Pfizer–BioNTech COVID-19 vaccine

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"Pfizer vaccine" and "BioNTech vaccine" redirect here. For the manufacturers, see Pfizer and BioNTech.
File:Covid19 vaccine biontech pfizer 3.jpg
A vial of the Pfizer–BioNTech COVID‑19 vaccine for the U.S. market
Vaccine description
Target disease SARS-CoV-2
Type ?
Clinical data
Pronunciation Tozinameran: /ˌtoʊzɪˈnæmərən/ toh-ZIH-nam-ƏR-ən
Comirnaty: /koʊˈmɜːrnəti/ KOH-mur-NƏ-tee[18]
Trade names Comirnaty[13][6][17]
AHFS/Drugs.com
MedlinePlus a621003
Licence data EMA:Link, US Daily Med:link
Pregnancy
category
Legal status

ZA: Section 21 [14][15]

Others: List of Pfizer-BioNTech COVID-19 vaccine authorizations
Routes of
administration		 Intramuscular
Identifiers
CAS Number 2417899-77-3
ATC code None
PubChem SID: 434370509
DrugBank DB15696
UNII 5085ZFP6SJ
KEGG D11971

Lua error in package.lua at line 80: module 'strict' not found. The Pfizer–BioNTech COVID-19 vaccine (INN: tozinameran), sold under the brand name Comirnaty,[6] is an mRNA-based COVID-19 vaccine developed by the German company BioNTech. It is authorized for use in people aged 12 years and older in some jurisdictions and for people 16 years and older in other jurisdictions,[6][5][10][20][21] to provide protection against infection by the SARS-CoV-2 virus, which causes COVID-19.[6][10] For its development BioNTech collaborated with Pfizer, an American company, for support with clinical trials, logistics, and manufacturing.[22][23] In China, BioNTech is partnered with China-based Fosun Pharma for development, marketing, and distribution rights and the vaccine is colloquially described as the Fosun–BioNTech COVID‑19 vaccine.[24][25][26][27][28][29][30] The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles.[31] Vaccination requires two doses given three weeks apart.[32][33][34]

Clinical trials began in April 2020[35]; by November 2020, the vaccine entered Phase III clinical trials, with over 40,000 people participating.[36] An interim analysis of study data showed a potential efficacy of 91.3% in preventing infection within seven days of a second dose.[34][37] The most common side effects include mild to moderate pain at the injection site, fatigue, and headaches.[38][39] Reports of serious side effects, such as allergic reactions, are very rare;[lower-alpha 1] no long-term complications have been reported.[6][41] Monitoring of the primary outcomes from the trials will continue until August 2021, while monitoring of the secondary outcomes will continue until January 2023.[32]

The vaccine was the first COVID‑19 vaccine to be authorized by a stringent regulatory authority for emergency use[42][43] and the first cleared for regular use.[13] In December 2020, the United Kingdom was the first country to authorize its use on an emergency basis.[41] It is authorized for use at some level in 84 countries including the United States and Canada, countries in the European Union, the United Kingdom, Australia, Ukraine, Israel, Brazil, Bangladesh, Mexico, Japan and Singapore.[44][45][46][47]

As of 30 March 2021, Pfizer and BioNTech aimed to manufacture about 2.5 billion doses in 2021.[48][49] BioNTech and Pfizer have advance purchase agreements of about US$3 billion to provide a licensed vaccine in the United States, the European Union, the United Kingdom, Japan, Canada, Peru, Singapore and Mexico.[50][51] Distribution and storage is a logistical challenge because the vaccine needs to be stored at extremely low temperatures.[52] BioNTech and Pfizer are testing a freeze-dried version that would not need ultracold storage.[53]

Medical uses

The Pfizer–BioNTech COVID-19 vaccine is used to provide protection against infection by the SARS-CoV-2 virus in order to prevent COVID-19.[6][10]

