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Wikipedia

Pfizer–BioNTech COVID-19 vaccine

January 01, 1970

"Pfizer vaccine" and "BioNTech vaccine" redirect here. For the manufacturers, see Pfizer and BioNTech.

The Pfizer–BioNTech COVID-19 vaccine, sold under the brand name Comirnaty,[2][32] is an mRNA-based COVID-19 vaccine developed by the German biotechnology company BioNTech. For its development, BioNTech collaborated with the American company Pfizer to carry out clinical trials, logistics, and manufacturing.[44][45] It is authorized for use in humans to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus.[2][30] The vaccine is given by intramuscular injection.[34] It is composed of nucleoside-modified mRNA (modRNA) that encodes a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles.[46] Initial guidance recommended a two-dose regimen, given 21 days apart;[34][47][48][49] this interval was subsequently extended to up to 42 days in the United States,[34][50] and up to four months in Canada.[51][52]

Pfizer–BioNTech COVID-19 vaccine
A vial of the Pfizer–BioNTech COVID‑19 vaccine for the U.S. market
Vaccine description
TargetSARS-CoV-2
Vaccine typemRNA
Clinical data
Trade namesComirnaty[1][2][3]
Other namesBNT162b2, COVID-19 mRNA vaccine (nucleoside-modified), COVID-19 Vaccine (mRNA)[4]
AHFS/Drugs.comMonograph
MedlinePlusa621003
License data
  • EU EMA: by INN
  • US DailyMed: Pfizer-BioNTech COVID-19 vaccine
Pregnancy
category
Routes of
administration		Intramuscular
ATC code
Legal status
Legal status

ZA: Section 21[42][43]

Full list of Pfizer-BioNTech vaccine authorizations
Identifiers
CAS Number
  • 2417899-77-3
PubChem SID
  • 434370509
DrugBank
  • DB15696
UNII
  • 5085ZFP6SJ
KEGG
  • D11971
ChEMBL
  • ChEMBL4650429

Clinical trials began in April 2020;[47] by November 2020, the vaccine had entered phase III clinical trials, with over 40,000 people participating.[53] Interim analysis of study data showed a potential efficacy of 91.3% in preventing symptomatic infection within seven days of a second dose and no serious safety concerns.[49][54] Most side effects are mild to moderate in severity and resolve within a few days.[2][55] Common side effects include mild to moderate pain at the injection site, fatigue, and headaches.[56][57] Reports of serious side effects, such as allergic reactions, remain very rare[a] with no long-term complications documented.[2][59]

The vaccine is the first COVID‑19 vaccine to be authorized by a stringent regulatory authority for emergency use[60][61] and the first to be approved for regular use.[41] In December 2020, the United Kingdom was the first country to authorize its use on an emergency basis.[59] It is authorized for use at some level in the majority of countries.[62][63][64][65] On 23 August 2021, the Pfizer–BioNTech vaccine became the first COVID-19 vaccine to be approved in the US by the Food and Drug Administration (FDA).[29][32][66] The logistics of distributing and storing the vaccine present significant challenges due to the requirement for its storage at extremely low temperatures.[67]

In August 2022, a bivalent version of the vaccine (Pfizer-BioNTech COVID-19 Vaccine, Bivalent) was authorized for use as a booster dose in individuals aged twelve and older in the US.[68][69][70][71] The following month, the BA.1 version of the bivalent vaccine (Comirnaty Original/Omicron BA.1 or tozinameran/riltozinameran)[72] was authorized as a booster for use in the UK.[73][74][75] The same month, the European Union authorized both the BA.1 and the BA.4/BA.5 (tozinameran/famtozinameran) booster versions of the bivalent vaccine.[2][3][40]

Medical uses

The Pfizer–BioNTech COVID-19 vaccine is used to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus, by eliciting an immune response to the S antigen.[1][2][30][39] The vaccine is used to reduce morbidity and mortality from COVID-19.[34]

The vaccine is supplied in a multidose vial as "a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection".[30][39][76] It must be thawed to room temperature and diluted with normal saline before administration.[39][76]

The initial course consists of two doses.[34][39] The World Health Organization (WHO) recommends an interval of three to four weeks between doses. Delaying the second dose by up to twelve weeks increases immunogenicity, even in older adults, against all variants of concern.[77] Authors of the Pitch study think that the optimal interval against the Delta variant is around eight weeks, with longer intervals leaving receptors vulnerable between doses.[77]

A third, fourth, or fifth dose can be added in some countries.[68][78][79][80][81][82]

Effectiveness

A test-negative[note 1] case-control study published in August 2021, found that two doses of the BNT162b2 (Pfizer) vaccine had 93.7% effectiveness against symptomatic disease caused by the alpha (B.1.1.7) variant and 88.0% effectiveness against symptomatic disease caused by the delta (B.1.617.2) variant.[83] Notably, effectiveness after one dose of the Pfizer vaccine was 48.7% against alpha and 30.7% against delta, similar to effectiveness provided by one dose of the ChAdOx1 nCoV-19 vaccine.[84]

On 27 August, the U.S. Centers for Disease Control and Prevention (CDC) published a study reporting that the effectiveness against infection decreased from 91% (81–96%) to 66% (26–84%) when the Delta variant became predominant in the US, which may be due to unmeasured and residual confounding related to a decline in vaccine effectiveness over time.[85]

Unless indicated otherwise, the following effectiveness ratings are indicative of clinical effectiveness two weeks after the second dose. A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval.[86] Effectiveness is generally expected to slowly decrease over time.[87]

Initial effectiveness by variant
Doses Severity of illness Alpha Beta Gamma Delta Omicron Others circulating previously[A]
1 Asymptomatic 38% (29–45%)[89] 17% (10–23%)[90] Not reported 30% (17–41%)[89] Not reported 60% (53–66%)
Symptomatic 27% (13–39%)[89] 43% (22–59%)[91] 33% (15–47%)[89] Not reported 66% (57–73%)
Hospitalization 83% (62–93%)[B] 0% (0–19%)[90] 56% (−9 to 82%)[91] 94% (46–99%)[B] Not reported 78% (61–91%)
2 Asymptomatic 92% (90–93%)[89] 75% (71–79%)[90] Not reported 79% (75–82%)[89] Not reported 92% (88–95%)
Symptomatic 92% (88–94%)[89] 88% (61–96%)[91] 83% (78–87%)[89] 88% (66–96%)[C] 94% (87–98%)
Hospitalization 95% (78–99%)[B] 100% (74–100%)[90] 100%[D][91] 96% (86–99%)[B] 70% (62–76%)[95] 87% (55–100%)
3[E] Symptomatic Not reported Not reported Not reported 96% (89–99%)[F] 76% (56–86%)[G] Not reported
  1. ^ Surveillance study from 20 December 2020 to 1 February 2021 in Israel.[88] During this period, according to Nextstrain, the dominant variant in Israel was lineage B.1.1.50 and the Alpha variant was becoming dominant.
  2. ^ a b c d Preliminary data of effectiveness against hospitalization referenced by Public Health England.[92][93]
  3. ^ Effectiveness drops to 49% (24–65%) in weeks 10–14 after the second dose and then stabilizes at 34%–37% thereafter.[94]
  4. ^ A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
  5. ^ Booster dose.
  6. ^ Efficacy data from a study with more than 10,000 participants.[96]
  7. ^ Effectiveness drops to about 45% 10 weeks after the booster dose.[97][94]


On 12 November, Public Health England reported a possible but extremely small reduction in effectiveness against symptomatic disease from the Delta sublineage AY.4.2 at longer intervals after the second dose.[98]

Preliminary data suggest that the effectiveness against the Omicron variant starts to decline in about 10 weeks, either after the initial two-dose regimen or after the booster dose.[94][97] For other variants, the effectiveness of the initial doses starts to decline in about six months.[99] A case-control study in Qatar from 1 January to 5 September 2021 found that effectiveness against infection peaked at 78% (95% CI, 76–79%) in the first month after the second dose, followed by a slow decline that accelerated after the fourth month, reaching 20% at months 5 to 7. A similar trajectory was observed against symptomatic disease and against specific variants. Effectiveness against severe disease, hospitalization and death was more robust, peaking at 96% (93–98%) in the second month and remaining almost stable through the sixth month, declining thereafter.[100]

On 21 October, a phase 3 trial showed that a booster dose given approximately 11 months after the second dose restored the protective effect to the 96% (95% CI, 89–99%) efficacy level against symptomatic disease from the Delta variant.[101][96]

On 8 December, Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide a similar level of neutralizing antibodies against the Omicron variant as seen after two doses against other variants.[102]

On 14 December, private health insurer Discovery Health, in collaboration with the South African Medical Research Council, reported that real-world data from more than 211,000 cases of COVID-19 in South Africa, of which 78,000 were of the Omicron variant, indicate that effectiveness against the variant after two doses is about 70% against hospital admission and 33% against symptomatic disease. Protection against hospital admission is maintained for all ages and groups with comorbidities.[103]

