EMA within the premises of the manufacturing facility. The virus bulk is then for-

mulated, filled in product containers, and then packaged in product containers. A

second formal release by the regulatory agency agents is conducted prior to shipping.

Additional regulatory assessments are conducted by regulatory agencies following

shipping and distribution through extensive testing and documentation of release

criteria [10].

The formulation of vaccines is an important step in the manufacturing pro-

cess. This would combine in the bulk vaccine, the antigen product with even-

tually adjuvants in the case of subunit vaccines and excipients that would

contribute to vaccine thermostability enabling delivery to remote areas. This step

will also involve a final fill, a sterile filtration, and eventually a freeze-drying in

the case of lyophilized vaccines prior to release and storage according to a pre-

determined cold chain. Adjuvants, as immune potentiators, play a role in the

delivery of the antigen as particulates or molecular structures acting as depot/

carriers of the antigen to immunostimulants, inducing a broader immune re-

sponse and providing a better protection while maintaining safety of the vaccine

product.

In the case of freeze-dried vaccine formulations, reconstitution of the vaccine

prior to injection is required. The principles of freeze-drying to remove the solvent,

usually water, from dissolved or dispersed vaccine will be described and ex-

emplified in case studies.

1.8

PANDEMIC PREPAREDNESS AND OUTLOOK

The current COVID-19 pandemic has put the focus on the development process of

vaccines and their safety and efficacy. However, this is not the first pandemic that

has occurred. By the end of World War I, in 1918, the Spanish Flu (which was an

H1N1 influenza-type virus) caused between 30 and 100 million deaths. SARS

(Severe Acute Respiratory Syndrome), with a mortality of 10%, appeared in China

in 2002. The H1N1 pandemic (2009), called the swine flu, showed that viruses can

transmit via animals. All these viruses are RNA viruses, meaning that evolution is

possible. MERS, Middle East Respiratory Syndrome, with a mortality of 30%,

appeared in Saudi Arabia in 2012. MERS has been thereafter associated with close

contact of humans with dromedary camels as the vehicle of disease transmission

and has spread to other countries [22].

The field of vaccines, particularly in the context of pandemic preparedness, re-

quires the development of new tools and methods to enable accelerated process and

product development and manufacturing. Eventually, all the vaccines that are under

development build on prior knowledge on vaccine design and manufacturing

technologies with emergence of paradigm shifts such as the messenger RNA

technology that led to the rapid development of COVID-19 mRNA vaccines within

unprecedented timelines. Importantly, the scale-up potential and the robustness of

the manufacturing technology for global delivery remain key drivers in the field of

vaccine development, requiring alliances of experts in vaccinology, virology, cell

biology, engineering, and medicine.

Viral vaccines

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