Development and funding

Before COVID‑19 vaccines, a vaccine for an infectious disease had never before been produced in less than several years, and no vaccine existed for preventing a coronavirus infection in humans.[54] The SARS-CoV-2 virus, which causes COVID‑19, was detected in December 2019,[55] and BioNTech began development of a COVID‑19 vaccine on 10 January 2020, when the SARS-CoV-2 genetic sequences were released by the Chinese Center for Disease Control and Prevention via GISAID,[56][57][58] triggering an urgent international response to prepare for an outbreak and hasten development of preventive vaccines.[59][60]

The vaccine's development began when BioNTech founder Uğur Şahin read an article in the medical journal The Lancet that convinced him the COVID‑19 coronavirus in China would soon become a global pandemic, so he called for scientists at the company to cancel their vacations and start development of a COVID‑19 vaccine in January 2020.[61] BioNTech started its program 'Project Lightspeed' to develop a vaccine against the new COVID‑19 virus based on its already established mRNA-technology,[36] which they had been developing since leading mRNA researcher Katalin Karikó joined the company in 2013.[62] Several variants of the vaccine were created in their laboratories in Mainz, and 20 of those were presented to experts of the Paul Ehrlich Institute in Langen.[63]

Funding

BioNTech received a US$135 million investment from Fosun in March 2020, in exchange for 1.58 million shares in BioNTech and the future development and marketing rights of BNT162b2 in China.[25][24]

In April 2020, BioNTech signed a partnership with Pfizer and received $185 million, including an equity investment of approximately $113 million.[64][65][66]

In June 2020, BioNTech received €100 million (US$119 million) in financing from the European Commission and European Investment Bank.[67] In September 2020, the German government granted BioNTech €375 million (US$445 million) for its COVID‑19 vaccine development program.[68]

Pfizer CEO Albert Bourla said he decided against taking funding from the US government's Operation Warp Speed for the development of the vaccine "because I wanted to liberate our scientists [from] any bureaucracy that comes with having to give reports and agree how we are going to spend the money in parallel or together, etc." Pfizer did enter into an agreement with the US for the eventual distribution of the vaccine, as with other countries.[69]

Clinical trials and vaccine efficacy

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See also: COVID-19 vaccine § Clinical trials started in 2020
File:BNT162b2 vaccine efficacy data.png
Cumulative incidence curves for symptomatic COVID‑19 infections after the first dose of the Pfizer–BioNTech vaccine (tozinameran) or placebo in a double-blind clinical trial. (red: placebo; blue: tozinameran)[70]

Phase I–II Trials were started in Germany on 23 April 2020, and in the U.S. on 4 May 2020, with four vaccine candidates entering clinical testing.[35][36] The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech.[71] Before choosing BNT162b2, BioNTech and Pfizer had conducted Phase I trials on BNT162b1 in Germany and the United States, while Fosun performed a Phase I trial in China. In these Phase I studies, BNT162b2 was shown to have a better safety profile than the other three BioNTech candidates.[72][31][73][74]

The Pivotal Phase II–III Trial with the lead vaccine candidate "BNT162b2" began in July. Preliminary results from Phase I–II clinical trials on BNT162b2, published in October 2020, indicated potential for its safety and efficacy.[31] During the same month, the European Medicines Agency (EMA) began a periodic review of BNT162b2.[75]

The study of BNT162b2 is a continuous-phase trial in Phase III as of November 2020.[32] It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals".[32] The study expanded during mid-2020 to assess efficacy and safety of BNT162b2 in greater numbers of participants, reaching tens of thousands of people receiving test vaccinations in multiple countries in collaboration with Pfizer and Fosun.[34][24]

The Phase III trial assesses the safety, efficacy, tolerability, and immunogenicity of BNT162b2 at a mid-dose level (two injections separated by 21 days) in three age groups: 12–15 years, 16–55 years or above 55 years.[32] The Phase III results indicating a 95% efficacy of the developed vaccine were published on 18 November 2020.[36] For approval in the EU, an overall vaccine efficacy of 95% was confirmed by the EMA.[76] The EMA clarified that the second dose should be administered three weeks after the first dose.[77]