A study of the bivalent booster effectiveness against severe COVID-19 outcomes in Finland, September 2022–January 2023, has shown that it reduced the risk of severe COVID-19 outcomes among the elderly. By contrast, among the chronically-ill 18–64-year-olds the risk was similar among those who received bivalent vaccine and those who did not. Among the elderly a bivalent booster provided highest protection during the first two months after vaccination, but thereafter signs of waning were observed. The effectiveness among individuals aged 65–79 years and those aged 80 years or more was similar.[104]

Specific populations

Based on the results of a preliminary study, the U.S. Centers for Disease Control and Prevention (CDC) recommends that pregnant women get vaccinated with the COVID‑19 vaccine.[105][106]

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 children aged between 12 and 15 years.[107][108]

On 19 May 2021, experts commissioned by the Norwegian Medicines Agency concluded that the Pfizer-BioNTech vaccine is the likely cause of ten deaths of frail elderly patients in Norwegian nursing homes. They said that people with very short life expectancies have little to gain from vaccination, having a real risk of adverse reactions in the last days of life and of dying earlier.[109]

A 2021 report by the New South Wales Government (NSW Health) in Australia found that the Pfizer-BioNTech vaccine is safe for those with 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 with cancer, inflammatory bowel disease and various liver diseases be prioritised in the vaccination schedules over other patients that do not have said conditions.[110]

On 20 September 2021, Pfizer announced that a clinical trial conducted in more than 2,200 children aged 5–11 has generated a "robust" response and is safe.[111][112]

Adverse effects

See also: Vaccine adverse event

In Phase III trials for the vaccine, there were no safety concerns and few adverse events.[49][54]

Most side effects of the Pfizer–BioNTech COVID‑19 vaccine are mild to moderate in severity, and are gone within a few days.[55][2] They are similar to other adult vaccines and are normal signs that the body is building protection to the virus.[55] During clinical trials, the common side effects affecting more than one in 10 people are (in order of frequency): pain and swelling at the injection site, tiredness, headache, muscle aches, chills, joint pain, fever or diarrhea.[113] Fever is more common after the second dose.[113]

The European Medicines Agency (EMA) regularly reviews the data on the vaccine's safety. The safety report published on 8 September 2021 by the EMA was based on over 392 million doses administered in the European Union.[2] According to the EMA "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."[2] Rare side effects (that may affect up to one in 1,000 people) include temporary one sided facial drooping and allergic reactions, such as hives or swelling of the face.[2]

Allergy

Documented hypersensitivity to polyethylene glycol (PEG) (a very rare allergy) is listed as a contraindication to the COVID-19 Pfizer vaccine.[114] Severe allergic reaction has been observed in approximately eleven cases per million doses of vaccine administered.[115][116] 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.[115] 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.[117][118][119] 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."[120]

Myocarditis

In June 2021, the Israel's Ministry of Health announced a probable relationship between the second dose and myocarditis in a small group of 16–30-year-old men.[121] Between December 2020 and May 2021, there were 55 cases of myocarditis per 1 million people vaccinated, 95% of which were classified as mild and most spent no more than four days in the hospital.[121] Since April 2021, increasing number of cases of myocarditis and pericarditis have been reported in the United States in about 13 per 1 million young people, mostly male and over the age of 16, after vaccination with the Pfizer–BioNTech or the Moderna vaccine.[122][123] Most affected individuals recover quickly with adequate treatment and rest.[124] Since February 2022, the German Standing Committee on Vaccination recommends aspiration for COVID-19 vaccination as precautionary measure.[125]

Pharmacology

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,[126] triggering an immune response against infection by the virus protein.[127]

Sequence

The modRNA sequence of the vaccine is 4,284 nucleotides long.[128] 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;[46][129] 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[130] and a poly(A) tail comprising 30 adenosine residues, a 10-nucleotide linker sequence, and 70 other adenosine residues (bases 4175–4284).[128] The sequence contains no uridine residues; they are replaced by 1-methyl-3'-pseudouridylyl.[128] The 2P proline substitutions in the spike proteins were originally developed for a Middle East respiratory syndrome (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).[129]

Chemistry

In addition to the mRNA molecule, the vaccine contains the following inactive ingredients (excipients):[26][120][113]

The first four of these are lipids. The lipids and modRNA together form nanoparticles that act not only as carriers to get the modRNA into the human cells, but also as adjuvants.[131] ALC-0159 is a polyethylene glycol conjugate, i.e., a PEGylated lipid.[132]

Manufacturing

 
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 the vaccine in China was purchased by Fosun, alongside its investment in BioNTech.[45][133]

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,[134] at a small Pfizer pilot plant in Chesterfield, Missouri[135][136] (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.[137]

The second stage is being conducted at a Pfizer plant in Andover, Massachusetts,[138] in the United States, and at BioNTech's plants in Germany.[134] The DNA is used as a template to build the desired mRNA strands,[137] which takes about four days.[134] 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.[137]

 
A Pfizer employee putting dry ice in a box to protect the COVID-19 vaccines during transport at the Puurs factory
 
Boxes containing the COVID‑19 vaccines at the Pfizer factory in Puurs
 
Inside view of Pfizer factory in Puurs
External videos
  Loading dock operations at Pfizer's Portage, Michigan facility, December 13, 2020, C-SPAN
  President Joe Biden and Michigan Gov. Gretchen Whitmer tour the Portage, Michigan Pfizer facility with Pfizer CEO Albert Bourla, February 19, 2021, C-SPAN

The third stage is being conducted at Pfizer plants in Portage, Michigan[139] (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.[137] Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids.[140] As of November 2020, the major bottleneck in the manufacturing process is combining mRNA with lipid nanoparticles.[137] 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.[134]

Before May 2021,[141] the Pfizer plant in Puurs was responsible for all vials for destinations outside the United States.[134] 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).[134]

In February 2021, BioNTech announced it would increase production by more than 50% to manufacture 2 billion doses in 2021,[142] raised again at the end of March to 2.5 billion doses in 2021.[143]

In February 2021, Pfizer revealed that the entire sequence initially took about 110 days on average from start to finish, and that the company is making progress on reducing the time to 60 days.[144] More than half the days in the production process are dedicated to rigorous testing and quality assurance at each of the three stages.[144] Pfizer also revealed that the process requires 280 components and relies upon 25 suppliers located in 19 countries.[134]

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.[144] 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.[144]

 
Syringes containing Pfizer COVID-19 vaccine doses

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.[145] 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 that produces the vaccine, while Pfizer operates at least four production sites in the United States and Europe.[145]

The Marburg facility had previously specialized in cancer immunotherapy for Novartis.[146] 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.[146] 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).[146]

On 23 April 2021, the EMA authorized 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.[147][148]

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.[141]

Logistics

The vaccine is delivered in vials that, once diluted, contain 2.25 mL of vaccine, comprising 0.45 mL frozen and 1.8 mL diluent.[149] 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.[149][150] The use of low dead space syringes to obtain the additional doses is preferable, and partial doses within a vial should be discarded.[149][151] The Italian Medicines Agency officially authorized the use of excess doses remaining within single vials.[152] The Danish Health Authority allows mixing partial doses from two vials.[153] As of 8 January 2021, each vial contains six doses.[113][154][155][151] 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.[156]

 
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 can be stored at 2 to 8 °C (36 to 46 °F) for thirty days before use[157][158] and at 25 °C (77 °F)[26][30] or 30 °C (86 °F) [159][8] for up to two hours before use. During distribution the vaccine is stored in special containers that maintain temperatures between −80 and −60 °C (−112 and −76 °F).[160]

Low-income countries have limited cold chain capacity for ultracold transport and storage of a vaccine.[161] The necessary storage temperatures for the vaccine[160][162][161][163][164] are 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.[165][166]

History

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.[167] The SARS-CoV-2 virus, which causes COVID‑19, was detected in December 2019,[168] 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 triggering an urgent international response to prepare for an outbreak and hasten development of preventive vaccines.[169][170]

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.[171] BioNTech started its program 'Project Lightspeed' to develop a vaccine against the new COVID‑19 virus based on its already established mRNA-technology,[53] which they had been developing since leading mRNA researcher Katalin Karikó joined the company in 2013.[172] 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.[173]

Meanwhile, since 2018, Pfizer had been working with BioNTech on developing a mRNA vaccine for influenza, but the chief executive officers of the two companies did not become personally acquainted until COVID-19 came along.[174] After a few phone calls, Pfizer CEO Albert Bourla and Şahin agreed that their companies would work together on the development of BioNTech's COVID-19 vaccine.[174] The two agreed to begin work immediately, with no formal written legal agreement in place to govern the new collaboration.[174] BioNTech transferred its know-how to Pfizer the next day.[174] A letter of intent was signed three weeks later, and the formal commercial agreement between Pfizer and BioNTech for the COVID-19 vaccine was signed in January 2021.[174]

