In the meantime, further progress has been made, supporting the early availability of certain vaccine candidates. Additional insights have also been gained regarding the expected distribution set-ups for the frontrunner vaccines BioNTech/Pfizer, Moderna & University of Oxford/AstraZeneca.
What are the recent developments in the race for a COVID-19 vaccine and expected availability?
Recently, as the 10th company, Bharat Biotech announced, the start of a Ph III trial of their inactivated SARS-CoV-2 virus vaccine candidate.
|Developing company||Type of vaccine & name||Necessary doses||Storage and shipment temperature||Country|
|BioNTech / Pfizer||mRNA : |
|2||–78°C||Germany and USA|
|University of Oxford / AstraZeneca||Recombinant viral vector (Adenovirus)|
ChAdOx1 nCoV-19 or AZD1222
|2||2 – 8°C||UK|
|2||2 – 8°C||Russia|
|J&J Janssen||Ad26.COV2.S Adenovirus Vector vaccine||1||2 – 8°C||USA|
|CanSino||Recombinant Adenovirus Type 5 Vector vaccine||1||2 – 8°C||China|
|2||2 – 8°C||China|
"adsorbed COVID-19 vaccine"
|2||2 – 8°C||China|
|Novavax||Protein-based recombinant spike protein nanoparticle plus adjuvant||2||2 – 8°C||USA|
|Bharat Biotech||Inactivated: |
|2||2 – 8°C||India|
Of those vaccine candidates in late phase clinical development, three are already at various stages of registration.
BioNTech was the first to publish efficacy values for their BNT162b2 mRNA vaccine candidate, derived from the Ph III (interim analysis and/or final) data. The observed efficacy of 95% is well above expectations. On the 2nd December the Medicines and Healthcare products Regulatory Authority (MHRA) in the UK were the first regulator to approve a COVID-19 vaccine. The rollout of the vaccine and immunization in the UK has already started this week.
BioNTech and their partner Pfizer also submitted their data to the FDA (Food & Drug Administration) to gain emergency use authorization (EUA) in the US, which may be granted as early as mid-December. This will facilitate vaccination of vulnerable populations in the US starting in December. BioNTech/Pfizer have further submitted application for Conditional Marketing Authorization for their COVID-19 vaccine to the EMA (European Medicines Agency) last week. The two companies plan to have 50 million doses of the BNT 162b2 vaccine available in 2020 and plan to produce 1.3 billion doses in 2021.
Next in line was Moderna with their mRNA-1273 vaccine candidate which reported an efficacy value of 94 %. Moderna filed for emergency use authorization with the US FDA at the end of November. Advisors to the US FDA are expected to evaluate the data at a public meeting on December 17, one week after a similar review is planned to be held for the Pfizer vaccine candidate. Moderna communicated, that they plan to provide Moderna`s entire US inventory to the federal government 24 to 72 hours after the vaccine is cleared. Last week the EMA also communicated the receipt of the application for Conditional Marketing Authorization of the Moderna COVID-19 vaccine. The company expects to have 50 million doses available in December and to produce up to 1 billion doses in 2021.
University of Oxford/AstraZeneca
Data from an interim analysis of AstraZeneca’s Adenovirus vector vaccine candidate was less impressive than that of BioNTech/Pfizer and Moderna, with an average efficacy of only 70%. The standard dosing regimen yielded an efficacy of 62%, while another dosing regimen was able to achieve 90%. These numbers are not conclusive, but are expected to consolidate once the full data is available. AstraZeneca expects to produce 400 million doses by the end of 2020 and 3 billion doses in 2021. AstraZeneca, too, is reported to be preparing a request for EUA.
The vaccine Sputnik V that is being developed by the Gamaleya Institute, had already received registration in Russia months ago, based only on the respective Ph II data. A current Phase III study is however underway. Data from this clinical trial suggested an efficacy of ~90%. Mainly countries in the Middle East and South America, such as Argentina (25 million doses) and the state of Bahia in Brazil (50 million doses) have shown interest in this vaccine candidate.
How does the temperature requirements of the frontrunner vaccine candidates affect the distribution set-up?
BioNTech Pfizer | Transport: -78°C, Dry Ice
The ultra-low temperature required to maintain the stability of the mRNA COVID-19 vaccine developed by BioNTech in cooperation with Pfizer, has obliged the companies to come up with a specialized distribution set-up, bypassing pharmaceutical wholesalers, that in this form and volume has never been executed before. The BNT162b2 vaccine will initially be manufactured at Pfizer's Kalamazoo (US) and Puurs (Belgium) site, from where they plan to move 7.6 million doses to airports every day. The vaccines are transported in insulated dry ice boxes with up to 5,000 doses per box. The boxes are expected to maintain the temperature at -78°C for up to 10 days. The temperature of the life-saving vaccines is monitored during delivery to the immunization centers by air and road transport using GPS trackers. Once thawed, the vaccine can be held in standard medical fridges at +2 to +8°C only for up to 5 days.
