1. Which studies and controls have to be performed before vaccines can be authorised and marketed?
Vaccines must have a very good safety profile, because most vaccines are administered to healthy individuals who, depending on their level of exposure, may only have a small risk of contracting an infection even when they are not vaccinated. Because of the high demands on the manufacture and analytical controls, modern vaccines have a good tolerability profile, and adverse drug reactions are rare. Vaccine manufacturers have to adhere to strictly defined manufacturing processes that fulfil both international guidelines and the requirements of the European Pharmacopoeia.
In addition to animal studies, which provide initial evidence not only in terms of the immunogenicity (benefit) but also in terms of the tolerability (risk) of a given vaccine, the marketing authorisation of vaccines is based on comprehensive clinical studies in humans that comply with any legal and scientific requirements. The number of participants in such clinical studies varies between 1000 and 70 000, depending on whether the vaccine is already well known (e.g., tetanus) or whether it is highly innovative (e.g., rotavirus). National competent authorities are responsible for weighing the benefits of a given vaccine (i.e., its potential to prevent a disease) against its risks (i.e., its potential side effects). A marketing authorisation is granted only if the ‘benefit-risk ratio’ is positive, i.e., if the benefits are found to outweigh the risks.
2. What does "batch release" mean?
Before a batch of vaccines is allowed to be marketed in Austria, it has to undergo tests by the Official Medicines Control Laboratory (OMCL) of a EU/EWR member state. The results of the tests must comply with the specifications stipulated during marketing authorisation. If the results do not comply, the batch cannot be marketed in Austria.
The protocols for batch manufacturing and testing are checked for each batch. Additionally, test samples are submitted for analysis as stipulated during marketing authorisation.
Vaccines holding a Europe-wide marketing authorisation and cleared by another OMCLs, can be marketed in Austria based on mutual recognition of batch release (notification) after the application and certificate of batch release have been verified.
3. Does AGES provide individual vaccination advice?
No. As official Medicines Agency, AGES can merely provide information about which vaccines MAY be used. However, the agency cannot give any advice on which vaccines SHOULD be used. This decision is at the discretion of the physician.
Current vaccination recommendation (Impfplan) of the Austrian Ministry of Health is available at: http://bmg.gv.at/home/Schwerpunkte/Praevention/Impfen/
4. Where can I find the Summaries of Product Characteristics (SmPCs) and Package Leaflets (PLs) of individual vaccines?
SmPCs and PLs in German language are available at the Austrian Medicinal Product Index.
5. What is the difference between inactivated and live vaccines?
Inactivated vaccines contain bacteria, viruses, toxins or their components in an inactive form. These inactivated disease-causing pathogens cannot cause symptoms of the disease they would usually be associated with. However, the immune response they trigger is mostly weaker than with live vaccines. Some inactivated vaccines use specific additives to allow for a better immune response. Inactivated vaccines usually cannot provide life-long immunity and booster- or additional doses of the vaccine are needed to maintain the immune response.
Live attenuated vaccines contain modified strains of pathogens (bacteria or viruses) that have been weakened but are able to multiply within the body and remain antigenic enough to induce a strong immune response.
Examples of live vaccines are vaccines against mumps, measles, rubella, varicella (chickenpox), herpes zoster (shingles), yellow fever and rotaviruses. Influenza and typhoid vaccines are usually inactivated vaccines, but live attenuated vaccines for these have also been authorised for marketing.
6. Could the vaccine manufacturing process lead to impurities that may cause diseases such as bovine spongiform encephalopathy (BSE) or acquired immunodeficiency syndrome (AIDS)?
Certain cell culture systems used for virus propagation use foetal calf serum. However, bovine products have to be certified and derived from BSE-free countries (e.g., New Zealand). Human albumin, a protein derived from the plasma of human donors and contained as stabilizer in a small number of vaccines, is also subject to stringent testing.
Human albumin is routinely tested for the presence of pathogens, such as human immunodeficiency virus (HIV) or hepatitis virus. In addition, the manufacturing process of human albumin contains specific virus inactivation steps rendering ineffective any viruses that may have gone undetected during routine testing.