Funding

According to Pfizer, research and development for the vaccine cost close to US$1 billion.[175]

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.[176][133]

In April 2020, BioNTech signed a partnership with Pfizer and received $185 million, including an equity investment of approximately $113 million.[177][178][179]

In June 2020, BioNTech received €100 million (US$119 million) in financing from the European Commission and European Investment Bank.[180] The Bank's deal with BioNTech started early in the pandemic, when the Bank's staff reviewed its portfolio and came up with BioNTech as one of the companies capable of developing a COVID‑19 vaccine. The European Investment Bank had already signed a first transaction with BioNTech in 2019.[181]

In September 2020, the German government granted BioNTech €375 million (US$445 million) for its COVID‑19 vaccine development program.[182]

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.[183]

Clinical trials

See also: COVID-19 vaccine clinical research § Trial and authorization status

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.[47][53] The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech.[127] 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.[184][46][185][186]

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.[46] During the same month, the European Medicines Agency (EMA) began a periodic review of BNT162b2.[187]

The study of BNT162b2 is a continuous-phase trial in phase III as of November 2020.[47] It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals".[47] 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.[49][133]

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.[47] The Phase III results indicating a 95% efficacy of the developed vaccine were published on 18 November 2020.[53] For approval in the EU, an overall vaccine efficacy of 95% was confirmed by the EMA.[188] The EMA clarified that the second dose should be administered three weeks after the first dose.[189]

 
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)[190]

At 14 days after dose 1, the cumulative incidence begins to diverge between the vaccinated group and the placebo group. The highest concentration of neutralizing antibodies is reached 7 days after dose 2 in younger adults and 14 days after dose 2 in older adults.[188]

Vaccine efficacy against confirmed symptomatic COVID‑19[188]
Endpoint subgroup Efficacy (95% confidence interval)
All ages 95.0% (90.0–97.9%)
Age 12–17 Not estimable[b]
Age 18–64 95.1% (89.6–98.1%)
Age 65–74 92.9% (53.1–99.8%)
Age ≥75 100.0% (−13.1 to 100.0%)
All ages, after dose 1, before dose 2 52.4% (29.5–68.4%)
All ages, ≥10 days after dose 1, before dose 2 86.7% (68.6–95.4%)
All ages, <7 days after dose 2 90.5% (61.0–98.9%)
All ages, ≥7 days after dose 2 94.8% (89.8–97.6%)
All ages, USA 94.9% (88.6–98.2%)
All ages, Argentina 97.2% (83.3–99.9%)
All ages, Brazil 87.7% (8.1–99.7%)

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.[49][191][162]

High antibody activity persists for at least three months after the second dose, with an estimated antibody half-life of 55 days. From these data, one study suggested that antibodies might remain detectable for around 554 days.[192]

Specific populations

Pfizer and BioNTech started a Phase II–III randomized control trial in healthy pregnant women 18 years of age and older (NCT04754594).[193] The study will evaluate 30 mcg 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.[194]

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.[195]

In January 2021, Pfizer said it had finished enrolling 2,259 children aged between 12 and 15 years to study the vaccine's safety and efficacy.[196] 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.[197]

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.[198]

On 2 November 2021, The BMJ published a piece by journalist Paul D. Thacker alleging there has been "poor practice" at Ventavia, one of the companies involved in the phase III evaluation trials of the Pfizer vaccine.[199] The report was enthusiastically embraced by anti-vaccination activists. David Gorski commented in Science-Based Medicine that Thacker's article presented facts without necessary context to misleading effect, playing up the seriousness of the noted problems.[200]

Authorizations

  Full authorization
  Emergency authorization
  Eligible COVAX recipient
See also: List of COVID-19 vaccine authorizations § Pfizer–BioNTech

Although jointly developed with Pfizer,[201] Comirnaty is based on BioNTech's proprietary mRNA technology,[201] and BioNTech holds the Marketing Authorization in the United States, the European Union, the UK, and Canada;[201] expedited licenses such as the US emergency use authorization (EUA) are held jointly with Pfizer in many countries.[201]

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.[60] It is the first COVID‑19 vaccine to be approved for national use after undergoing large scale trials,[202] and the first mRNA vaccine to be authorized for use in humans.[60][203] The United Kingdom thus became the first Western country to approve a COVID‑19 vaccine for national use,[204] although the decision to fast-track the vaccine was criticized by some experts.[205]

After the United Kingdom, the following countries and regions expedited processes to approve the Pfizer–BioNTech COVID‑19 vaccine for use: Argentina,[206] Australia,[207] Bahrain,[208] Canada,[209][210] Chile,[211] Costa Rica,[212] Ecuador,[211] Hong Kong,[213] Iraq,[214] Israel,[215] Jordan,[216] Kuwait,[217] Malaysia,[218] Mexico,[219][220] Oman,[221] Panama,[222] the Philippines,[223] Qatar,[224] Saudi Arabia,[225][226][227] Singapore,[228][229][230] South Korea,[231][232] the United Arab Emirates,[233] the United States,[234] and Vietnam.[235]

The World Health Organization (WHO) authorized it for emergency use.[236][237][238][239]

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 Food and Drug Administration (FDA).[240] Pfizer applied for an EUA on 20 November 2020,[241] and the FDA approved the application three weeks later on 11 December 2020. The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) approved recommendations for vaccination of those aged sixteen years or older.[242][243] Following the EUA issuance, BioNTech and Pfizer continued the Phase III clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) of the vaccine in the United States.[240][33][149] On 10 May 2021, the US FDA also authorized the vaccine for people aged 12 to 15 under an expanded EUA.[244][33][149][245][150] The FDA recommendation was endorsed by the ACIP and adopted by the CDC on 12 May 2021.[246][247] In October 2021, the EUA was expanded to include children aged 5 through 11 years of age.[248] In June 2022, the EUA was expanded to include children aged six months through four years of age.[31]

On 16 February 2021, the South African Health Products Regulatory Authority (SAHPRA) in South Africa issued Section 21, Emergency Use Approval for the vaccine.[249][250]

On 5 May 2021, Health Canada authorized the vaccine for people aged 12 to 15.[251][252] On 18 May 2021, Singapore's Health Sciences Authority authorized the vaccine for people aged 12 to 15.[253] The European Medicines Agency (EMA) followed suit on 28 May 2021.[254]

On 4 June 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) came to a similar decision and approved the use of the vaccine for people twelve years of age and older.[26][107][108]

Standard

On 19 December 2020, the Swiss Agency for Therapeutic Products (Swissmedic) granted temporary authorization for 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.[41][255][256][257][258][259][260] This is the first authorization under a standard procedure.[41][255]

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.[2][261][3] The recommendation was accepted by the European Commission the same day.[261][262]

On 23 February 2021, the Brazilian Health Regulatory Agency approved the Pfizer–BioNTech COVID‑19 vaccine under its standard marketing authorization procedure.[263][264][265][266] In June 2021, the approval was extended to those aged twelve or over.[267][268] Pfizer's negotiation process with Brazil (and other Latin American countries) was described as "bullying". The contract prohibits the state of Brazil from publicly discussing the existence or the terms of their agreement with Pfizer–BioNTech without the former's written consent. Brazil was also restricted from donating or receiving donations of vaccines.[269][270]

In July 2021, the U.S. Food and Drug Administration (FDA) granted priority review designation for the biologics license application (BLA) for the Pfizer–BioNTech COVID-19 vaccine with a goal date for the decision in January 2022.[271][272] On 23 August 2021, the FDA approved the vaccine for use for those aged sixteen years and older.[32][66][29]

The Pfizer-BioNTech Comirnaty COVID-19 vaccine was authorized in Canada in September 2021, for people aged twelve and older.[20][21][19][273]

In July 2022, the FDA approved the vaccine for use for those aged twelve years and older.[274][29]

In September 2022, the CHMP of the EMA recommended converting the conditional marketing authorizations of the vaccine into standard marketing authorizations.[40] The recommendation covers all existing and upcoming adapted Comirnaty vaccines, including the adapted Comirnaty Original/Omicron BA.1 (tozinameran/riltozinameran) and Comirnaty Original/Omicron BA.4/5 (tozinameran/famtozinameran).[2][40]

Further development

Homologous prime-boost vaccination

See also: COVID-19 vaccine clinical research § Homologous prime-boost vaccination

In July 2021, Israel's Prime Minister announced that the country was rolling out a third dose of the Pfizer-BioNTech vaccine to people over the age of 60, based on data that suggested significant waning immunity from infection over time for those with two doses.[275] The country expanded the availability to all Israelis over the age of 12, after five months since their second shot. On 29 August 2021, Israel's coronavirus czar announced that Israelis who had not received a booster shot within six months of their second dose would lose access to the country's green pass vaccine passport.[276] Studies performed in Israel found that a third dose reduced the incidence of serious illness.[277]