Vaccine efficacy – After dose 1 or dose 2 overall, and after dose 2 overall and by age groups[76]
Efficacy endpoint Vaccine efficacy (95% confidence interval)
After dose 1 and before dose 2 52.4% (29.5–68.4%)
≥10 days after dose 1 and before dose 2 86.7% (68.6–95.4%)
After dose 2 and within 7 days after 90.5% (61.0–98.9%)
≥7 days after dose 2 94.8% (89.8–97.6%)
Overall 95.0% (90.0–97.9%)
16–55 years 95.6% (89.4–98.6%)
≥55 years 93.7% (80.6–98.8%)
≥65 years 94.7% (66.7–99.9%)

The ongoing Phase III trial, which is scheduled to run from 2020 to 2022, is designed to assess the ability of BNT162b2 to prevent severe infection, as well as the duration of immune effect.[34][78][79]

During pregnancy, breastfeeding and in babies

Based on the results of a preliminary study, the U.S. Centers for Disease Control and Prevention (CDC) recommends that pregnant people get vaccinated with the COVID‑19 vaccine.[80][81]

Pfizer and BioNTech started a Phase II–III randomized control trial in healthy pregnant women 18 years of age and older (NCT04754594).[82] The study will evaluate 30 µg of BNT162b2 or placebo administered via intramuscular injection in two doses, 21 days apart. The Phase II portion of the study will include approximately 350 pregnant women randomized 1:1 to receive BNT162b2 or placebo at 27 to 34 weeks' gestation. The Phase III portion of this study will assess the safety, tolerability, and immunogenicity of BNT162b2 or placebo among pregnant women enrolled at 24 to 34 weeks' gestation. Pfizer and BioNTech announced on 18 February 2021 that the first participants received their first dose in this trial.[83]

A study published in March 2021, in the American Journal of Obstetrics and Gynecology came to the conclusion that messenger RNA vaccines against the novel coronavirus, such as the Pfizer-BioNTech and Moderna vaccines were safe and effective at providing immunity against infection to pregnant and breastfeeding mothers. Furthermore, they found that naturally occurring antibodies created by the mother's immune system were passed on to their children via the placenta and/or breastmilk, thus resulting in passive immunity among the child, effectively giving the child protection against the disease. The study also found that vaccine-induced immunity among the study's participants was stronger in a statistically significant way over immunity gained through recovery from a natural COVID‑19 infection. In addition, the study reported that the occurrence and intensity of potential side effects in those undergoing pregnancy or lactating was very similar to those expected from non-pregnant populations, remaining generally very minor and well tolerated, mostly including injection site soreness, minor headaches, muscles aches or fatigue for a short period of time.[84]

In children and adolescents

In January 2021, Pfizer said it had finished enrolling 2,259 children aged between 12–15 years to study the vaccine's safety and efficacy.[85] On 31 March 2021, Pfizer and BioNTech announced from initial Phase III trial data that the vaccine is 100% effective for those aged 12 to 15 years of age, with trials for those younger still in progress.[86] On 10 May 2021, the vaccine was granted an emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for those aged 12 to 15 years of age.[87][88][89] A statement by the British Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) reported that the two agencies had reached a conclusion that the vaccine is safe and effective in this age group.[90][91]

In immunocompromised individuals

A 2021 report by the New South Wales government in Australia found that the Pfizer-BioNTech vaccine was safe for those suffering from various forms of immunodeficiency or immunosuppression, though it does note that the data on said groups is limited, due to their exclusion from many of the vaccine earlier trials held in 2020. It notes that the World Health Organization advises that the vaccine is among the three COVID-19 vaccines (alongside that of Moderna and AstraZeneca) it deems safe to give to immunocompromised individuals, and that expert consensus generally recommends their vaccination. The report states that the vaccines were able to generate an immune response in those individuals, though it does also note that this response is weaker than in those that are not immunocompromised. It recommends that specific patient groups, such as those suffering from cancer, inflammatory bowel disease and various liver diseases be prioritised in the vaccination schedules over other patients that do not suffer from said conditions.[92]

