Biotech seeks emergency use authorization for Covid-19 vaccine |url=https://www.hindustantimes.com/india-news/bharat-biotech-seeks-emergency-use-authorization-for-covid-19-vaccine-govt-source/story-HmmD0JnniJeigdF6xmjxBO.html |work=Hindustan Times |date=7 December 2020 }}</ref> It was the third firm after [[Serum Institute of India]] and [[Pfizer]] to apply under such provision.<ref>{{cite news |title=After SII, Bharat Biotech seeks DCGI approval for Covaxin |url=https://www.thehindu.com/sci-tech/health/coronavirus-serum-institute-seeks-emergency-use-approval-for-covishield-in-india/article33265921.ece |work=The Hindu |date=7 December 2020 }}</ref>

On 2 January 2021, the [[Central Drugs Standard Control Organisation]] (CDSCO) recommended permission,<ref name="rec">{{cite news |title=Expert panel recommends granting approval for restricted emergency use of Bharat Biotech's Covaxin |url=https://indianexpress.com/article/india/bharat-biotechs-covaxin-covid-vaccine-approval-cdsco-7130213/ |work=The Indian Express |date=2 January 2021 }}</ref> which was granted the next day.<ref>{{cite news|date=3 January 2021|title=Coronavirus: India approves vaccines from Bharat Biotech and Oxford/AstraZeneca|work=BBC News|url=https://www.bbc.com/news/world-asia-india-55520658|access-date=3 January 2021}}</ref> Covaxin was to be used in a "clinical trial mode" i.e. the public vaccination drive was to be an open-label, single-arm clinical trial in itself.<ref name=":0">{{cite web| vauthors = Mukunth V |date=29 January 2021|title=Covaxin Trial's Info Sheet Skips Mention of Two Rare but Known Risks|url=https://science.thewire.in/health/covaxin-phase-3-clinical-trials-information-sheet-ade-vaerd-informed-consent/|access-date=18 May 2021|website=The Wire Science|language=en-GB}}</ref> This emergency approval, granted without considering Phase III trial data concerning efficacy and safety, drew widespread criticism.<ref>{{cite web |url=https://science.thewire.in/health/covaxin-covishield-indian-government-rollout-peoples-hospital-phase-3-clinical-trials-centralisation-pm-cares/ |title=Disputes Mount, but Heedless Govt Intent on Rolling Vaccine Candidates Out |date=12 January 2021 |work=The Wire}}</ref><ref>{{cite journal | vauthors = Thiagarajan K | title = What do we know about India's Covaxin vaccine? | journal = BMJ | volume = 373 | pages = n997 | date = April 2021 | pmid = 33879478 | doi = 10.1136/bmj.n997 | doi-access = free }}</ref><ref>{{cite web| vauthors = Pulla P |date=5 January 2021|title=Scientists criticize 'rushed' approval of Indian COVID-19 vaccine without efficacy data|url=https://www.science.org/content/article/scientists-criticize-rushed-approval-indian-covid-19-vaccine-without-efficacy-data|access-date=18 May 2021|website=Science {{!}} AAAS|language=en}}</ref> On 12 October 2021, Bharat Biotech's Covaxin got approved for usage on children between 2 and 18 years of age.<ref>{{Cite web|date=12 October 2021|title=COVID-19: Covaxin Vaccine Approved For Children Between 2 to 18|url=https://www.thelivemirror.com/covaxin-approved-for-children-between-2-to-18/|access-date=12 October 2021|website=The Live Mirror|language=en-US}}</ref>