In August 2021, the United States Department of Health and Human Services (HHS) announced a plan to offer a booster dose eight months after the second dose, citing evidence of reduced protection against mild and moderate disease and the possibility of reduced protection against severe disease, hospitalization, and death.[278] The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) authorized the use of an additional mRNA vaccine dose for immunocompromised individuals at that time.[78][79] Scientists and the WHO noted in August 2021, the lack of evidence on the need for a booster dose for healthy people and that the vaccine remains effective against severe disease months after administration.[279] In a statement, the WHO and Strategic Advisory Group of Experts (SAGE) said that, while protection against infection may be diminished, protection against severe disease will likely be retained due to cell-mediated immunity.[280] Research into optimal timing for boosters is ongoing, and a booster too early may lead to less robust protection.[281]

In September 2021, the FDA and CDC authorizations were extended to provide a third shot for other specific groups.[282][283][284]

In October 2021, the European Medicines Agency (EMA) stated that a booster shot of the vaccine could be given to healthy people, aged 18 years and older, at least six months after their second dose.[80] It also stated that people with "severely weakened" immune systems can receive an extra dose of either the Pfizer-BioNTech vaccine or the Moderna vaccine starting at least 28 days after their second dose.[80] The final approval to provide booster shots in the European Union will be decided by each national government.[285]

In October 2021, the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses.[286][287][288]

In October 2021, the Australian Therapeutic Goods Administration (TGA) provisionally approved a booster dose of Comirnaty for people 18 years of age and older.[289][290]

In January 2022, the FDA expanded the emergency use authorization to provide for the use of a vaccine booster dose to those aged 12 through 15 years of age, and it shortened the waiting period after primary vaccination to five months from six months.[291][292][293][294]

In May 2022, the FDA expanded the emergency use authorization to provide for the use of a vaccine booster dose to those aged 5 through 11 years of age.[295]

In August 2022, the FDA revoked the emergency use authorization for the monovalent vaccine booster for people aged twelve years of age and older and replaced it with an emergency use authorization for the bivalent vaccine booster dose for the same age group.[68]

Heterologous prime-boost vaccination

For use as a heterologous booster dose, see Oxford–AstraZeneca COVID-19 vaccine § Heterologous prime-boost vaccination.
See also: COVID-19 vaccine clinical research § Heterologous prime-boost vaccination

In October 2021, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) authorized the use of either homologous or heterologous vaccine booster doses.[286][287] The authorization was expanded to include all adults in November 2021.[288]

Bivalent booster vaccination

In August 2022, the "Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)" (in short: "COVID-19 Vaccine, Bivalent") received an emergency use authorization from the US Food and Drug Administration (FDA) for use as a booster dose in individuals aged twelve years of age and older. One dose contains 15 mcg of "a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)" and 15 mcg "of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5)".[296]

The bivalent vaccine authorized in the United States is different from the one that was authorized for use in the United Kingdom[73] as the latter contains as second modRNA component 15 mcg of modRNA enocoding the S gylcoprotein of the earlier BA.1 variant.[73]

In September 2022, the European Union authorized both the BA.1 and the BA.4/BA.5 booster versions of the bivalent vaccine for people aged twelve years of age and older.[2][3][75]

While the Omicron BA.1 vaccine has been tested in a clinical study, the Omicron BA.4/BA.5 vaccine was only tested in pre-clinical studies. According to the published presentation,[297] the neutralization responses of Omicron BA.4/BA.5 monovalent, Omicron BA.1 mononvalent, Omicron BA.4/BA.5 bivalent and the original BNT162b2 vaccine have been explored in a study with BALB/c-mice.[298][299]

In October 2022, the FDA amended the authorization for the bivalent booster to cover people aged five years of age and older.[300]

In December 2022, the FDA amended the authorization for the bivalent booster to be used as the third dose in people aged six months through four years of age.[301]

XBB.1.5 monovalent vaccine

In September 2023, the FDA approved an updated monovalent (single) component Omicron variant XBB.1.5 version of the vaccine (Comirnaty 2023–2024 formula) as a single dose for individuals aged twelve years of age and older;[29] and authorized the Pfizer-BioNTech COVID-19 Vaccine 2023–2024 formula under emergency use for individuals aged 6 months through 11 years of age.[28][302] The approvals and emergency authorizations for the bivalent versions of the vaccine were revoked.[28] Health Canada approved the Pfizer-BioNTech Comirnaty Omicron XBB.1.5 subvariant, monovalent COVID‑19 vaccine in September 2023.[20] The UK Medicines and Healthcare products Regulatory Agency approved the used of the Comirnaty Omicron XBB.1.5 vaccine in September 2023.[303][304]

Society and culture

About 649 million doses of the Pfizer–BioNTech COVID-19 vaccine, including about 55 million doses in children and adolescents (below 18 years of age) were administered in the EU/EEA from authorization to 26 June 2022.[305]

Brand names

 
Comirnaty

BNT162b2 was the code name during development and testing,[46][56] tozinameran is the international nonproprietary name (INN),[39][306] and Comirnaty is the brand name.[41][2] According to BioNTech, the name Comirnaty "represents a combination of the terms COVID‑19, mRNA, community, and immunity".[307][308]

Famtozinameran is the INN for the BA.5 variant in the bivalent version of the vaccine.[309][310][311][312][6]

Raxtozinameran is the INN for the XBB 1.5 variant version of the vaccine.[39][313][314][315][6]

Economics

Pfizer reported revenue of US$154 million from the Pfizer–BioNTech COVID-19 vaccine in 2020,[179] and $36 billion in 2021.[316][317]

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.[45][318][319][320][321] By mid-December 2020, Pfizer had agreements to supply 300 million doses to the European Union,[322] 120 million doses to Japan,[323] 40 million doses (10 million before 2021) to the United Kingdom,[162] 20 million doses to Canada,[324] an unspecified number of doses to Singapore,[325] and 34.4 million doses to Mexico.[326] Fosun also has agreements to supply 10 million doses to Hong Kong and Macau.[327]

Pfizergate investigation

Accounts of how Pfizer's got its way into a large deal to provide 1.8 billion doses of its vaccine to the European Union were described by The New York Times as "a striking alignment of political survival and corporate hustle".[328] Shots worth €4 billion were reportedly wasted before the deal was re-negotiated. In early 2023, Belgian prosecutors began investigating European Commission President Ursula von der Leyen and Pfizer CEO Albert Bourla. The case was taken over in 2024 by the European Public Prosecutor's Office citing "interference in public functions, destruction of SMS, corruption and conflict of interest."[329]

Access

Pfizer has been accused of hindering vaccine equity. In 2021, Pfizer delivered only 39% of the contractually agreed doses to the COVAX programme, a number that equals 1.5% of all vaccines produced by Pfizer. The company sold 67% of their doses to high-income countries and sold none directly to low-income countries.[330]

Pfizer actively lobbied against the temporary lift of intellectual property rights which would allow the vaccine to be produced by others without having to pay a royalty fee.[331][332]

Misinformation

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.[333][334][335][336]

Notes

  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.[58]
  2. ^ No cases in the placebo group results in division by zero.
  1. ^ This is a type of study where researchers recruit two groups: people who test positive for the disease (cases) and those who test negative (controls) (Vandenbroucke 2019). They then survey these individuals for factors which may have affected whether or not they developed the disease (in this case, vaccination status) (Patel 2020). In the case of Lopez Bernal et al, they also assessed which variant each "case" contracted (e.g. alpha [B.1.1.7] or delta [B.1.617.2]) using both RT-PCR testing and whole genome sequencing. To evaluate efficacy, the researchers determined how much less likely a person was to contract each variant based on their vaccination status. In this case, a person who received two doses of the Pfizer vaccine was 93.7% less likely to contract the alpha variant and 88.0% less likely to contract the delta variant, when compared to an unvaccinated person.
    • Vandenbroucke JP, Pearce N (November 2019). "Test-Negative Designs: Differences and Commonalities with Other Case-Control Studies with "Other Patient" Controls" (PDF). Epidemiology. 30 (6): 838–844. doi:10.1097/EDE.0000000000001088. PMID 31430265. S2CID 201117050. (PDF) from the original on 21 September 2021. Retrieved 31 August 2021.
    • Patel MM, Jackson ML, Ferdinands J (November 2020). "Postlicensure Evaluation of COVID-19 Vaccines". JAMA. 324 (19): 1939–40. doi:10.1001/jama.2020.19328. PMID 33064144. S2CID 222819843.