A research letter published in JAMA reported that the vaccines appeared to be safe for immunosuppressed organ transplant recipients, but that the resulting antibody response was considerably poorer than in the non-immunocompromised population after only one dose. The paper admitted the limitation of only reviewing the data following the first dose of a two-dose cycle vaccine.[93]

Against variants

Unless indicated otherwise, effectiveness ratings are indicative of clinical effectiveness 2 weeks after the second dose:

Effectiveness by disease severity
Variant Asymptomatic Symptomatic Hospitalization
Alpha 90% (86–92%)[94] 93% (90–96%)[95] 100% (82–100%)[94]
Beta 75% (71–79%)[94] Not reported 100% (74–100%)[94]
Gamma Not reported Not reported Not reported
Delta Not reported 88% (78–93%)[95] Not reported

A case-control study published in May 2021, in The New England Journal of Medicine found that, among vaccine recipients in Qatar, the Pfizer-BioNTech vaccine had an effectiveness of 89.5% against any documented cases of the Alpha variant (lineage B.1.1.7) and 75% effectiveness against the Beta variant (lineage B.1.351). The same study reported that the effectiveness of the vaccine against severe, critical, or fatal disease against any variant of SARS-CoV-2 was 97.4%.[94] A study carried out by Public Health England between April and May 2021 reported that the vaccine had an 88% effectiveness rate against the Delta variant (lineage B.1.617.2) and 93% effectiveness against the Alpha variant.[95]

Vaccine technology

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See also: RNA vaccine and COVID-19 vaccine § Technology platforms

The BioNTech technology for the BNT162b2 vaccine is based on use of nucleoside-modified mRNA (modRNA) which encodes a mutated form of the full-length spike protein found on the surface of the SARS-CoV-2 virus,[96] triggering an immune response against infection by the virus protein.[71]

Sequence

The modRNA sequence of the vaccine is 4,284 nucleotides long.[97] It consists of a five-prime cap; a five prime untranslated region derived from the sequence of human alpha globin; a signal peptide (bases 55–102) and two proline substitutions (K986P and V987P, designated "2P") that cause the spike to adopt a prefusion-stabilized conformation reducing the membrane fusion ability, increasing expression and stimulating neutralizing antibodies;[31][98] a codon-optimized gene of the full-length spike protein of SARS-CoV-2 (bases 103–3879); followed by a three prime untranslated region (bases 3880–4174) combined from AES and mtRNR1 selected for increased protein expression and mRNA stability[99] and a poly(A) tail comprising 30 adenosine residues, a 10-nucleotide linker sequence, and 70 other adenosine residues (bases 4175–4284).[97] The sequence contains no uridine residues; they are replaced by 1-methyl-3'-pseudouridylyl.[97] The 2P proline substitutions in the spike proteins were originally developed for a MERS vaccine by researchers at the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, Scripps Research, and Jason McLellan's team (at the University of Texas at Austin, previously at Dartmouth College).[98]

Composition

In addition to the mRNA molecule, the vaccine contains the following inactive ingredients (excipients):[7][100][101]

The first four of these are lipids. The lipids and modRNA together form nanoparticles that act as adjuvants.[102] ALC-0159 is a polyethylene glycol conjugate, i.e., a PEGylated lipid.[103]

The vaccine is supplied in a multidose vial as "a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection".[10][11] It must be thawed to room temperature and diluted with normal saline before administration.[11]

Authorizations

     Full authorization

     Emergency authorization

     Eligible COVAX recipient

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See also: List of COVID-19 vaccine authorizations § Pfizer–BioNTech

Expedited

The United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave the vaccine "rapid temporary regulatory approval to address significant public health issues such as a pandemic" on 2 December 2020, which it is permitted to do under the Medicines Act 1968.[42] It was the first COVID‑19 vaccine to be approved for national use after undergoing large scale trials,[104] and the first mRNA vaccine to be authorized for use in humans.[42][105] The United Kingdom thus became the first Western country to approve a COVID‑19 vaccine for national use,[106] although the decision to fast-track the vaccine was criticised by some experts.[107]

