ABOUT VACCINES
Value of Vaccines
The World Health Organization (WHO)
estimates that vaccine-preventable diseases are responsible for a
quarter of the 10 million deaths occurring annually among children
under five years of age[1] . In the UK, the Chief Medical Officer
described vaccines as “probably the most successful public health
measure of all time [as] they continue to protect children and many
adults around the world from serious illness, disability and premature
death”[2] .
Principles of vaccination
Vaccination is
the administration of a killed or modified microorganism, or a
substance from the microorganism, in order to prevent disease. The
principle of vaccination is based on a natural response within the
human body, known as immunity. Immunity is the ability of the body to
tolerate the presence of its own ‘native’ material, such as blood,
organs and gut bacteria, and to eliminate ‘foreign’ material from
outside the body. This ability to discriminate is the basis of
protection against infectious diseases.
Infectious diseases are
illnesses caused by microorganisms, the collective term for bacteria,
fungi, parasites and viruses. When we catch a disease, our bodies
usually respond by producing specific proteins, called antibodies, to
fight the disease-causing organism. After recovery, these specific
antibodies remain at low levels in the blood and bone marrow. If we
come into contact with this microorganism again, our immune system
remembers the organism and rapidly produces antibodies to it,
preventing the disease process so that we can remain healthy. This type
of protection arises from so-called ‘active immunity’ and is normally
permanent. In other words, we only have to have some diseases once to
be protected all our lives if we come into contact with exactly the
same organism again. This phenomenon is called immunological memory.
Vaccination
mimics the active immune process without our bodies actually
experiencing the disease. When vaccine particles enter the blood
stream, the body sees them as potentially disease-causing organisms.
The immune system is then stimulated to produce antibodies, as
described above, providing us with protection against any future
contact with the ‘real’ organism. Vaccines produce a similar
immunological memory, after one or several doses, to that following the
naturally acquired disease without having to risk suffering the
complications of the disease.
‘Forgotten’ diseases
The
success of vaccination has become, to some extent, its downfall.
Successful vaccination programmes have reduced the incidence of many
common childhood diseases globally, and almost completely eradicated or
dramatically reduced them in the UK, for example polio, diphtheria,
whooping cough, measles and mumps. Once a disease “disappears”, its
burden can be quickly forgotten. Unfortunately, unless completely
eradicated, infectious diseases have a tendency to return. The UK has
witnessed several outbreaks of vaccine preventable diseases, such as
whooping cough (pertussis) and measles, each time there is a dip in the
number of children vaccinated.
Successful vaccination can only
be achieved in the UK if it has the support of the public, the
Government and the NHS, and if a supportive environment is maintained.
Vaccine development
Vaccine
development is a long process, taking on average 10-12 years from test
tube to patient. The safety of a product that will be used in millions
of healthy individuals is of paramount importance. Even after the
regulatory bodies have granted marketing authorisation (a licence),
continued surveillance programmes ensure that the vaccine is effective
and well tolerated.
| Clinical trials Clinical trials determine whether a drug should be licensed and which population groups it should be recommended in. Trials are conducted in phases, each having a different purpose and answering different questions: In Phase I trials researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. In Phase II trials the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. In Phase III trials the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. A drug is usually licensed based on Phase III trials. In Phase IV trials after a drug has been licensed - post marketing studies delineate additional information including the drug's risks, benefits, and optimal use. Source: http://clinicaltrials.gov |
Vaccine production
Vaccines are difficult to produce and
the processes are time consuming. There are careful controls in
production and very strict quality control processes to guarantee the
safety and efficacy of the vaccines produced.
How are vaccines made?
Vaccines
are made in several different ways depending on the microorganism which
is being used and the way in which it needs to be grown. The processes
also change according to the type of vaccine which is being produced -
viral or bacterial, live or inactivated.
Since viruses are
parasites which can only grow in living cells, viral vaccines are
produced in live cell cultures. The process for many viral vaccines
begins with almost laboratory scale culture and is progressively scaled
up to larger and larger culture vessels. Each one of these steps takes
a finite time and cannot be accelerated.