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January 01, 1970
pfizer, biontech, covid, vaccine, pfizer, vaccine, biontech, vaccine, redirect, here, manufacturers, pfizer, biontech, sold, under, brand, name, comirnaty, mrna, based, covid, vaccine, developed, german, biotechnology, company, biontech, development, biontech,. Pfizer vaccine and BioNTech vaccine redirect here For the manufacturers see Pfizer and BioNTech The Pfizer BioNTech COVID 19 vaccine sold under the brand name Comirnaty 2 32 is an mRNA based COVID 19 vaccine developed by the German biotechnology company BioNTech For its development BioNTech collaborated with the American company Pfizer to carry out clinical trials logistics and manufacturing 44 45 It is authorized for use in humans to provide protection against COVID 19 caused by infection with the SARS CoV 2 virus 2 30 The vaccine is given by intramuscular injection 34 It is composed of nucleoside modified mRNA modRNA that encodes a mutated form of the full length spike protein of SARS CoV 2 which is encapsulated in lipid nanoparticles 46 Initial guidance recommended a two dose regimen given 21 days apart 34 47 48 49 this interval was subsequently extended to up to 42 days in the United States 34 50 and up to four months in Canada 51 52 Pfizer BioNTech COVID 19 vaccineA vial of the Pfizer BioNTech COVID 19 vaccine for the U S marketVaccine descriptionTargetSARS CoV 2Vaccine typemRNAClinical dataTrade namesComirnaty 1 2 3 Other namesBNT162b2 COVID 19 mRNA vaccine nucleoside modified COVID 19 Vaccine mRNA 4 AHFS Drugs comMonographMedlinePlusa621003License dataEU EMA by INN US DailyMed Pfizer BioNTech COVID 19 vaccinePregnancycategoryAU B1 5 Routes ofadministrationIntramuscularATC codeJ07BN01 WHO Legal statusLegal statusAU S4 Prescription only 6 5 7 8 9 10 11 12 13 14 15 16 BR Approved 17 18 CA only Schedule D 19 20 21 22 23 24 UK Conditional marketing authorization granted 25 26 27 1 US only with standing order Approved for those aged 12 28 29 30 Emergency Use Authorization for those aged 6 months 11 years 31 32 30 33 34 35 36 37 38 39 EU Marketing authorization granted 2 3 40 CH Rx only further explanation needed 41 ZA Section 21 42 43 Full list of Pfizer BioNTech vaccine authorizationsIdentifiersCAS Number2417899 77 3PubChem SID434370509DrugBankDB15696UNII5085ZFP6SJKEGGD11971ChEMBLChEMBL4650429 Clinical trials began in April 2020 47 by November 2020 the vaccine had entered phase III clinical trials with over 40 000 people participating 53 Interim analysis of study data showed a potential efficacy of 91 3 in preventing symptomatic infection within seven days of a second dose and no serious safety concerns 49 54 Most side effects are mild to moderate in severity and resolve within a few days 2 55 Common side effects include mild to moderate pain at the injection site fatigue and headaches 56 57 Reports of serious side effects such as allergic reactions remain very rare a with no long term complications documented 2 59 The vaccine is the first COVID 19 vaccine to be authorized by a stringent regulatory authority for emergency use 60 61 and the first to be approved for regular use 41 In December 2020 the United Kingdom was the first country to authorize its use on an emergency basis 59 It is authorized for use at some level in the majority of countries 62 63 64 65 On 23 August 2021 the Pfizer BioNTech vaccine became the first COVID 19 vaccine to be approved in the US by the Food and Drug Administration FDA 29 32 66 The logistics of distributing and storing the vaccine present significant challenges due to the requirement for its storage at extremely low temperatures 67 In August 2022 a bivalent version of the vaccine Pfizer BioNTech COVID 19 Vaccine Bivalent was authorized for use as a booster dose in individuals aged twelve and older in the US 68 69 70 71 The following month the BA 1 version of the bivalent vaccine Comirnaty Original Omicron BA 1 or tozinameran riltozinameran 72 was authorized as a booster for use in the UK 73 74 75 The same month the European Union authorized both the BA 1 and the BA 4 BA 5 tozinameran famtozinameran booster versions of the bivalent vaccine 2 3 40 Contents 1 Medical uses 1 1 Effectiveness 1 2 Specific populations 2 Adverse effects 2 1 Allergy 2 2 Myocarditis 3 Pharmacology 3 1 Sequence 4 Chemistry 5 Manufacturing 5 1 Logistics 6 History 6 1 Funding 6 2 Clinical trials 6 2 1 Specific populations 6 3 Authorizations 6 3 1 Expedited 6 3 2 Standard 6 4 Further development 6 4 1 Homologous prime boost vaccination 6 4 2 Heterologous prime boost vaccination 6 4 3 Bivalent booster vaccination 6 4 4 XBB 1 5 monovalent vaccine 7 Society and culture 7 1 Brand names 7 2 Economics 7 3 Pfizergate investigation 7 4 Access 7 5 Misinformation 8 Notes 9 References 10 Further reading 11 External linksMedical usesThe Pfizer BioNTech COVID 19 vaccine is used to provide protection against COVID 19 caused by infection with the SARS CoV 2 virus by eliciting an immune response to the S antigen 1 2 30 39 The vaccine is used to reduce morbidity and mortality from COVID 19 34 The vaccine is supplied in a multidose vial as a white to off white sterile preservative free frozen suspension for intramuscular injection 30 39 76 It must be thawed to room temperature and diluted with normal saline before administration 39 76 The initial course consists of two doses 34 39 The World Health Organization WHO recommends an interval of three to four weeks between doses Delaying the second dose by up to twelve weeks increases immunogenicity even in older adults against all variants of concern 77 Authors of the Pitch study think that the optimal interval against the Delta variant is around eight weeks with longer intervals leaving receptors vulnerable between doses 77 A third fourth or fifth dose can be added in some countries 68 78 79 80 81 82 Effectiveness This section needs more reliable medical references for verification or relies too heavily on primary sources Please review the contents of the section and add the appropriate references if you can Unsourced or poorly sourced material may be challenged and removed Find sources Pfizer BioNTech COVID 19 vaccine news newspapers books scholar JSTOR November 2021 nbsp A test negative note 1 case control study published in August 2021 found that two doses of the BNT162b2 Pfizer vaccine had 93 7 effectiveness against symptomatic disease caused by the alpha B 1 1 7 variant and 88 0 effectiveness against symptomatic disease caused by the delta B 1 617 2 variant 83 Notably effectiveness after one dose of the Pfizer vaccine was 48 7 against alpha and 30 7 against delta similar to effectiveness provided by one dose of the ChAdOx1 nCoV 19 vaccine 84 On 27 August the U S Centers for Disease Control and Prevention CDC published a study reporting that the effectiveness against infection decreased from 91 81 96 to 66 26 84 when the Delta variant became predominant in the US which may be due to unmeasured and residual confounding related to a decline in vaccine effectiveness over time 85 Unless indicated otherwise the following effectiveness ratings are indicative of clinical effectiveness two weeks after the second dose A vaccine is generally considered effective if the estimate is 50 with a gt 30 lower limit of the 95 confidence interval 86 Effectiveness is generally expected to slowly decrease over time 87 Initial effectiveness by variant Doses Severity of illness Alpha Beta Gamma Delta Omicron Others circulating previously A 1 Asymptomatic 38 29 45 89 17 10 23 90 Not reported 30 17 41 89 Not reported 60 53 66 Symptomatic 27 13 39 89 43 22 59 91 33 15 47 89 Not reported 66 57 73 Hospitalization 83 62 93 B 0 0 19 90 56 9 to 82 91 94 46 99 B Not reported 78 61 91 2 Asymptomatic 92 90 93 89 75 71 79 90 Not reported 79 75 82 89 Not reported 92 88 95 Symptomatic 92 88 94 89 88 61 96 91 83 78 87 89 88 66 96 C 94 87 98 Hospitalization 95 78 99 B 100 74 100 90 100 D 91 96 86 99 B 70 62 76 95 87 55 100 3 E Symptomatic Not reported Not reported Not reported 96 89 99 F 76 56 86 G Not reported Surveillance study from 20 December 2020 to 1 February 2021 in Israel 88 During this period according to Nextstrain the dominant variant in Israel was lineage B 1 1 50 and the Alpha variant was becoming dominant a b c d Preliminary data of effectiveness against hospitalization referenced by Public Health England 92 93 Effectiveness drops to 49 24 65 in weeks 10 14 after the second dose and then stabilizes at 34 37 thereafter 94 A confidence interval was not provided so it is not possible to know the accuracy of this measurement Booster dose Efficacy data from a study with more than 10 000 participants 96 Effectiveness drops to about 45 10 weeks after the booster dose 97 94 On 12 November Public Health England reported a possible but extremely small reduction in effectiveness against symptomatic disease from the Delta sublineage AY 4 2 at longer intervals after the second dose 98 Preliminary data suggest that the effectiveness against the Omicron variant starts to decline in about 10 weeks either after the initial two dose regimen or after the booster dose 94 97 For other variants the effectiveness of the initial doses starts to decline in about six months 99 A case control study in Qatar from 1 January to 5 September 2021 found that effectiveness against infection peaked at 78 95 CI 76 79 in the first month after the second dose followed by a slow decline that accelerated after the fourth month reaching 20 at months 5 to 7 A similar trajectory was observed against symptomatic disease and against specific variants Effectiveness against severe disease hospitalization and death was more robust peaking at 96 93 98 in the second month and remaining almost stable through the sixth month declining thereafter 100 On 21 October a phase 3 trial showed that a booster dose given approximately 11 months after the second dose restored the protective effect to the 96 95 CI 89 99 efficacy level against symptomatic disease from the Delta variant 101 96 On 8 December Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide a similar level of neutralizing antibodies against the Omicron variant as seen after two doses against other variants 102 On 14 December private health insurer Discovery Health in collaboration with the South African Medical Research Council reported that real world data from more than 211 000 cases of COVID 19 in South Africa of which 78 000 were of the Omicron variant