On 8 December 2020, Margaret "Maggie" Keenan, 90, from Fermanagh, became the first person to receive the vaccine outside of a clinical trial.[108] In a notable example of museums documenting the pandemic, the vial and syringe used for that first dose were saved and acquired by The Science Museum in London for its permanent collection.[109] By 20 December, 521,594 UK residents had received the vaccine as part of the national vaccination programme. 70% of the recipients were people aged 80 or over.[110]

After the United Kingdom, the following countries and regions expedited processes to approve the Pfizer–BioNTech COVID‑19 vaccine for use: Argentina,[111] Australia,[112] Bahrain,[113] Canada,[4][114] Chile,[115] Costa Rica,[116] Ecuador,[115] Hong Kong,[117] Iraq,[118] Israel,[119] Jordan,[120] Kuwait,[121] Malaysia,[122] Mexico,[123][124] Oman,[125] Panama,[126] the Philippines,[127] Qatar,[128] Saudi Arabia,[129][130][131] Singapore,[132][133][134] South Korea,[135][136] the United Arab Emirates,[137] the United States,[9] and Vietnam.[138]

The World Health Organization (WHO) authorized it for emergency use.[139][140]

In the United States, an emergency use authorization (EUA) is "a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID‑19 pandemic", according to the FDA.[141] Pfizer applied for EUA on 20 November 2020[142] and the FDA approved the application three weeks later on 11 December 2020. Following the EUA issuance, BioNTech and Pfizer are expected to continue the Phase III clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) of the vaccine in the United States.[141][88][89] The United States Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) approved recommendations for vaccination of those aged sixteen years or older.[143][144]

On 16 February 2021, the South African Health Products Regulatory Authority (SAHPRA) in South Africa issues Section 21, Emergency Use Approval for the vaccine.[145][146]

On 31 March 2021, the Turkish ministry of health gave Emergency Use Approval for the vaccine.[citation needed]

On 5 May 2021, Health Canada authorized the vaccine for people aged 12 to 15.[5][147] On 10 May 2021, the US FDA authorized the vaccine for people aged 12 to 15 under an expanded EUA.[87][88][89][148][149] The FDA recommendation was endorsed by the ACIP and adopted by the CDC on 12 May.[150][151] On 18 May 2021, Singapore's Health Sciences Authority authorized the vaccine for people aged 12 to 15.[152] The European Medicines Agency followed suit on 28 May 2021.[153] On 4 June, the British MHRA came to a similar decision and approved the use of the vaccine for 12-15 year olds within the United Kingdom.[90][91]

Standard

On 19 December 2020, the Swiss Agency for Therapeutic Products (Swissmedic) approved the Pfizer–BioNTech COVID‑19 vaccine for regular use, two months after receiving the application, saying the vaccine fully complied with the requirements of safety, efficacy and quality. This is the first authorization under a standard procedure.[13][154] On 23 December, a Lucerne resident, a 90-year-old woman, became the first person to receive the vaccine in Switzerland.[155] This marked the beginning of mass vaccination in continental Europe.[156]

On 21 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended granting conditional marketing authorization for the Pfizer–BioNTech COVID‑19 vaccine under the brand name Comirnaty.[6][157][158] The recommendation was accepted by the European Commission the same day.[157][159]

On 23 February 2021, the Brazilian Health Regulatory Agency approved the Pfizer–BioNTech COVID‑19 vaccine under its standard marketing authorization procedure. It became the first COVID‑19 vaccine to receive definitive registration rather than emergency use authorization in the country.[160]

Adverse effects

The side effect profile of the Pfizer–BioNTech COVID‑19 vaccine is similar to that of other adult vaccines.[34] During clinical trials, the side effects deemed very common[lower-alpha 1] are (in order of frequency): pain and swelling at the injection site, tiredness, headache, muscle aches, chills, joint pain, and fever.[101] Fever is more common after the second dose.[101]