7. Is it true, that some vaccines are produced using components derived from human fetuses?
The antigens for only 3 vaccines - rubella, varicella (chickenpox) and Hepatitis A - are grown in cell cultures that were originally obtained from two human fetuses.
The cell cultures were developed in the 60s and have been growing under laboratory conditions for more than 45 years.
Manufacturing biological medications such as vaccines is a highly complex process, made difficult by the fact that viruses cannot reproduce on their own. They require a living host in which to grow, such as chicken embryos or cells from animals or humans that are grown in culture.
Cell lines can be differentiated as being primary cell lines (consisting of cells taken directly from living tissue, e.g chicken fibroblast cells), diploid cell lines or continuous cell lines. They are grown in cell banks and can be preserved at -70 °C or in liquid nitrogen stores for very long periods of time. For vaccine manufacture, tiny amounts of cell culture are extracted from the stores and propagated until sufficient amounts of cells have grown to provide a biological system in which the viruses can be cultivated.
Two different strains of human diploid cell cultures made from fetuses have been used extensively for vaccine production for decades: one is MRC-5, developed from lung cells from a healthy 14-week-old male fetus in 1966; the other is WI-38, which was developed came from lung cells taken from a female fetus of 3-months gestation. The abortions were not conducted for the purpose of vaccine discovery or vaccine production.
8. Do vaccines contain mercury?
Mercury is a ubiquitous element and can be found in soil, air and water. It can enter the food chain as methylmercury, and is biomagnified in aquatic food chains. High amounts of methylmercury can harm the nervous system.
Thimerosal (ethylmercury) is a mercury-containing organic compound and has been used as a preservative in inactivated vaccines for decades. Ethylmercury is formed when the body breaks down thimerosal and is broken down and cleared out of the blood more quickly than methylmercury. Low-level ethylmercury exposures from vaccines are very different from long-term methylmercury exposures, since the ethylmercury does not stay in the body.
Nowadays only a small number of vaccines contain thimerosal, e.g. the vaccine for influenza pandemics Pandemrix ©. Preservatives have become close to redundant due to single-dose injectables and sterile filling during production. As a precaution, vaccine manufacturers have stopped using thimerosal as a preservative in vaccines for children.
9. Which section of the Summaries of Product Characteristics (SmPCs) and Package Leaflets (PLs) provides information on the substances contained in a vaccine?
After downloading the Summary of Product Characteristics (SmPCs) and Package Leaflet (PLs) from the Austrian Medicinal Product Index (German language only), the following sections provide information on the composition of the vaccine:
Section 2. Qualitative and quantitative composition:
Contains information on the antigen, the substrate used for propagation of the antigen (e.g. cell line, embryonated eggs), adjuvant and preservative, if present.
Section 4.3. Contraindications; 4.4. Special warnings and precautions for use: Contain information on manufacturing residues (e.g. formaldehyde, antibiotics, egg protein etc.). Barely-quantifiable residues of these substances may be present in the vaccine, but their declaration is important to people suffering from certain allergies.
Section 6.1. List of excipients: all other ingredients as water, stabilisers, salts or buffer solutions.
The same information is contained in sections 2. “What you need to know before you <take> <use> X “ and 6. “Contents of the pack and other information “ of the product information leaflet.
10. What is the difference between vaccines for children carrying the addition ‘Junior’ in their names (e.g., TBE vaccines) and the corresponding vaccines for adults?
Vaccines for children carry the addition ‘Junior’ and differ from their adult counterparts only in that they contain different filling volumes. Vaccines for children contain half the dose of adult vaccines, but their composition is the same.
Examples of vaccines for which both a children’s and an adult version are available are the TBE vaccines FSME-Immun® and Encepur®, the hepatitis A vaccine Havrix®, the hepatitis B vaccine Engerix®, the hepatitis A + B combination vaccine Twinrix®, or the influenza vaccine Vaxigrip®.
For both the children’s and adult formulations, data providing evidence not only for the efficacy but also for the tolerability in the targeted age group are evaluated.
