All the Details about Covid-19 Vaccine Pfizer–BioNTech, Production, Emergency Use Approval & Efficiency

The Pfizer–BioNTech COVID-19 vaccine, sold under the brand name Comirnaty, is an mRNA-based COVID-19 vaccine. It is authorized for use in people aged 12 years and older in some jurisdictions and for people 16 years and older in other jurisdictions, to provide protection against infection by the SARS-CoV-2 virus, which causes COVID-19. BioNTech, a German company, developed the vaccine and collaborated with Pfizer, an American company, for support with clinical trials, logistics, and manufacturing. In China, BioNTech is partnered with China-based Fosun Pharma for development, marketing, and distribution rights and the vaccine is colloquially described as the Fosun–BioNTech COVID-19 vaccine. The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Vaccination requires two doses given three weeks apart.

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

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

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

* Vaccine Composition:

In addition to the mRNA molecule, the vaccine contains the following inactive ingredients (excipients):

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 as adjuvants. ALC-0159 is a polyethylene glycol conjugate, i.e., a PEGylated lipid.

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

* Efficacy:

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. The Initial Pivotal Phase II–III Trial with the lead vaccine candidate "BNT162b2" began in July. The Phase III results indicating a 95% efficacy of the developed vaccine were published on 18 November 2020.

Preliminary results from Phase I–II clinical trials on BNT162b2, published in October 2020, indicated potential for its efficacy and safety. During the same month, the European Medicines Agency (EMA) began a periodic review of BNT162b2.

The study of BNT162b2 is a continuous-phase trial in Phase III as of November 2020.[32] It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals". The early-stage research determined the safety and dose level for two vaccine candidates, with the trial expanding 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.

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. For approval in the EU, an overall vaccine efficacy of 95% was confirmed by the EMA. The EMA clarified that the second dose should be administered three weeks after the first dose.





* Manufacturing:

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

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, at a small Pfizer pilot plant in Chesterfield, Missouri (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.

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

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

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

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

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. 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.

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. Once fully operational, the facility would produce up to 750 million doses per year, or more than 60 million doses per month. The site will be the third BioNTech facility in Europe which produces the vaccine, while Pfizer operates at least four production sites in the United States and Europe.

 

The Marburg facility had previously specialized in cancer immunotherapy for Novartis. 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. 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). - Published by The Beyond News (Breaking News).

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