Severe allergic reaction has been observed in approximately eleven cases per million doses of vaccine administered.[161][162] According to a report by the US Centers for Disease Control and Prevention, 71% of those allergic reactions happened within 15 minutes of vaccination and mostly (81%) among people with a documented history of allergies or allergic reactions.[161] The UK's Medicines and Healthcare products Regulatory Agency (MHRA) advised on 9 December 2020 that people who have a history of "significant" allergic reaction should not receive the Pfizer–BioNTech COVID‑19 vaccine.[163][164][165] On 12 December, the Canadian regulator followed suit, noting that: "Both individuals in the U.K. had a history of severe allergic reactions and carried adrenaline auto injectors. They both were treated and have recovered."[100]

The European Medicines Agency (EMA) regularly reviews the data on the vaccine's safety.[6] In a report published on 4 March 2021, it concluded that "the benefits of Comirnaty in preventing COVID‑19 continue to outweigh any risks, and there are no recommended changes regarding the use of this vaccine."[6] The EMA added skin rash and pruritus (itching of the skin) as uncommon side effects (occurring in fewer than 1 in 100 persons), and urticaria (raised, red and itchy skin rash) and angioedema (rapid swelling under the skin) as rare side effects (occurring in fewer than 1 in 1,000 persons) in April 2021.[6][166]

According to Israel's Ministry of Health there is a probable relationship between the second dose and mild myocarditis in a small group of 16-30 year-old men. Between December 2020 and May 2021, there were 275 cases of myocarditis in a group of 5 million people vaccinated, 95% of which were classified as mild.[167]

Manufacturing

File:Pfizer-BioNTech COVID-19 vaccine (2020) E.jpg
A US soldier holding the Pfizer–BioNTech vaccine

Pfizer and BioNTech are manufacturing the vaccine in their own facilities in the United States and in Europe. The license to distribute and manufacture in China was purchased by Fosun, alongside its investment in BioNTech.[23][24]

Manufacturing the vaccine requires a three-stage process. The first stage involves the molecular cloning of DNA plasmids that code for the spike protein by infusing them into Escherichia coli bacteria. For all markets, this stage is conducted in the United States,[168] at a small Pfizer pilot plant in Chesterfield, Missouri[169][170] (near St. Louis). After four days of growth, the bacteria are killed and broken open, and the contents of their cells are purified over a week and a half to recover the desired DNA product. The DNA is bottled and frozen for shipment. Safely and quickly transporting the DNA at this stage is so important that Pfizer has used its company jet and helicopter to assist.[171]

The second stage is being conducted at a Pfizer plant in Andover, Massachusetts,[172] in the United States, and at BioNTech's plants in Germany.[168] The DNA is used as a template to build the desired mRNA strands,[171] which takes about four days.[168] Once the mRNA has been created and purified, it is frozen in plastic bags about the size of a large shopping bag, of which each can hold up to 10 million doses. The bags are placed on trucks which take them to the next plant.[171]

File:A Pfizer employee putting dry ice in a box to protect the COVID-19 vaccines during transport.jpg
A Pfizer employee putting dry ice in a box to protect the COVID-19 vaccines during transport at the Puurs factory
File:Boxes containing the COVID-19 vaccines.jpg
Boxes containing the COVID-19 vaccines at the Pfizer factory in Puurs
File:Inside view of the Pfizer factory.jpg
Inside view of freezers at the Pfizer factory in Puurs

The third stage is being conducted at Pfizer plants in Portage, Michigan[173] (near Kalamazoo) in the United States, and Puurs in Belgium. This stage involves combining the mRNA with lipid nanoparticles, then filling vials, boxing vials, and freezing them.[171] Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids.[174] As of November 2020, the major bottleneck in the manufacturing process was combining mRNA with lipid nanoparticles.[171] At this stage, it takes only four days to go from mRNA and lipids to finished vials, but each lot must then spend several weeks in deep-freeze storage while undergoing verification against 40 quality-control measures.[168]