indicate that effectiveness against the variant after two doses is about 70 against hospital admission and 33 against symptomatic disease Protection against hospital admission is maintained for all ages and groups with comorbidities 103 A study of the bivalent booster effectiveness against severe COVID 19 outcomes in Finland September 2022 January 2023 has shown that it reduced the risk of severe COVID 19 outcomes among the elderly By contrast among the chronically ill 18 64 year olds the risk was similar among those who received bivalent vaccine and those who did not Among the elderly a bivalent booster provided highest protection during the first two months after vaccination but thereafter signs of waning were observed The effectiveness among individuals aged 65 79 years and those aged 80 years or more was similar 104 Specific populations Based on the results of a preliminary study the U S Centers for Disease Control and Prevention CDC recommends that pregnant women get vaccinated with the COVID 19 vaccine 105 106 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 children aged between 12 and 15 years 107 108 On 19 May 2021 experts commissioned by the Norwegian Medicines Agency concluded that the Pfizer BioNTech vaccine is the likely cause of ten deaths of frail elderly patients in Norwegian nursing homes They said that people with very short life expectancies have little to gain from vaccination having a real risk of adverse reactions in the last days of life and of dying earlier 109 A 2021 report by the New South Wales Government NSW Health in Australia found that the Pfizer BioNTech vaccine is safe for those with 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 with cancer inflammatory bowel disease and various liver diseases be prioritised in the vaccination schedules over other patients that do not have said conditions 110 On 20 September 2021 Pfizer announced that a clinical trial conducted in more than 2 200 children aged 5 11 has generated a robust response and is safe 111 112 Adverse effectsSee also Vaccine adverse event In Phase III trials for the vaccine there were no safety concerns and few adverse events 49 54 Most side effects of the Pfizer BioNTech COVID 19 vaccine are mild to moderate in severity and are gone within a few days 55 2 They are similar to other adult vaccines and are normal signs that the body is building protection to the virus 55 During clinical trials the common side effects affecting more than one in 10 people are in order of frequency pain and swelling at the injection site tiredness headache muscle aches chills joint pain fever or diarrhea 113 Fever is more common after the second dose 113 The European Medicines Agency EMA regularly reviews the data on the vaccine s safety The safety report published on 8 September 2021 by the EMA was based on over 392 million doses administered in the European Union 2 According to the EMA 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 2 Rare side effects that may affect up to one in 1 000 people include temporary one sided facial drooping and allergic reactions such as hives or swelling of the face 2 Allergy Documented hypersensitivity to polyethylene glycol PEG a very rare allergy is listed as a contraindication to the COVID 19 Pfizer vaccine 114 Severe allergic reaction has been observed in approximately eleven cases per million doses of vaccine administered 115 116 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 115 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 117 118 119 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 120 Myocarditis In June 2021 the Israel s Ministry of Health announced a probable relationship between the second dose and myocarditis in a small group of 16 30 year old men 121 Between December 2020 and May 2021 there were 55 cases of myocarditis per 1 million people vaccinated 95 of which were classified as mild and most spent no more than four days in the hospital 121 Since April 2021 increasing number of cases of myocarditis and pericarditis have been reported in the United States in about 13 per 1 million young people mostly male and over the age of 16 after vaccination with the Pfizer BioNTech or the Moderna vaccine 122 123 Most affected individuals recover quickly with adequate treatment and rest 124 Since February 2022 the German Standing Committee on Vaccination recommends aspiration for COVID 19 vaccination as precautionary measure 125 PharmacologySee 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 126 triggering an immune response against infection by the virus protein 127 Sequence The modRNA sequence of the vaccine is 4 284 nucleotides long 128 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 46 129 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 130 and a poly A tail comprising 30 adenosine residues a 10 nucleotide linker sequence and 70 other adenosine residues bases 4175 4284 128 The sequence contains no uridine residues they are replaced by 1 methyl 3 pseudouridylyl 128 The 2P proline substitutions in the spike proteins were originally developed for a Middle East respiratory syndrome 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 129 ChemistryIn addition to the mRNA molecule the vaccine contains the following inactive ingredients excipients 26 120 113 ALC 0315 4 hydroxybutyl azanediyl bis hexane 6 1 diyl bis 2 hexyldecanoate ALC 0159 2 polyethylene glycol 2000 N N ditetradecylacetamide 1 2 distearoyl sn glycero 3 phosphocholine DSPC cholesterol dibasic sodium phosphate dihydrate monobasic potassium phosphate potassium chloride sodium chloride sucrose water for injection The first four of these are lipids The lipids and modRNA together form nanoparticles that act not only as carriers to get the modRNA into the human cells but also as adjuvants 131 ALC 0159 is a polyethylene glycol conjugate i e a PEGylated lipid 132 Manufacturing nbsp 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 the vaccine in China was purchased by Fosun alongside its investment in BioNTech 45 133 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 134 at a small Pfizer pilot plant in Chesterfield Missouri 135 136 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 137 The second stage is being conducted at a Pfizer plant in Andover Massachusetts 138 in the United States and at BioNTech s plants in Germany 134 The DNA is used as a template to build the desired mRNA strands 137 which takes about four days 134 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 137 nbsp A Pfizer employee putting dry ice in a box to protect the COVID 19 vaccines during transport at the Puurs factory nbsp Boxes containing the COVID 19 vaccines at the Pfizer factory in Puurs nbsp Inside view of Pfizer factory in Puurs External videos nbsp Loading dock operations at Pfizer s Portage Michigan facility December 13 2020 C SPAN nbsp President Joe Biden and Michigan Gov Gretchen Whitmer tour the Portage Michigan Pfizer facility with Pfizer CEO Albert Bourla February 19 2021 C SPAN The third stage is being conducted at Pfizer plants in Portage Michigan 139 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 137 Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids 140 As of November 2020 the major bottleneck in the manufacturing process is combining mRNA with lipid nanoparticles 137 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 134 Before May 2021 141 the Pfizer plant in Puurs was responsible for all vials for destinations outside the United States 134 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 134 In February 2021 BioNTech announced it would increase production by more than 50 to manufacture 2 billion doses in 2021 142 raised again at the end of March to 2 5 billion doses in 2021 143 In February 2021 Pfizer revealed that the entire sequence initially took about 110 days on average from start to finish and that the company is making progress on reducing the time to 60 days 144 More than half the days in the production process are dedicated to rigorous testing and quality assurance at each of the three stages 144 Pfizer also revealed that the process requires 280 components and relies upon 25 suppliers located in 19 countries 134 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 144 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 144 nbsp Syringes containing Pfizer COVID 19 vaccine dosesBioNTech 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 145 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 that produces the vaccine while Pfizer operates at least four production sites in the United States and Europe 145 The Marburg facility had previously specialized in cancer immunotherapy for Novartis 146 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 146 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 146 On 23 April 2021 the EMA authorized 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 147 148 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 141 LogisticsThe vaccine is delivered in vials that once diluted contain 2 25 mL of vaccine comprising 0 45 mL frozen and 1 8 mL diluent 149 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 149 150 The use of low dead space syringes to obtain the additional doses is preferable and partial doses within a vial should be discarded 149 151 The Italian Medicines Agency officially authorized the use of excess doses remaining within single vials 152 The Danish Health Authority allows mixing partial doses from two vials 153 As of 8 January 2021 each vial contains six doses 113 154 155 151 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 156 nbsp 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 can be stored at 2 to 8 C 36 to 46 F for thirty days before use 157 158 and at 25 C 77 F 26 30 or 30 C 86 F 159 8 for up to two hours before use During distribution the vaccine is stored in special containers that maintain temperatures between 80 and 60 C 112 and 76 F 160 Low income countries have limited cold chain capacity for ultracold transport and storage of a vaccine 161 The necessary storage temperatures for the vaccine 160 162 161 163 164 are 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 165 166 HistoryBefore 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 167 The SARS CoV 2 virus which causes COVID 19 was detected in December 2019 168 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 triggering an urgent international response to prepare for an outbreak and hasten