Delivering COVID-19 vaccine part 2

Pushing boundaries to deliver COVID-19 vaccine across the Globe

Overview

AstraZeneca will deliver up to 3 billion doses of COVID-19 vaccine across the globe by the end of 2021 - which will be just 18 months after the company first partnered with the University of Oxford to develop and manufacture the vaccine.

Following a multi-stage manufacturing and quality testing process, batches will be delivered to distribution hubs across the globe. From there, governments and multilateral organisations with whom we have formed agreements will ensure fair allocation and distribution of the vaccine within their countries and regions.

As part of our commitment to providing broad and equitable access to COVID-19 vaccine, AstraZeneca will also supply the COVAX Facility, led by GAVI, the Coalition for Epidemic Preparedness Innovations (CEPI) and the World Health Organisation (WHO), which will distribute vaccine to low- and middle-income countries.

The successful start of vaccinations in the initial countries where it has been authorised for emergency supply is just the beginning for AstraZeneca.

Having established manufacturing capacity in 15 countries and 25 different manufacturing sites to supply vaccine to every region of the world as quickly as possible, we are responsible for ensuring that these facilities are working around the clock and with the highest standards of quality to meet the unprecedented demand and incredible global need.

Every batch of vaccine undergoes rigorous quality testing during each stage of the manufacturing process to ensure it meets the high standards of safety, purity and effectiveness specified in the manufacturing protocols and to ensure comparability across sites within our manufacturing network. Nothing is left to chance.

However, with thousands of COVID-19 related deaths every day, AstraZeneca has pursued every opportunity for refining and accelerating its processes to meet the urgency of the pandemic while still meeting our rigorous safety and quality standards.

In addition to rapidly building a team of hundreds of highly skilled workers from across nearly every part of our company and bringing in leading experts from our broader industry, we are doing everything in our power to accelerate and optimise the supply, production, testing and delivery processes.

Multiple manufacturing and testing processes are now carried out in parallel instead of consecutively – saving months of time compared to a traditional vaccine manufacturing process. This means that teams are using every available moment to analyse data in real-time, validate results, complete essential vaccine release paperwork, and get trucks on the road around the world to take consignments to government distribution hubs once all quality requirements are satisfied.

We continue to strive for even greater efficiency in vaccine production for combating the pandemic, and we are already looking beyond 2021 to identify global needs for COVID-19 vaccine after the pandemic. Our work here is not done.


Download the full factsheet


01

Introduction

AstraZeneca takes responsibility for the safety, effectiveness and quality of all the COVID-19 vaccine made in our global supply network of manufacturing facilities across Europe, North, Central and South America, Asia and Australia. This means that every batch made in our supply network must meet the same exacting production and quality standards.

At every stage of the production process there is a continuous demand to test, record, analyse, report, confirm and verify.

In a traditional drug supply chain, finished product may be stored for weeks or months until it is needed to meet public health requirements. However, in the current pandemic, it’s essential that every dose is available for administration as quickly as possible. This means that a  batch of COVID-19 vaccine can be shipped to national/regional distribution hubs within hours of the final release certificate being received from a government regulator.

AstraZeneca’s many years of experience manufacturing our live virus influenza vaccine meant that our COVID-19 vaccine operation was built on solid foundations and strong expertise. However, supplying a vaccine to combat an infection that threatens the entire world of nearly 8 billion people, has put unprecedented demand on all raw materials, limited manufacturing capacity and posed incredible operating constraints.

COVID-19-related travel restrictions on people and supplies, and workforce illness and need for self-isolation, have presented additional unique challenges.

Only through comprehensive planning, creative thinking, rapid problem solving, continuous collaboration with all our partners, and 24/7 commitment, have we been able to contribute to the global effort to overcome the COVID-19 pandemic.



When you set up production for a vaccine or medicine, the most important thing is to ensure you have rock solid control over all the production processes, with rigorous procedures in place to ensure the product is made to the correct standards of safety, efficacy and quality. Subsequent testing of your product should be confirmatory, it’s how you set up your processes at the beginning that’s key.

Dave Clark VP Technical Operations

02

Addressing the challenge of global vaccine demand

To help meet global demand for COVID-19 vaccine, AstraZeneca rapidly conducted due diligence with more than 60 potential partners to ultimately build a global supply network of more than 25 proven manufacturing organisations in 15 countries with the capability and capacity to supply the vaccine.  With each partner, the technology transfer process began immediately to ensure that not a minute was wasted in our quest to rapidly establish commercial manufacturing ahead of regulatory approval/authorisation. During this process, our technical experts worked around the clock with our supply partners to transfer our validated protocols and standard methods for vaccine production. As our teams were unable to travel due to the pandemic, we used virtual technology to provide real-time technical support and coaching to production teams on each site.

Every single step of each stage of the manufacturing process –  from growing and harvesting the vector vaccine to filling vials with the finished product, packing and labelling them –  is outlined in these protocols in great detail and has been agreed with regulatory authorities.

Many times a day, the same steps are repeated in every factory around the world where the vaccine is produced. Standard checks are made and data are reported back to AstraZeneca to confirm that production runs within agreed specifications. During this daily process, we work closely with our supply partners to capitalise on and share learnings in real-time – both best practices and challenges – in order to continually optimise the process and share these developments across the global supply network.