Before May 2021,[175] the Pfizer plant in Puurs was responsible for all vials for destinations outside the United States.[168] Therefore, all doses administered in the Americas outside of the United States before that point in time required at least two transatlantic flights (one to take DNA to Europe and one to bring back finished vaccine vials).[168]

In February 2021, Pfizer revealed that the entire sequence initially took about 110 days on average from start to finish, and that the company was making progress on reducing the time to 60 days.[176] More than half the days in the production process are dedicated to rigorous testing and quality assurance at each of the three stages.[176] Pfizer also revealed that the process requires 280 components and relies upon 25 suppliers located in 19 different countries.[168]

Vaccine manufacturers normally take several years to optimize the process of making a particular vaccine for speed and cost-effectiveness before attempting large-scale production.[176] Due to the urgency presented by the COVID‑19 pandemic, Pfizer and BioNTech began production immediately with the process by which the vaccine had been originally formulated in the laboratory, then started to identify ways to safely speed up and scale up that process.[176]

File:Impfzentrum Ilsfeld-Auenstein, 2021 (14).jpg
Tips with tozinameran in a vaccination center

BioNTech announced in September 2020, that it had signed an agreement to acquire a manufacturing facility in Marburg, Germany, from Novartis to expand their vaccine production capacity.[177] Once fully operational, the facility would produce up to 750 million doses per year, or more than 60 million doses per month. The site will be the third BioNTech facility in Europe which produces the vaccine, while Pfizer operates at least four production sites in the United States and Europe.[177]

The Marburg facility had previously specialized in cancer immunotherapy for Novartis.[178] By the end of March 2021, BioNTech had finished retrofitting the facility for mRNA vaccine production and retraining its 300 staff, and obtained approval to begin manufacturing.[178] Besides making mRNA, the Marburg facility also performs the step of combining mRNA with lipids to form lipid nanoparticles, then ships the vaccine in bulk to other facilities for fill and finish (i.e., filling and boxing vials).[178]

On 23 April 2021 the EMA authorised an increase in batch size and associated process scale up at Pfizer's plant in Puurs. This increase is expected to have a significant impact on the supply of the vaccine in the European Union.[179][180]

At the end of April 2021, it was reported that Pfizer had started to export vaccine doses to Mexico and Canada from the Kalamazoo plant, which is much closer geographically to both countries than the Puurs plant.[175]

Logistics

The vaccine is delivered in vials that, once diluted, contain 2.25 ml of vaccine (0.45 ml frozen plus 1.8 ml diluent).[89] According to the vial labels, each vial contains five 0.3 ml doses, however excess vaccine may be used for one, or possibly two, additional doses.[89][149] The use of low dead space syringes to obtain the additional doses is preferable, and partial doses within a vial should be discarded.[89][181] The Italian Medicines Agency officially authorized the use of excess doses remaining within single vials.[182] The Danish Health Authority allows mixing partial doses from two vials.[183] As of 8 January 2021, each vial contains six doses.[101][184][185][181] In the United States, vials will be counted as five doses when accompanied by regular syringes and as six doses when accompanied by low dead space syringes.[186]

File:Ultracold storage (cropped).jpg
The Pfizer–BioNTech vaccine must be kept at extremely low temperatures to ensure effectiveness, roughly between −80 and −60 °C (−112 and −76 °F)

The vaccine needs to be stored at temperatures between −80 and −60 °C (−112 and −76 °F),[52] until 30 days before vaccination[187] when it can be stored at 2 to 8 °C (36 to 46 °F), and up to two hours at temperatures up to 25 °C (77 °F)[7][10] or 30 °C (86 °F).[188][189] In February 2021, the U.S. Food and Drug Administration (FDA) updated the emergency use authorization (EUA) to permit undiluted frozen vials of the vaccine to be transported and stored at between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use.[89][190][191]