development of preventive vaccines 169 170 The vaccine s development began when BioNTech founder Ugur Sahin 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 171 BioNTech started its program Project Lightspeed to develop a vaccine against the new COVID 19 virus based on its already established mRNA technology 53 which they had been developing since leading mRNA researcher Katalin Kariko joined the company in 2013 172 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 173 Meanwhile since 2018 Pfizer had been working with BioNTech on developing a mRNA vaccine for influenza but the chief executive officers of the two companies did not become personally acquainted until COVID 19 came along 174 After a few phone calls Pfizer CEO Albert Bourla and Sahin agreed that their companies would work together on the development of BioNTech s COVID 19 vaccine 174 The two agreed to begin work immediately with no formal written legal agreement in place to govern the new collaboration 174 BioNTech transferred its know how to Pfizer the next day 174 A letter of intent was signed three weeks later and the formal commercial agreement between Pfizer and BioNTech for the COVID 19 vaccine was signed in January 2021 174 Funding According to Pfizer research and development for the vaccine cost close to US 1 billion 175 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 176 133 In April 2020 BioNTech signed a partnership with Pfizer and received 185 million including an equity investment of approximately 113 million 177 178 179 In June 2020 BioNTech received 100 million US 119 million in financing from the European Commission and European Investment Bank 180 The Bank s deal with BioNTech started early in the pandemic when the Bank s staff reviewed its portfolio and came up with BioNTech as one of the companies capable of developing a COVID 19 vaccine The European Investment Bank had already signed a first transaction with BioNTech in 2019 181 In September 2020 the German government granted BioNTech 375 million US 445 million for its COVID 19 vaccine development program 182 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 183 Clinical trials See also COVID 19 vaccine clinical research Trial and authorization status 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 47 53 The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech 127 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 184 46 185 186 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 46 During the same month the European Medicines Agency EMA began a periodic review of BNT162b2 187 The study of BNT162b2 is a continuous phase trial in phase III as of November 2020 47 It is a randomized placebo controlled observer blind dose finding vaccine candidate selection and efficacy study in healthy individuals 47 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 49 133 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 47 The Phase III results indicating a 95 efficacy of the developed vaccine were published on 18 November 2020 53 For approval in the EU an overall vaccine efficacy of 95 was confirmed by the EMA 188 The EMA clarified that the second dose should be administered three weeks after the first dose 189 nbsp 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 190 At 14 days after dose 1 the cumulative incidence begins to diverge between the vaccinated group and the placebo group The highest concentration of neutralizing antibodies is reached 7 days after dose 2 in younger adults and 14 days after dose 2 in older adults 188 Vaccine efficacy against confirmed symptomatic COVID 19 188 Endpoint subgroup Efficacy 95 confidence interval All ages 95 0 90 0 97 9 Age 12 17 Not estimable b Age 18 64 95 1 89 6 98 1 Age 65 74 92 9 53 1 99 8 Age 75 100 0 13 1 to 100 0 All ages after dose 1 before dose 2 52 4 29 5 68 4 All ages 10 days after dose 1 before dose 2 86 7 68 6 95 4 All ages lt 7 days after dose 2 90 5 61 0 98 9 All ages 7 days after dose 2 94 8 89 8 97 6 All ages USA 94 9 88 6 98 2 All ages Argentina 97 2 83 3 99 9 All ages Brazil 87 7 8 1 99 7 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 49 191 162 High antibody activity persists for at least three months after the second dose with an estimated antibody half life of 55 days From these data one study suggested that antibodies might remain detectable for around 554 days 192 Specific populations Pfizer and BioNTech started a Phase II III randomized control trial in healthy pregnant women 18 years of age and older NCT04754594 193 The study will evaluate 30 mcg 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 194 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 195 In January 2021 Pfizer said it had finished enrolling 2 259 children aged between 12 and 15 years to study the vaccine s safety and efficacy 196 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 197 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 198 On 2 November 2021 The BMJ published a piece by journalist Paul D Thacker alleging there has been poor practice at Ventavia one of the companies involved in the phase III evaluation trials of the Pfizer vaccine 199 The report was enthusiastically embraced by anti vaccination activists David Gorski commented in Science Based Medicine that Thacker s article presented facts without necessary context to misleading effect playing up the seriousness of the noted problems 200 Authorizations Graphs are unavailable due to technical issues There is more info on Phabricator and on MediaWiki org Full authorization Emergency authorization Eligible COVAX recipient See also List of COVID 19 vaccine authorizations Pfizer BioNTech Although jointly developed with Pfizer 201 Comirnaty is based on BioNTech s proprietary mRNA technology 201 and BioNTech holds the Marketing Authorization in the United States the European Union the UK and Canada 201 expedited licenses such as the US emergency use authorization EUA are held jointly with Pfizer in many countries 201 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 60 It is the first COVID 19 vaccine to be approved for national use after undergoing large scale trials 202 and the first mRNA vaccine to be authorized for use in humans 60 203 The United Kingdom thus became the first Western country to approve a COVID 19 vaccine for national use 204 although the decision to fast track the vaccine was criticized by some experts 205 After the United Kingdom the following countries and regions expedited processes to approve the Pfizer BioNTech COVID 19 vaccine for use Argentina 206 Australia 207 Bahrain 208 Canada 209 210 Chile 211 Costa Rica 212 Ecuador 211 Hong Kong 213 Iraq 214 Israel 215 Jordan 216 Kuwait 217 Malaysia 218 Mexico 219 220 Oman 221 Panama 222 the Philippines 223 Qatar 224 Saudi Arabia 225 226 227 Singapore 228 229 230 South Korea 231 232 the United Arab Emirates 233 the United States 234 and Vietnam 235 The World Health Organization WHO authorized it for emergency use 236 237 238 239 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 Food and Drug Administration FDA 240 Pfizer applied for an EUA on 20 November 2020 241 and the FDA approved the application three weeks later on 11 December 2020 The US Centers for Disease Control and Prevention CDC Advisory Committee on Immunization Practices ACIP approved recommendations for vaccination of those aged sixteen years or older 242 243 Following the EUA issuance BioNTech and Pfizer continued the Phase III clinical trial to finalize safety and efficacy data leading to application for licensure approval of the vaccine in the United States 240 33 149 On 10 May 2021 the US FDA also authorized the vaccine for people aged 12 to 15 under an expanded EUA 244 33 149 245 150 The FDA recommendation was endorsed by the ACIP and adopted by the CDC on 12 May 2021 246 247 In October 2021 the EUA was expanded to include children aged 5 through 11 years of age 248 In June 2022 the EUA was expanded to include children aged six months through four years of age 31 On 16 February 2021 the South African Health Products Regulatory Authority SAHPRA in South Africa issued Section 21 Emergency Use Approval for the vaccine 249 250 On 5 May 2021 Health Canada authorized the vaccine for people aged 12 to 15 251 252 On 18 May 2021 Singapore s Health Sciences Authority authorized the vaccine for people aged 12 to 15 253 The European Medicines Agency EMA followed suit on 28 May 2021 254 On 4 June 2021 the UK Medicines and Healthcare products Regulatory Agency MHRA came to a similar decision and approved the use of the vaccine for people twelve years of age and older 26 107 108 Standard On 19 December 2020 the Swiss Agency for Therapeutic Products Swissmedic granted temporary authorization for 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 41 255 256 257 258 259 260 This is the first authorization under a standard procedure 41 255 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 2 261 3 The recommendation was accepted by the European Commission the same day 261 262 On 23 February 2021 the Brazilian Health Regulatory Agency approved the Pfizer BioNTech COVID 19 vaccine under its standard marketing authorization procedure 263 264 265 266 In June 2021 the approval was extended to those aged twelve or over 267 268 Pfizer s negotiation process with Brazil and other Latin American countries was described as bullying The contract prohibits the state of Brazil from publicly discussing the existence or the terms of their agreement with Pfizer BioNTech without the former s written consent Brazil was also restricted from donating or receiving donations of vaccines 269 270 In July 2021 the U S Food and Drug Administration FDA granted priority review designation for the biologics license application BLA for the Pfizer BioNTech COVID 19 vaccine with a goal date for the decision in January 2022 271 272 On 23 August 2021 the FDA approved the vaccine for use for those aged sixteen years and older 32 66 29 The Pfizer BioNTech Comirnaty COVID 19 vaccine was authorized in Canada in September 2021 for people aged twelve and older 20 21 19 273 In July 2022 the FDA approved the vaccine for use for those aged twelve years and older 274 29 In September 2022 the CHMP of the EMA recommended converting the conditional marketing authorizations of the vaccine into standard marketing authorizations 40 The recommendation covers all existing and upcoming adapted Comirnaty vaccines including the adapted Comirnaty Original Omicron