=== Other nations ===
The vaccine was also approved for emergency use in Iran and Zimbabwe.<ref name="HT Zimbabwe">{{cite news| vauthors = Manral K | date=4 March 2021|title=Zimbabwe approves Covaxin, first in Africa to okay India-made Covid-19 vaccine|work=Hindustan Times|url=https://www.hindustantimes.com/world-news/zimbabwe-approves-covaxin-first-in-africa-to-okay-india-made-covid-19-vaccine-101614859597880.html|access-date=6 March 2021}}</ref><ref name="IRNA Iran">{{cite news |title=Iran issues permit for emergency use for three other COVID-19 vaccines: Official |url=https://en.irna.ir/news/84233593/Iran-issues-permit-for-emergency-use-for-three-other-COVID-19 |work=IRNA English |date=17 February 2021 }}</ref> Nepal granted {{abbr|EUA|emergency use authorization}} for Covaxin on 19 March 2021.<ref name="covax-nep">{{cite news| vauthors = Sharma G |date=19 March 2021|title=Nepal becomes third country to give emergency nod to Indian vaccine COVAXIN|work=Reuters|url=https://www.reuters.com/article/health-coronavirus-nepal-india-idUSKBN2BB1KN|access-date=19 March 2021}}</ref> On 7 April, Mexico granted emergency authorisation for Covaxin.<ref>{{cite news |date=7 April 2021|title=Mexico authorizes emergency use of Indian COVID-19 vaccine|work=Reuters|url=https://www.reuters.com/article/health-coronavirus-mexico-india-idUSKBN2BU04N|access-date=7 April 2021}}</ref> On 19 April 2021, Philippines granted EUA to Covaxin.<ref name="covaxin-ph">{{cite news |title=Covaxin, Janssen approved for emergency use in PH |url=https://cnnphilippines.com/news/2021/4/19/covaxin-janssen-emergency-use-authorization.html |publisher=CNN Philippines |date=19 April 2021 |access-date=19 April 2021 |archive-date=20 April 2021 |archive-url=https://web.archive.org/web/20210420034939/https://cnnphilippines.com/news/2021/4/19/covaxin-janssen-emergency-use-authorization.html |url-status=dead }}</ref> Additionally, Covaxin was granted EUA in Guatemala, Nicaragua, Guyana, Venezuela and Botswana.<ref name="cov-200421">{{cite web|url=https://timesofindia.indiatimes.com/india/covid-19-bharat-biotech-ramps-up-covaxin-capacity-to-700-million-doses-per-annum/articleshow/82162467.cms|title=Covid-19: Bharat Biotech ramps up Covaxin capacity to 700 million doses per annum|publisher=Times of India|date=20 April 2021| vauthors = Bharadwaj S }}</ref>

On 31 March, the [[Brazilian Health Regulatory Agency|Brazilian health regulator Anvisa]] rejected Bharat Biotech's application for supplying Covaxin in the country due to non-compliance with manufacturing norms. Bharat Biotech stated that they would re-apply after meeting the requirements.<ref>{{cite news|url=https://www.ndtv.com/india-news/brazil-says-no-to-covaxin-bharat-biotech-explains-2403218|title=Brazil Says "No" To Covaxin, Bharat Biotech Explains| vauthors = Som V |date=31 March 2021|access-date=18 April 2021|work=NDTV}}</ref> On 4 June, Anvisa approved exceptional imports of Covaxin, imposing conditions that restrict it mainly to healthy adults and limiting it to just 1% of the country's population to manage the risks through control and supervision of side effects. Anvisa cited as main concerns the incomplete phase III study, a short 45-day follow-up, which should be 60 days to meet the international consensus, and a novel [[imidazoquinoline]] [[Immunologic adjuvant|adjuvant]] that may increase the chance of developing an autoimmune disease.<ref>{{cite news | vauthors = Mcgeever J, Paraguassu L |title=Brazil's Anvisa approves Russian Sputnik V vaccine, with conditions |url=https://www.reuters.com/world/americas/brazil-health-regulator-technical-staff-recommend-conditions-any-approval-2021-06-04/ |access-date=5 June 2021 |work=Reuters |date=4 June 2021}}</ref><ref>{{cite news |title=Anvisa aprova, com restrições, a importação excepcional de doses da Covaxin e Sputnik V |trans-title=Anvisa approves import of doses of Covaxin and Sputnik V, with restrictions |url=https://g1.globo.com/bemestar/vacina/noticia/2021/06/04/anvisa-covaxin-sputnik-v.ghtml |access-date=4 June 2021 |work=G1 |agency=Globo |date=4 June 2021 |language=Portuguese}}</ref><ref>{{cite news | vauthors = Alegretti L, Barifouse R |title=Covaxin e Sputnik V: O que muda na vacinação do Brasil com decisão da Anvisa |trans-title=Covaxin and Sputnik V: What changes in vaccination in Brazil after Anvisa's decision |url=https://www.bbc.com/portuguese/brasil-57358261 |access-date=5 June 2021 |work=BBC Brasil |date=4 June 2021 |language=Portuguese}}</ref> On 30 June, Brazilian regulators suspended the deal and an investigation was opened into it by federal prosecutors to probe accusations of irregularity.<ref>{{cite news |url=https://www.thehindu.com/news/international/brazil-to-suspend-vaccine-deal-with-india-as-graft-allegations-probed/article35046662.ece |title=Brazil to suspend vaccine deal with India as graft allegations probed |date=30 June 2021 |access-date=30 June 2021 |work=The Hindu |agency=Reuters}}</ref> Anvisa cancelled an ongoing clinical trial of the vaccine on 26 July<ref>{{cite news |title=Brazil health regulator cancels clinical study for Bharat Biotech vaccine |url=https://www.reuters.com/world/americas/brazil-health-regulator-cancels-clinical-study-bharat-biotech-vaccine-2021-07-26/ |access-date=16 November 2021 |work=Reuters |date=26 July 2021}}</ref> and suspended the temporary authorization and the import and distribution permit on 27 July.<ref>{{cite news |title=Brazil suspends import permit for Bharat Biotech's COVID-19 vaccine |url=https://www.reuters.com/world/india/brazil-suspends-import-permit-bharat-biotechs-covid-19-vaccine-2021-07-27/ |access-date=16 November 2021 |work=Reuters |date=27 July 2021}}</ref>

