The Pfizer–BioNTech COVID-19 vaccine, sold under the brand name Comirnaty,[2][32] is an
mRNA-basedCOVID-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-2virus.[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]
Clinical trials began in April 2020;[47] by November 2020, the vaccine had entered
phaseIII 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 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]
^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.
^
abcdPreliminary 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.
^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]
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]
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 392million 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 9December 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 1million 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 1million 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]
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]
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 10million doses. The bags are placed on trucks which take them to the next plant.[137]
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 2billion doses in 2021,[142] raised again at the end of March to 2.5billion 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]
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 750million doses per year, or more than 60million 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 8January 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 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$1billion.[175]
BioNTech received a US$135million investment from Fosun in March 2020, in exchange for 1.58million 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 $185million, including an equity investment of approximately $113million.[177][178][179]
In June 2020, BioNTech received €100million (US$119million) 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 €375million (US$445million) 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]
PhaseI–II Trials were started in Germany on 23 April 2020, and in the U.S. on 4May 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
phaseI trials on BNT162b1 in Germany and the United States, while Fosun performed a PhaseI trial in China. In these PhaseI studies, BNT162b2 was shown to have a better safety profile than the other three BioNTech candidates.[184][46][185][186]
The Pivotal PhaseII–III Trial with the lead vaccine candidate "BNT162b2" began in July. Preliminary results from
PhaseI–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
phaseIII 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 PhaseIII 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]
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]
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 PhaseII–III randomized control trial in healthy pregnant women 18 years of age and older (NCT04754594).[193] The study will evaluate 30mcg of BNT162b2 or placebo administered via intramuscular injection in two doses, 21 days apart. The PhaseII 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 PhaseIII 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 PhaseIII 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.
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 2December 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]
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 PhaseIII 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 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 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]
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]
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 15mcg of "a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)" and 15mcg "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 15mcg 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 649million doses of the Pfizer–BioNTech COVID-19 vaccine, including about 55million 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
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$154million 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$1.95billion with Pfizer to manufacture 100million 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 300million doses to the European Union,[322] 120million doses to Japan,[323] 40million doses (10million before 2021) to the United Kingdom,[162] 20million doses to Canada,[324] an unspecified number of doses to Singapore,[325] and 34.4million doses to Mexico.[326] Fosun also has agreements to supply 10million 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]
^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.
^
abcde"Comirnaty". Union Register of medicinal products. European Commission.
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^
ab"AusPAR: Tozinameran". Therapeutic Goods Administration (TGA). 8 February 2022.
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^Australian Government Department of Health (24 January 2021).
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^Rosales-Mendoza S, Wong-Arse A, de Lourdes Betancourt-Mendiola M (2021). "8. RNA based vaccines against SARS COV-2". In Rosales-Mendoza S, Comas-García M, González-Ortega O (eds.).
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^Krause P, Fleming TR, Longini I, Henao-Restrepo AM, Peto R, Dean NE, et al. (12 September 2020).
"COVID-19 vaccine trials should seek worthwhile efficacy". The Lancet. 396 (10253): 741–743.
doi:
10.1016/S0140-6736(20)31821-3.
ISSN0140-6736.
PMC7832749.
PMID32861315. WHO recommends that successful vaccines should show an estimated risk reduction of at least one-half, with sufficient precision to conclude that the true vaccine efficacy is greater than 30%. This means that the 95% CI for the trial result should exclude efficacy less than 30%. Guidance from the US Food and Drug Administration includes this lower limit of 30% as a criterion for vaccine licensure.
^"STIKO empfiehlt Aspiration bei COVID-19-Impfung als Vorsichtsmaßnahme" [STIKO recommends aspiration for COVID-19 vaccination as precautionary measure]. Deutsches Ärzteblatt (in German). 18 February 2022. Retrieved 25 September 2022. Im Tiermodell seien nach direkter intravenöser Gabe eines mRNA-Impfstoffs Perimyokarditiden aufgetreten. [In an animal model, perimyocarditis had occurred after direct intravenous administration of an mRNA vaccine.]
^Gosk S (1 April 2021).
"Inside Lab Where Every Pfizer Dose Originates". NBC Nightly News With Lester Holt. NBC News.
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YouTube. Gosk's segment on Pfizer begins at 7:10 of the video file.
^
ab"Deep-freeze hurdle makes Pfizer's vaccine one for the rich". Bloomberg. 10 November 2020.
Archived from the original on 22 November 2020. Retrieved 12 November 2020. Vaccine goes bad five days after thawing, requires two shots; Many nations face costly ramp up of cold-chain infrastructure
^
abcCommittee for Medicinal Products for Human Use (19 February 2021).
Assessment report: Comirnaty(PDF) (European public assessment report). Corr.1.
European Medicines Agency (EMA). COVID-19 Case Definitions; tables 2, 7, 8 and 10; All Confirmed Cases of COVID-19 After Dose 1; Favourable effects. EMA/707383/2020.
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^"Informe à população brasileira". Agência Nacional de Vigilância Sanitária - Anvisa (in Portuguese). 23 February 2021.
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^"COVID-19 vaccines safety update"(PDF).
European Medicines Agency (EMA). 3 August 2022. Retrieved 3 August 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^"COVID-19 Vaccine Myths And Facts"(PDF). Los Angeles County Department of Public Health. 15 December 2021.
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World Health Organization (WHO).
hdl:10665/338671. WHO/2019-nCoV/vaccines/SAGE_recommendation/BNT162b2/background/2021.1.
External links
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