BA 1 tozinameran riltozinameran and Comirnaty Original Omicron BA 4 5 tozinameran famtozinameran 2 40 Further development Homologous prime boost vaccination See also COVID 19 vaccine clinical research Homologous prime boost vaccination In July 2021 Israel s Prime Minister announced that the country was rolling out a third dose of the Pfizer BioNTech vaccine to people over the age of 60 based on data that suggested significant waning immunity from infection over time for those with two doses 275 The country expanded the availability to all Israelis over the age of 12 after five months since their second shot On 29 August 2021 Israel s coronavirus czar announced that Israelis who had not received a booster shot within six months of their second dose would lose access to the country s green pass vaccine passport 276 Studies performed in Israel found that a third dose reduced the incidence of serious illness 277 In August 2021 the United States Department of Health and Human Services HHS announced a plan to offer a booster dose eight months after the second dose citing evidence of reduced protection against mild and moderate disease and the possibility of reduced protection against severe disease hospitalization and death 278 The US Food and Drug Administration FDA and the Centers for Disease Control and Prevention CDC authorized the use of an additional mRNA vaccine dose for immunocompromised individuals at that time 78 79 Scientists and the WHO noted in August 2021 the lack of evidence on the need for a booster dose for healthy people and that the vaccine remains effective against severe disease months after administration 279 In a statement the WHO and Strategic Advisory Group of Experts SAGE said that while protection against infection may be diminished protection against severe disease will likely be retained due to cell mediated immunity 280 Research into optimal timing for boosters is ongoing and a booster too early may lead to less robust protection 281 In September 2021 the FDA and CDC authorizations were extended to provide a third shot for other specific groups 282 283 284 In October 2021 the European Medicines Agency EMA stated that a booster shot of the vaccine could be given to healthy people aged 18 years and older at least six months after their second dose 80 It also stated that people with severely weakened immune systems can receive an extra dose of either the Pfizer BioNTech vaccine or the Moderna vaccine starting at least 28 days after their second dose 80 The final approval to provide booster shots in the European Union will be decided by each national government 285 In October 2021 the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses 286 287 288 In October 2021 the Australian Therapeutic Goods Administration TGA provisionally approved a booster dose of Comirnaty for people 18 years of age and older 289 290 In January 2022 the FDA expanded the emergency use authorization to provide for the use of a vaccine booster dose to those aged 12 through 15 years of age and it shortened the waiting period after primary vaccination to five months from six months 291 292 293 294 In May 2022 the FDA expanded the emergency use authorization to provide for the use of a vaccine booster dose to those aged 5 through 11 years of age 295 In August 2022 the FDA revoked the emergency use authorization for the monovalent vaccine booster for people aged twelve years of age and older and replaced it with an emergency use authorization for the bivalent vaccine booster dose for the same age group 68 Heterologous prime boost vaccination For use as a heterologous booster dose see Oxford AstraZeneca COVID 19 vaccine Heterologous prime boost vaccination See also COVID 19 vaccine clinical research Heterologous prime boost vaccination In October 2021 the US Food and Drug Administration FDA and the Centers for Disease Control and Prevention CDC authorized the use of either homologous or heterologous vaccine booster doses 286 287 The authorization was expanded to include all adults in November 2021 288 Bivalent booster vaccination In August 2022 the Pfizer BioNTech COVID 19 Vaccine Bivalent Original and Omicron BA 4 BA 5 in short COVID 19 Vaccine Bivalent received an emergency use authorization from the US Food and Drug Administration FDA for use as a booster dose in individuals aged twelve years of age and older One dose contains 15 mcg of a nucleoside modified messenger RNA modRNA encoding the viral spike S glycoprotein of SARS CoV 2 Wuhan Hu 1 strain Original and 15 mcg of modRNA encoding the S glycoprotein of SARS CoV 2 Omicron variant lineages BA 4 and BA 5 Omicron BA 4 BA 5 296 The bivalent vaccine authorized in the United States is different from the one that was authorized for use in the United Kingdom 73 as the latter contains as second modRNA component 15 mcg of modRNA enocoding the S gylcoprotein of the earlier BA 1 variant 73 In September 2022 the European Union authorized both the BA 1 and the BA 4 BA 5 booster versions of the bivalent vaccine for people aged twelve years of age and older 2 3 75 While the Omicron BA 1 vaccine has been tested in a clinical study the Omicron BA 4 BA 5 vaccine was only tested in pre clinical studies According to the published presentation 297 the neutralization responses of Omicron BA 4 BA 5 monovalent Omicron BA 1 mononvalent Omicron BA 4 BA 5 bivalent and the original BNT162b2 vaccine have been explored in a study with BALB c mice 298 299 In October 2022 the FDA amended the authorization for the bivalent booster to cover people aged five years of age and older 300 In December 2022 the FDA amended the authorization for the bivalent booster to be used as the third dose in people aged six months through four years of age 301 XBB 1 5 monovalent vaccine In September 2023 the FDA approved an updated monovalent single component Omicron variant XBB 1 5 version of the vaccine Comirnaty 2023 2024 formula as a single dose for individuals aged twelve years of age and older 29 and authorized the Pfizer BioNTech COVID 19 Vaccine 2023 2024 formula under emergency use for individuals aged 6 months through 11 years of age 28 302 The approvals and emergency authorizations for the bivalent versions of the vaccine were revoked 28 Health Canada approved the Pfizer BioNTech Comirnaty Omicron XBB 1 5 subvariant monovalent COVID 19 vaccine in September 2023 20 The UK Medicines and Healthcare products Regulatory Agency approved the used of the Comirnaty Omicron XBB 1 5 vaccine in September 2023 303 304 Society and cultureAbout 649 million doses of the Pfizer BioNTech COVID 19 vaccine including about 55 million doses in children and adolescents below 18 years of age were administered in the EU EEA from authorization to 26 June 2022 305 Brand names nbsp Comirnaty BNT162b2 was the code name during development and testing 46 56 tozinameran is the international nonproprietary name INN 39 306 and Comirnaty is the brand name 41 2 According to BioNTech the name Comirnaty represents a combination of the terms COVID 19 mRNA community and immunity 307 308 Famtozinameran is the INN for the BA 5 variant in the bivalent version of the vaccine 309 310 311 312 6 Raxtozinameran is the INN for the XBB 1 5 variant version of the vaccine 39 313 314 315 6 Economics Pfizer reported revenue of US 154 million from the Pfizer BioNTech COVID 19 vaccine in 2020 179 and 36 billion in 2021 316 317 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 45 318 319 320 321 By mid December 2020 Pfizer had agreements to supply 300 million doses to the European Union 322 120 million doses to Japan 323 40 million doses 10 million before 2021 to the United Kingdom 162 20 million doses to Canada 324 an unspecified number of doses to Singapore 325 and 34 4 million doses to Mexico 326 Fosun also has agreements to supply 10 million doses to Hong Kong and Macau 327 Pfizergate investigation Accounts of how Pfizer s got its way into a large deal to provide 1 8 billion doses of its vaccine to the European Union were described by The New York Times as a striking alignment of political survival and corporate hustle 328 Shots worth 4 billion were reportedly wasted before the deal was re negotiated In early 2023 Belgian prosecutors began investigating European Commission President Ursula von der Leyen and Pfizer CEO Albert Bourla The case was taken over in 2024 by the European Public Prosecutor s Office citing interference in public functions destruction of SMS corruption and conflict of interest 329 Access Pfizer has been accused of hindering vaccine equity In 2021 Pfizer delivered only 39 of the contractually agreed doses to the COVAX programme a number that equals 1 5 of all vaccines produced by Pfizer The company sold 67 of their doses to high income countries and sold none directly to low income countries 330 Pfizer actively lobbied against the temporary lift of intellectual property rights which would allow the vaccine to be produced by others without having to pay a royalty fee 331 332 Misinformation 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 333 334 335 336 Notes 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 58 No cases in the placebo group results in division by zero This is a type of study where researchers recruit two groups people who test positive for the disease cases and those who test negative controls Vandenbroucke 2019 They then survey these individuals for factors which may have affected whether or not they developed the disease in this case vaccination status Patel 2020 In the case of Lopez Bernal et al they also assessed which variant each case contracted e g alpha B 1 1 7 or delta B 1 617 2 using both RT PCR testing and whole genome sequencing To evaluate efficacy the researchers determined how much less likely a person was to contract each variant based on their vaccination status In this case a person who received two doses of the Pfizer vaccine was 93 7 less likely to contract the alpha variant and 88 0 less likely to contract the delta variant when compared to an unvaccinated person Vandenbroucke JP Pearce N November 2019 Test Negative Designs Differences and Commonalities with Other Case Control Studies with Other Patient Controls PDF Epidemiology 30 6 838 844 doi 10 1097 EDE 0000000000001088 PMID 31430265 S2CID 201117050 Archived PDF from the original on 21 September 2021 Retrieved 31 August 2021 Patel MM Jackson ML Ferdinands J November 2020 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