Mauritius received its first commercial supply of Covaxin on 18 March 2021.<ref name="BB Mauritius">{{cite news|url=https://www.lexpress.mu/article/390493/dr-jagutpal-une-cargaison-200-000-vaccins-covaxin-debarque-demain|publisher=L'Express|title=Dr Jagutpal: Une cargaison de 200 000 vaccins Covaxin débarque demain | language = fr | trans-title = Dr Jagutpal: Shipment of 200,000 Covaxin vaccines lands tomorrow |newspaper=Lexpress.mu |date=19 March 2021| author = The Editorial Board }}</ref>

On 29 March 2021, [[Paraguay]] received 100,000 doses of Covaxin.<ref>{{cite web |url=https://health.economictimes.indiatimes.com/news/industry/india-provides-100000-doses-of-covaxin-to-paraguay/81754661 |title=India provides 100,000 doses of Covaxin to Paraguay |date=30 March 2021}}</ref>

In June 2021, Argentina agreed to buy 10 million doses of Covaxin and administer them to its citizens.<ref>{{cite web|url=https://www.batimes.com.ar/news/argentina/buenos-aires-province-agrees-to-buy-10-million-doses-of-covaxin-vaccine.phtml|title=Buenos Aires Province agrees to buy 10 million doses of Covaxin vaccine|publisher=BAT Times|date=4 June 2021}}</ref>

On 3 November 2021, the [[World Health Organization]] (WHO) validated the vaccine for emergency use.<ref name=":1" /><ref name="WHO PR 20211103"/> A subsequent inspection of manufacturing facilities led WHO to suspend procurement of Covaxin through UN agencies in April 2022.<ref name="WHO GMP" />

== See also ==
* [[BBV154]]
* [[Case Covaxin|Case Covaxin (Brazil)]]
* [[COVID-19 vaccination in India]]

== References ==
{{Reflist}}

== External links ==
{{scholia|Q98703813}}
* {{cite news | title=How Bharat Biotech's Vaccine Works | website=The New York Times | date=4 January 2021 | url=https://www.nytimes.com/interactive/2021/health/bharat-biotech-covid-19-vaccine.html | vauthors = Corum J, Zimmer C }}

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[[Category:Indian COVID-19 vaccines]]
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