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 “arguably the most important public health development in the history of humankind. Over the last 200 years it has saved hundreds of millions of lives worldwide”[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.
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Clinical trials 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[3]. 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.[4]
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 July 2011.
2 CMO Annual Report 2008. Avaliable at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/AnnualReports/DH_096206; accessed July 2011.
3 Department of Health. Immunisation against Infectious Disease. Chapter 9 Surveillance and monitoring for vaccine safety. Available at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_079917; accessed July 2011.
4 MHRA How we regulate. Periodic Safety Update reports http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/PeriodicSafetyUpdateReports/index.htm#1; accessed July 2011
UK VACCINE INDUSTRY GROUP