The viruses for some
other viral vaccines are grown in hen's eggs. Production planning needs
to take this into account when placing orders for the eggs.
Bacterial vaccines are produced in a very similar way with production
being scaled up in volume over a period of time.
Following the
growth phase the microorganisms need to be further treated to produce
the vaccine. This could involve inactivation or splitting into smaller
units and purification. This produces what is referred to as the
vaccine ‘bulk’.
Quality assurance
Vaccine bulk needs
to be quality assured for purity, safety and potency. For example, to
determine that the correct organism has grown and not changed during
the growth period, the vaccine is potent enough, it is free of
contamination and it contains the correct ingredients in the correct
amounts.
If the vaccine that is being produced has more than one
constituent e.g. the combined measles, mumps and rubella (MMR) vaccine,
the next stage is to blend the bulks to produce the final vaccine.
Further testing is carried out to ensure there is no interference
between the individual components of the vaccine.
To produce a
bulk lot of a vaccine can take up to a year if there are no hitches. If
any of the tests have to be repeated the production time increases.
Prior
to marketing approval of a new vaccine, three consecutive batches of a
completed product are evaluated to ensure consistency of production.
The finished product
The
finished vaccine is put into appropriate containers which could be
ampoules, vials or syringes. It is again tested to make sure it
conforms to the product licence, for example that is has the correct
potency, sterility, volume and pH. This process can take four to ten
weeks.
Samples of the bulk and finished product are sent one of
several European Official Medicines Control Agencies so that they can
repeat the tests and satisfy themselves that the vaccine is suitable
for use. This can take up to two months. Only after the vaccine is
approved for use in the marketplace will the manufacturers pack it in
the appropriate packaging and ship it to the distribution points.
Producing,
testing and delivering batches of vaccine from bulk can take five to
seven months. The total production period for a vaccine can take almost
twenty months from raw ingredients to the final vaccine actually being
available to the end user.
Vaccine safety
All vaccines
are extensively tested by their manufacturers for quality, purity,
safety, and efficacy before a product licence can be granted[3].
In addition, the manufacturers must submit samples of each vaccine
batch together with the results of their own potency, safety and purity
tests for independent assessment before the batch can be released for
general use.
In the UK, the Vigilance Risk Management of the
Medicines Division of the Medicines and Healthcare Products Regulatory
Agency (MHRA) has responsibility for monitoring the safety of all
medicines, including vaccines[3]. The MHRA uses a variety of methods to
collect information on medicines. Healthcare professionals and patients
are encouraged to report suspected adverse drug reactions and there is
a legal requirement for companies to report such reactions to their
products to the MHRA[4]. When a vaccine is first marketed, it undergoes
intensive monitoring and all adverse events must be reported. Reports
of suspected adverse reactions are classified and entered into a
national register operated by the MHRA[3].
The number, pattern
and severity of reported reactions are regularly reviewed and
appropriate investigation and action is initiated if a possible problem
is identified. Important information on vaccine safety is routinely
collected through spontaneous adverse drug reaction reporting schemes
such as the Yellow Card scheme, information from pharmaceutical
companies, and information from worldwide regulatory authorities. All
vaccine companies produce regular global summaries of all adverse
events. This Periodic Safety Update Report (PSUR) is sent to all local
regulatory authorities for review.[5]
1
WHO Sixty-first World Health Assembly provisional agenda item
11.17: Global Immunization Strategy, 3 April 2008. Available at: http://apps.who.int/gb/ebwha/pdf_files/A61/A61_10-en.pdf. Accessed 13 August 2009
2 CMO Annual Report 2007
3
Immunisation against Infectious Disease. Surveillance and
monitoring for vaccine safety Chapter updated August 2006. Department
of Health. http://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/Greenbook/fs/en Accessed October 2006
4 MHRA Safety Information. How we monitor the safety of products. http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=273 Accessed October 2006
5 MHRA How we regulate. Periodic Safety Update reports http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=686 Accessed October 2006
UK VACCINE INDUSTRY GROUP