B.Pharm.

Industrial Training
Daily Report

Date: 07/06/2021 Time: 10:00- 4:00

Name of Session/Topic: Vaccine types and production

Name of Expert, Affiliation: Mr. Nilanshu Manocha, Senior Research Fellow, Amity Institute of
Virology & Immunology, Amity University.

Time Learning Where can you Question answer/Quiz

apply this
knowledge?
10:00 Classification of vaccines This knowledge is
-11:30 very useful and to
Live attenuated vaccines be applied during R
The virus or bacteria is functional/alive but & D, specifically
has been weakened so it can replicate in the during stability
body several times and generate an immune studies.
response without causing the disease, e.g.
chickenpox, measles, mumps and rubella,
rotavirus, and shingles vaccine viruses. The
BCG vaccine contains live weakened
tuberculosis bacteria.
After immunisation, the weakened vaccine
viruses or bacteria replicate (grow) in the
vaccinated person. This means a relatively
small dose of virus or bacteria can be given in
order to stimulate an immune response.
Live attenuated vaccines do not usually cause
disease in vaccine recipients who have a
healthy immune system. If a live attenuated
vaccine does cause disease, e.g. chickenpox
disease from the vaccine virus, it is usually
more mild than disease caught from another

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, Mumbai 1
 B.Pharm. Industrial Training
Daily Report
person in the community.
If administered to a person who has an
impaired immune system response, e.g. they
have leukaemia or HIV infection, or are taking
immunosuppressing medications,
administration of a live attenuated vaccine
may cause severe disease as a result of
uncontrolled replication (growth) of the
vaccine virus.

Inactivated or dead vaccines

Inactivated vaccines do not contain live
viruses or bacteria. Viruses in these vaccines
are inactivated or split, e.g. polio or
influenza vaccines in New Zealand, and
bacteria killed. New Zealand does not have a
killed bacteria vaccine on the Immunisation
Schedule, but a travel-related vaccine is
available for purchase. They cannot cause the
disease but the inclusion of adjuvants
(immune enhancers) in the vaccine help
generate an immune response.
These types of vaccine can be safely given to
a person with an impaired immune system
response. However, a person with an
impaired immune system response may not
develop the same amount of protection after
immunisation as a healthy person receiving
the vaccine.
Inactivated vaccines usually require multiple
doses. Some inactivated vaccines may also
require periodic supplemental doses to
increase, or ‘boost’ protection against
disease.
Hepatitis A, influenza and polio vaccines are
inactivated virus vaccines on the New
Zealand Immunisation Schedule.

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Subunit vaccines
These vaccines present proteins or sugars
derived from the disease-causing organism.

Protein vaccines
Protein vaccines may includee fragments
extracted from a virus or bacteria such as
inactivated bacterial toxoid proteins,
e.g. tetanus and diphtheria vaccines, or be
engineered without the disease-causing
organism, e.g. virus-like particles in hepatitis
B and human papillomavirus (HPV) vaccines.
Protein vaccines may also include bacterial
sugar/carbohydrate (polysaccharide)
molecules that are joined (conjugated)
to proteins, e.g. Haemophilus influenzae type
b (Hib), meningococcal and pneumococcal
conjugate vaccines. The immune system of
infants and young children is not able to
generate a useful immune response to the
sugar molecules on these bacteria, which is
one reason why their risk of disease and
complications is so high. Joining (conjugating)
each sugar molecule to a protein helps their
immune system can generate a protective
immune response. These vaccines also
generate an excellent immune response in
adults. Protein vaccines cannot cause the
disease and the inclusion of adjuvants in
some vaccines help generate an immune
response.

Pure polysaccharide vaccines

Some vaccines only include
sugar/carbohydrate (polysaccharide)
molecules found on the outside of
some bacteria, e.g. some vaccines to protect

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 B.Pharm. Industrial Training
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against pneumococcal or typhoid disease.
This type of vaccine can generate a
protective immune response in older children
and adults and cannot cause the disease.

Nucleic acid-based vaccines

At present, different types of nucleic-acid
vaccines are in developmental, pre-clinical
and clinical evaluation phases, e.g.
for prevention of human immunodeficiency
virus (HIV), influenza and malaria diseases
and treat some cancers. This vaccine
platform is also being used to develop
vaccines to prevent COVID-19 disease.
Nucleic acid-based vaccines use the hosts
own cell machinery to make the antigen,
which is then presented to the
immune system. While RNA is encapsulated
into lipid nanoparticle and injected, DNA is
fired directly in the host cells using a
brief electrical pulse.