In addition to the precious vector vaccine DNA and producer cells, the manufacturing process requires a large number of raw materials (compounds that aid in the vaccine manufacturing process and/or that make up the final formulation), components (such as vials and stoppers), and consumables (such as filters and tubing). Highly coordinated, continuous supply of all these essential items for vaccine production is in place at each manufacturing facility.

Each raw material must be tested on arrival at the facility to ensure that it meets quality specifications and some components must be transported and stored at carefully controlled temperatures. For example, after the drug substance has been produced, it is frozen until manufacturers are ready to process it into finished vaccine and fill into vials. This helps to preserve the shelf-life of the product. Even when the vaccine has been formulated and put into vials, it must remain at the required 2-8°C. During this time, loading and unloading, transport and storage must all be carried out using strict temperature controls and electronic monitors are in place to ensure that the product remains within specification at all times.

Effective communication is key to ensuring the smooth flow of supplies, vaccine substance and finished vaccine between sites, and a team of AstraZeneca planners and logistics experts coordinate these movements and liaises with suppliers with growing frequency as sites prepare for the all-important release day.



In parallel to ensuring our production processes could be implemented across all our manufacturing sites, a key priority was to secure the raw materials and components needed to manufacture and supply the vaccine. This included sourcing the hundreds of millions of vials and stoppers we need. We knew there would be very high demand during the pandemic, so we sourced our supply of vials at a very early stage – well before we had significant quantities of vaccine to put in them.

Herminio Bosques Senior Director, Global Direct Materials and BioProcessing

03

Testing every batch of vaccine

Wherever our COVID-19 vaccine may be administered around the world, we need to know that it meets the same high standards of safety, efficacy and quality. Prior to signing supply agreements with our partners, they underwent a rigorous due diligence process that included a quality audit. In addition, each site must be licensed by the relevant regulatory authority and adhere to Good Manufacturing Practice (GMP). GMP ensures that products are consistently produced and controlled according to quality standards.

The last step before regular manufacturing can begin is the validation of the process to ensure that the essential conditions, controls, testing, and expected outcome are achieved. Once the process has been validated and manufacturing is underway, robust quality assurance processes are in place to reduce the possibility of unexpected changes to the vaccine during production. Where possible during the pandemic, we visit manufacturers to audit processes but, if this is not possible, monitoring includes virtual tours when our manufacturing partners take us around their facility so we can watch production processes in action.

Additionally, regular quality control testing is carried out to ensure the production process is well controlled and results are consistently within required levels. Each of these tests have been validated and has a specific step-by-step process that must be carried out.

Bulk vaccine substance is tested for safety and purity, and finished product is tested for efficacy, quality and consistency. Some batches are also tested for stability to check how long they can be stored and that they will not be affected by the changes in air temperature or pressure or the vibration they may experience on their journey to patients in remote places.

Nearly all of the safety testing of batches of vaccine made at our manufacturing plants is centralised. Samples from across the world are brought to these central laboratories to ensure the same high standards of specialist testing.

Each batch of the vaccine undergoes more than 40 different quality control tests during its journey from lab to jab. As the vaccine is based on biological materials, some of these tests take at least a month to complete, and cannot be rushed. However, where possible, we are performing this testing in parallel with the next phase of production to ensure that the batches move forward as rapidly as possible.



AstraZeneca’s global presence means that we can take advantage of the multiple time zones across which we work – passing the baton on aspects of our work so that progress continues while we sleep and we can achieve the speed needed to fight the pandemic without compromising safety, efficacy or quality.

Veera Padmanabhan Senior Director, BioOperations Analytical Network Lead

04

Vaccine batch release to national governments

Releasing the first batch of COVID-19 vaccine for transport to the UK government distribution hub, under emergency supply regulations, was an emotional day for the hundreds of people at AstraZeneca who had worked long days and nights to reach this momentous milestone.


There was an amazing sense of achievement to have built up all the documentation about the manufacture and checking of the first batch of vaccine all along the way, and to really know it inside out! To be told we could release the vaccine into clinics and be part of something which is going to help all of society get out of this pandemic and get back to living normally was an extraordinary feeling.

Rachel Gadsbey Quality Director, Supply and Quality Systems


It required that all stages of manufacture had been carried out in accordance with the product licence and the rules of Good Manufacturing Practice, and the specific batch of vaccine met the quality and safety specifications as confirmed by testing conducted by both AstraZeneca and in government testing laboratories.


05

The work that never stops

AstraZeneca is continually identifying and implementing new ways of working that will accelerate production of COVID-19 vaccine and reduce the time to reach communities.

Already, AstraZeneca scientists have discovered how to significantly reduce the amount of virus needed at the start of the process to infect producer cells from which the vaccine is harvested, making the process more efficient. Additionally, we have increased the concentration of the vaccine drug substance, which significantly reduced the amount of freezer storage required at the sites, as well as reducing the transportation and raw material requirements.

Our advances in enhancing vaccine production processes have important potential implications for developing treatments for other diseases. The urgency with which we are working on the COVID-19 vaccine has made us more agile in our production and testing processes, and the multiple successful collaborations and partnerships we have formed will strengthen our ability to respond rapidly to future health needs.

 


Related story

For more information also see delivering COVID-19 vaccine part 1:

Innovating Production and Manufacture to meet the Challenge of COVID-19



Veeva ID: Z4-30674
Date of Preparation: February 2021