Whilst BioNTech/Pfizer have a clear strategy on how to deliver the vaccines to those countries that have committed to purchase the vaccine developed on an entirely new technology platform, some countries seem to lag behind on the readiness to supply the vaccine to their people at the end of this year or early next year. Where last minute purchases of ultra-low temperature freezers are no longer possible due to unavailability, training programs on the re-icing of temperature-controlled boxes can help to prolong the performance of the packaging and therefore the time the vaccines can be stored in such an environment. At every step of the supply chain, the necessary equipment to handle the hazardous goods, dry ice, and appropriately trained personnel are required.
Alternatively, storing of dry ice boxes in a deep-frozen environment will help to increase their performance. For example, the lifetime of dry ice boxes may be prolonged by a factor of 2 if stored in a reefer container at -30°C. Such reefer containers can hold up to 1 million vaccine doses.
Two questions that remain uncertain with regards to the volume distribution of the BioNTech/Pfizer vaccine at -78°C, are the availability of dry ice and how the limitation of dry ice quantities on aircrafts will affect distribution.
In the US, the Compressed Gas Association expressed confidence in being able to cover the spike in demand with the existing and increased production capacity. In addition, UPS has communicated that it has enhanced its ability to produce dry ice in the US and Canada. Dry ice producers in the UK have also communicated that they have no concerns about the additional dry ice demand and that the UK capacity could be increased by 50%. Less developed countries are likely to lack the resources to follow suit.
The existing regulations concerning the amount of dry ice per aircraft (between 500 to 1,000 kilos) present a potential bottleneck for the BNT162b2 distribution. With a maximum dose capacity of 5,000 per box, only approximately 250,000 doses of the BioNTech/ Pfizer vaccine could be transported per flight.
Moderna | Transport: -20°C
Like the BioNTech/Pfizer vaccine, the Moderna vaccine mRNA-1273 is developed on the mRNA technology platform, which has not yet been applied to any vaccines currently on the market. Contrary to BioNTech/Pfizer, the Moderna vaccine candidate can be shipped and stored in an environment found more readily available in the common pharmaceutical supply chain. The vaccine remains stable for up to 6 months at -20°C, including 30 days at standard refrigerator temperatures of +2 to 8°C once thawed. The vaccine is also stable at room temperature for 12 hours. Whilst Moderna has not communicated detailed distribution plans as BioNTech/Pfizer have, it can be expected that the distribution of the final product will take place at -20°C from the manufacturing sites to the pharmaceutical wholesalers. From there, the vaccines will be distributed to immunization centers, hospitals and doctors, where the vaccine can now be stored within the existing infrastructure at +2 to +8°C for 30 days.
University of Oxford/AstraZeneca | Transport: +2 to +8°C
AstraZeneca's AZD1222 is developed on the known technology platform of an adenovirus viral vector. The vaccine candidate can be stored and transported at standard refrigerated conditions of +2 to 8°C within the existing healthcare infrastructure for a minimum of six months.
AZD1222's temperature requirements provide a more viable option for the distribution to, and the cold chain infrastructure of, low- and middle-income countries. With their commitment to deliver one billion doses of their vaccine to low- and middle-income countries, AstraZeneca is promising to supply more doses outside of the US and Europe than any other of their close competitors.
How is the vaccine price going to affect the demand for the three COVID-19 vaccine candidate frontrunners?
Not only the distribution set-up but also the price of the COVID-19 vaccine candidates may affect demand. It must be noted that AstraZeneca’s adenovirus vector vaccine is significantly cheaper than the mRNA type vaccines.
Pfizer: USD 20 per dose
Moderna: USD 32 to 37 per dose for small volume agreements (lower price for larger volume agreements in discussion)
AstraZeneca: USD 3 to 4 per dose
This again suggests that AstraZeneca's vaccine is a more feasible candidate for less affluent countries.
How does the COVID-19 vaccine manufacturing and distribution affect the supply chain of other medicinal products?
All three frontrunner vaccine developers have started production of their vaccine candidate at risk, taking up significant production capacity at CMO manufacturers. Lead times for vials have not only been reported to have already increased greatly in Europe, but Chinese COVID-19 vaccine developer Sinopharm has also stated, that the shortages of packaging materials such as glass bottles and rubber plugs are limiting the speed at which vaccines can be made available. How the COVID-19 vaccine distribution is going to affect the pharmaceutical cold chain of other medicinal products, due to a potential lack of air freight, packaging materials and temperature-controlled warehouses remains unclear.
What is needed next?
As the availability of a COVID-19 vaccine candidate is within reach and manufacturers are getting ready for volume distribution, it is crucial that reliable infrastructures are implemented at country and state levels, that enable the safe handling and storage of the different vaccine candidates at administration sites, whether it be immunization centers, hospitals or doctors.
Toolkits such as provided by the U.S. Department of Health and Human Services provides important guidance on the correct storage and handling of the COVID-19 vaccines.
Vaccine Storage and Handling Toolkit (cdc.gov)