11. How are vaccines stored properly?
Storage recommendations are detailed in the Summary of Product Characteristics (SmPCs) and Patient Information Leaflet (PILs) of each product. To ensure the viability of the vaccine, make sure the recommendations on how to store the vaccine have been followed at all times.
Inactivated vaccines (for which the cold chain does not have to be maintained) can be stored outside the refrigerator for short periods of time. Temperatures above +25°C and direct sunlight should be avoided.
It is important to maintain the cold chain for live attenuated vaccines, including during transport (eg. from the pharmacy to you home, or to the doctor’s surgery). Consider using an isolated container and cold packs.
Generally, vaccines should be protected from direct light and freezing, and should be stored between +2 °C and +8 °C. Vaccines should always be stored in trays in the middle of the refrigerator, never in the doors (vaccine frequently exposed to warmer temperatures when the door is opened) or right at the back of the refrigerator (risk of freezing).
During transport, make sure frozen cool packs are not directly in contact with the vaccines to avoid freezing.
12. Does vaccination provide 100 per cent protection against the disease it is intended to prevent?
No vaccination guarantees 100 per cent protection of vaccinated individuals—just as there is no medicinal product that is effective in 100 per cent of treated individuals.
The reasons for this are differences in the individual immune response, which is influenced by personal factors, such as age, sex, or pre-existing disease. Other essential aspects are the correct handling of the vaccine and its administration in accordance with the recommended vaccination schedule.
13. Can vaccines be administered during pregnancy and breast-feeding?
As a general rule, dead vaccines, such as tetanus, pertussis, and influenza (i.e., influenza caused by the influenza virus), can be administered during pregnancy.
Live vaccines, such as those against measles, mumps, and rubella, are contraindicated during pregnancy, even though there has not been any documented case of damage to an unborn child as a result of an inadvertently administered rubella vaccination.
Generally speaking, all vaccinations can be administered during breast-feeding.
However, please be sure to refer to the Summary of Product Characteristics (SmPC) and Package Leaflet (PL) for specific information on the use of vaccines during breast-feeding. See also Question 4, ‘Where can I find the Summaries of Product Characteristics (SmPCs) and Package Leaflets (PLs) of individual vaccines?’.
14. Which side effects may occur after vaccination?
Possible side effects are listed in the Summary of Product Characteristics (SmPC) and Package Leaflet (PL) of each individual vaccine, sorted by type of side effect and frequency of occurrence.
See also Question 4, ‘Where can I find the Summaries of Product Characteristics (SmPCs) and Package Leaflets (PLs) of individual vaccines?’
15. Does aluminium contained in vaccines pose a risk?
Aluminium (usually aluminium hydroxide and/or aluminium phosphate) has been used as an adjuvant in several vaccines (e.g. FSME, diphtheria, tetanus, whooping cough and hepatitis vaccines), as it helps to improve the immune response to the antigen. Live attenuated vaccines, e.g. mumps, measles, rubella, chickenpox and rotavirus vaccines, generally do not contain aluminium compounds.
Aluminium has been used widely for almost 90 years as an adjuvant.
Vaccinations are, in comparison to the whole span of a life-time, a relatively rare event. Also, as most vaccines do not contain aluminium, the body burden of aluminium following injections of vaccines containing aluminium adjuvants has been classified as being negligible.
The amount of aluminium per injected dose is strictly controlled, and must not exceed 1,25mg per dose in accordance with the European Pharmacopoeia.
The WHO reviewed safety data available for aluminium-containing vaccines, the report can be downloaded.
The German Paul Ehrlich Institute (PEI) also published a report (in German language only) on the safety of for aluminium-containing vaccines.
To date, pharmacovigilance data support the clinical trial and epidemiological evidence of the safety of aluminium in vaccines and no urgent need has been identified necessitating the ban of aluminium-containing compounds as adjuvants from medicinal products.
All in Austria marketed medicinal products containing aluminium compounds have packaging information listing all active substances and excipients contained in the vaccine.
To address the recurring question of the safety of aluminium in medicinal products, the AGES has published the following information (in German) on its homepage, which can be downloaded.
Created: 23.10.2011 | Page last modified: 13.09.2019