Even high-income countries have limited cold chain capacity for ultracold transport and storage of a vaccine that degrades within five days when thawed, and requires two shots three weeks apart.[51] The vaccine needs to be stored and transported at ultracold temperatures between −80 and −60 °C (−112 and −76 °F),[52][79][51][192][193] much lower than for the similar Moderna vaccine. The head of Indonesia's Bio Farma Honesti Basyir said purchasing the vaccine is out of the question for the world's fourth-most populous country, given that it did not have the necessary cold chain capability. Similarly, India's existing cold chain network can handle only temperatures between 2 and 8 °C (36 and 46 °F), far above the requirements of the vaccine.[194][195]

Advance orders

Pfizer indicated in its 9 November press release that 50 million doses could be available by the end of 2020, with about 1.3 billion doses provided globally by 2021.[34] In February 2021, BioNTech announced it would increase production by more than 50% to manufacture 2 billion doses in 2021,[196] raised again at the end of March to 2.5 billion doses in 2021.[49]

In July 2020, the vaccine development program Operation Warp Speed placed an advance order of US$1.95 billion with Pfizer to manufacture 100 million doses of a COVID‑19 vaccine for use in the United States if the vaccine was shown to be safe and effective.[23][197][198][199] By mid-December 2020, Pfizer had agreements to supply 300 million doses to the European Union,[200] 120 million doses to Japan,[201] 40 million doses (10 million before 2021) to the United Kingdom,[79] 20 million doses to Canada,[202] an unspecified number of doses to Singapore,[203] and 34.4 million doses to Mexico.[204] Fosun also has agreements to supply 10 million doses to Hong Kong and Macau.[205] The Hong Kong government said it would receive its first batch of 1 million doses by the first quarter of 2021.[206]

BioNTech and Fosun agreed to supply China with a batch of 100 million doses in 2021, subject to regulatory approval.[26][207] The initial supply will be delivered from BioNTech's production facilities in Germany.[26][207]

In January 2021, Pfizer and BioNTech offered to supply 50 million doses of COVID‑19 vaccine for health workers across Africa between March and the end of 2021, at a discounted price of US$10 per dose.[208] In response South Africa has secured 20 million doses expected to be delivered in consignments after March.[209]

On 23 April 2021, the European Union announced a third contract with Pfizer-BioNTech for up to 1.8 billion doses of the companies' mRNA vaccine for distribution within two years.[210]

On 6 May 2021, the International Olympic Committee purchased doses from Pfizer-BioNTech to help immunize volunteers, staff, and participating athletes during the 2020 Summer Olympics which will take place in July 2021 in Tokyo.[211] President Joe Biden's administration pledged on 9 June 2021 to distribute 500 million doses of the Pfizer-BioNTech vaccine among approximately 100 countries over the course of the upcoming year.[212]

Society and culture

Name

BNT162b2 was the code name during development and testing,[31][213] tozinameran is the recommended international nonproprietary name (INN),[214] and Comirnaty is the brand name.[13][6] According to BioNTech, the name Comirnaty "represents a combination of the terms COVID‑19, mRNA, community, and immunity".[18][215]

The vaccine also has the common name "COVID‑19 mRNA vaccine (nucleoside-modified)"[6] and may be distributed in packaging with the name "Pfizer–BioNTech COVID‑19 Vaccine" in the US.[17]

Economics

Pfizer reported revenue of US$154 million from the BNT162b2 vaccine in 2020.[66]

In popular culture

<templatestyles src="Module:Hatnote/styles.css"></templatestyles>

See also: COVID-19 misinformation

Videos on video-sharing platforms circulated around May 2021 showing people having magnets stick to their arms after receiving the vaccine, purportedly demonstrating the conspiracy theory that vaccines contain microchips, but these videos have been debunked.[216][217][218][219][220]

Notes

  1. ↑ 1.0 1.1 According to the British National Formulary and MedDRA conventions, side effects are "very common" when they occur in more than 1 in 10 instances; "common", 1 in 100 to 1 in 10; "uncommon", 1 in 1,000 to 1 in 100; "rare", 1 in 10,000 to 1 in 1,000; and "very rare" when they occur in less than 1 in 10,000 instances.[40]

References

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Further reading

  • Lua error in package.lua at line 80: module 'strict' not found.

External links

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