RNA vaccines

o Unlike a normal vaccine, RNA vaccines

work by introducing an mRNA
sequence (the molecule which tells
cells what to build) which is coded for
a disease specific antigen, once
produced within the body, the
antigen is recognised by the immune
system, preparing it to fight the real
thing
o RNA vaccines are faster and cheaper
to produce than traditional vaccines,
and a RNA based vaccine is also safer
for the patient, as they are not
produced using infectious elements

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o Production of RNA vaccines is
laboratory based, and the process
could be standardised and scaled,
allowing quick responses to large
outbreaks and epidemics
o Most current research is into RNA
vaccines for infectious diseases and
cancer, for which there are several
early-stage clinical trials, there is also
some early research into the potential
of RNA vaccines for allergies

11:45- FDA plays a critical role in protecting the This knowledge is

12:30 United States (U.S.) from threats such as very useful and to
emerging infectious diseases, including the be applied during R
Coronavirus Disease 2019 (COVID-19) & D, specifically
pandemic. FDA is committed to providing during stability
timely guidance to support response efforts studies
to this pandemic. FDA is issuing this guidance
to provide sponsors of requests for
Emergency Use Authorization (EUA) for
COVID-19 vaccines with recommendations
regarding the data and information needed
to support the issuance of an EUA under
section 564 of the FD&C Act (21 U.S.C.
360bbb-3) for an investigational vaccine to
prevent COVID-19 for the duration of the
COVID-19 public health emergency. This
document supersedes the guidance of the
same title issued in February 2021 (which
superseded the guidance of the same title
issued October 2020).
been named “SARS-CoV-2” and the disease it
causes has been named “Coronavirus Disease
2019” (COVID-19). On January 31, 2020, HHS
issued a declaration of a public health

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 B.Pharm. Industrial Training
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emergency related to COVID-19 and
mobilized the Operating Divisions of HHS.1 In
addition, on March 13, 2020, there was a
Presidential declaration of a national
emergency in response to COVID-19.2 The
SARS-CoV-2 pandemic presents an
extraordinary challenge to global health.
There are currently no FDA-licensed vaccines
to prevent COVID-19. Commercial vaccine
manufacturers and other entities are
developing COVID-19 vaccine candidates
using different technologies including RNA,
DNA, protein, and viral vectored vaccines.
This guidance was first developed prior to
issuance of a EUA for a COVID-19 vaccine and
takes into account the EUAs currently in
place for COVID-19 vaccines. This guidance
describes FDA’s current recommendations
regarding the data and information needed
to support the issuance of an Emergency Use
Authorization (EUA) under section 564 of the
FD&C Act (21 U.S.C. 360bbb-3) for an
investigational vaccine to prevent COVID-19,
including chemistry, manufacturing, and
controls information (CMC); nonclinical data
and information; and clinical data and
information, as well as administrative and
regulatory information.

12:30- Live attenuated vaccine This knowledge is

1:30 An attenuated vaccine (or a live attenuated very useful and to
vaccine) is of a, but still keeping it viable (or be applied during R
"live"). Attenuation takes an infectious agent & D, specifically
and alters it so that it becomes harmless or during stability
less virulent. These vaccines contrast to those studies

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produced by "killing" the virus
Attenuated vaccines stimulate a strong and
effective immune response that is long-
lasting. In comparison to inactivated
vaccines, attenuated vaccines produce a
stronger and more durable immune response
with a quick immunity onset. Attenuated
vaccines function by encouraging the body to
create Common examples of live attenuated
vaccines are vaccines.

Cell-based vaccine production process

The cell-based vaccine manufacturing
process uses animal cells (Madin-Darby
Canine Kidney, or MDCK cells) as a host for
the growing flu viruses instead of fertilized
chicken eggs. For the 2020-2021 season, the
viruses provided to the manufacturer to be
grown in cell culture are cell-derived rather
than egg-derived.

Large scale vaccine production

How a vaccine is approved for production

For more information on the three phases of
vaccine clinical trials, .
Once a vaccine has reached pre-approval
stage following clinical trials, it is assessed by
the relevant regulatory body for compliance
with quality, safety and efficacy criteria.
Following regulatory approval,
manufacturers can submit a vaccine to WHO
for (PQ), an assessment process that ensures
quality, safety and efficacy and helps the UN
and other international procurement
organizations determine the programmatic
suitability of a vaccine. During global health
emergencies, the (EUL) may be used to allow

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emergency use of the vaccine. The EUL exists
because, in a pandemic situation, products
that could benefit the lives of people all over
the world may be prevented from coming to
market with sufficient speed. The EUL is a
fast-tracked but rigorous process, designed
to bring impactful products to all those in
need, as quickly as possible, on a time-limited
basis and based on a risk-versus-benefit
evaluation. The WHO PQ/EUL
recommendation may be used by UN
agencies such as UNICEF and the Pan
American Health Organization Revolving
Fund for procurement decisions in low- and
middle-income countries. Gavi also relies on
WHO EUL/PQ to specify which vaccines its
funds may be used to purchase.

How it’s made

Typically, companies will work independently
to complete clinical development plans for a
vaccine. Once a vaccine is authorized,
manufacturing begins to scale up. is
weakened or deactivated. To form the full
vaccine, are combined.
The whole process, from preclinical trial to
manufacture, can sometimes take over a
decade to complete. In the search for a
COVID-19 vaccine, researchers and
developers are working on several different
phases in parallel, to speed up results. It is
the scale of the financial and political
commitments to the development of a
vaccine that has allowed this accelerated
development to take place. Also, nations and
international health organizations are
working together through to invest in
development capacity upfront to streamline

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the process, as well as to ensure equitable
distribution of vaccines.

How it’s packaged

Once the vaccine has been made in bulk
quantities’, it is bottled in glass vials and then
carefully packaged for safe cold storage and
transport.
Vaccine packaging must be able to withstand
extreme temperatures, as well as the risks
involved in being transported globally.
Therefore, vaccine vials are most commonly
made from glass, as it is durable and able to
maintain its integrity in extreme
temperatures.

How it’s stored

When a vaccine is too hot or too cold, it
becomes less effective or even inactive. If
stored at the incorrect temperature, vaccines
can be ruined or unsafe for use. Most
vaccines require refrigerated storage at
between 2 and 8 °C. Some vaccines require
temperatures as cold as -20°C. Some of the
newer vaccines need to be kept ultra-cold at
-70°C. For frozen vaccines some of them can
be safely stored for a limited time between 2
and 8°C.
Regular refrigerators cannot maintain an
even temperature consistently, so specialized
medical refrigerators are required for these
precious products.

How it’s shipped

To maintain this cold chain, vaccines are
shipped using specialized equipment that
does not compromise the integrity of the
product. Once shipments land in the

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destination country, refrigerated lorries
transport the vaccines from the airport to the
warehouse cold room. From there, portable
iceboxes are used to transport vaccines from
the cold room to regional centres where
they’re stored in refrigerators. If vaccination
takes place outside of the regional facility,
the final step often requires portable
iceboxes to transport the goods to local areas
for vaccination campaigns. New technologies
have invented some portable devices that
can keep vaccines at their cold temperature
for several days without needing electricity.

Quality control
Once vaccines start being administered,
national authorities and WHO constantly
monitor for – and establish the severity of –
any possible adverse side effects and
responses from people who have received
the vaccine. The safety of the vaccine is
paramount, with regular assessments and
post-approval clinical studies to report on its
safety and effectiveness.
Studies are often conducted to determine
how long a given vaccine remains protective.

2:30 – Vaccine: A Transition Affair from Academia This knowledge is

4:00 To Industry very useful and to
be applied during R
What are the ingredients in a vaccine? & D, specifically
Vaccines contain tiny fragments of the during stability
disease-causing organism or the blueprints studies
for making the tiny fragments. They also

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contain other ingredients to keep the vaccine
safe and effective. These latter ingredients
are included in most vaccines and have been
used for decades in billions of doses of
vaccine.
Each vaccine component serves a specific
purpose, and each ingredient is tested in the
manufacturing process. All ingredients are
tested for safety.

Antigen
All vaccines contain an active component
(the antigen) which generates an immune
response, or the blueprint for making the
active component. The antigen may be a
small part of the disease-causing organism,
like a protein or sugar, or it may be the whole
organism in a weakened or inactive form.

Preservatives
Preservatives prevent the vaccine from
becoming contaminated once the vial has
been opened, if it will be used for vaccinating
more than one person. Some vaccines don’t
have preservatives because they are stored
in one-dose vials and are discarded after the
single dose is administered. The most
commonly used preservative is 2-
phenoxyethanol. It has been used for many
years in a number of vaccines, is used in a
range of baby care products and is safe for
use in vaccines, as it has little toxicity in
humans.
Stabilizers
Stabilizers prevent chemical reactions from
occurring within the vaccine and keep the
vaccine components from sticking to the
vaccine vial.

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Stabilizers can be sugars (lactose, sucrose),
amino acids (glycine), gelatin, and proteins
(recombinant human albumin, derived from
yeast).

Developing a vaccine generally involves years

of research. First, we need a vaccine
candidate that is evaluated in animals for its
safety and efficacy. After a vaccine candidate
passes a pre- clinical trial, it enters the clinical
trial phase. While scientists have worked
round the clock in the laboratory, even
regulatory approvals which used to take
several months have been fast tracked. It
helped eliminate all the time lapses between
the pre-clinical and clinical trial stages.
Earlier, the vaccine development involved a
series of steps, but in the case of the
coronavirus vaccine, the scientists and
regulators worked in tandem, accelerating
the whole process without compromises on
any protocols and any step.
Data shows Moderna and Pfizer vaccines,
which both use the same mRNA technology
to create immunity against the novel
coronavirus, remain effective after 6 months.
Still, Pfizer officials in February said they are
testing a booster shot up to a year after a
person receives their first two doses.

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