2. Vaccines are preparation that induce immune response
Vaccines for human use may contain whole microorganismsor that have been
treated to attenuate their virulence whilst retaining adequate immunogenic
properties; antigens extracted from microorganisms or secreted by
microorganisms or produced by genetic engineering or chemical synthesis
Vaccines may contain an adjuvant where the antigen is adsorbed on a mineral
adjuvant, the vaccine is referred to as “adsorbed”.
5. These are preparations of live bacteria, viruses or other agents which, when
administered by an appropriate route, cause subclinical or mild infections. In the
course of such an infection the components of the microorganisms in the vaccine
evoke an immune response which provides protection against the more serious
natural disease. Examples: Vaccinia (Smallpox), BCG (TB)
6. Killed vaccines are suspensions of bacteria, viruses or other pathogenic agents,
that have been killed by heat or by disinfectants such as phenol, ethanol or
formaldehyde.
Killed organisms cannot replicate and cause an infection. Thus every dose of killed
vaccine must have an antigenic material to increase the immunogenic response.
7. Since all the components of the microorganism are present, it may be toxic to the
body.
Thus it is recommended to divide the vaccine into booster doses which may be
given at regular intervals of time.
Examples: Polio, Typhoid, Pertussis, Cholera, Plague, Rabies.
8. Heterogeneous collection of substances which enhance the immune response.
Examples: Aluminium hydroxide gel (hydrated aluminium oxide) and aluminium
phosphate are the only ones in general use in human vaccines.
9. Toxoid vaccines are preparations derived from the toxins that are secreted by
certain species of bacteria.
In the manufacture of such vaccines, the toxin is separated and treated chemically
(Formaldehyde) to eliminate toxicity but not immunogenicity.
This process is called as toxoiding and the end product is termed as Toxoid or
Formol toxoids.
11. Instead of using whole cells which may consist of undesirable reactogenic
components, vaccines are prepared from purified protective components.
These vaccines evoke an immune response only to the component, or components,
in the vaccine and thus induce a response that is more specific and effective.
Examples: Hemophilus influenzae type b, Neisseria meningitidis ACWY, Hepatitis
b etc.
12. Some antigens which are used to prepare vaccines are less immunogenic and do
not give appropriate responses.
Such antigens are conjugated to certain immunogenic carriers which improve the
immunogenic response.
Example: Glyco- Conjugate Vaccine of Neisseria meningitidis with carrier protein
is CRM197
13. Vaccines can be considered as an extraordinary group of biologics.
They are heterogeneous with respect to composition (e.g., live-attenuated,
polysaccharide and many others) and, in most cases, they are not ‘well defined’.
Each vaccine needs a tailor-made set of tests in order to establish its quality. The
current regulatory requirements for a biopharmaceutical products are well
summarized in three ICH guidelines: Q7, Q8 and Q9.
14. Because a high product quality requires the identification of critical process
parameters and definition of the design space, it will be clear that identifying the
product quality attributes and the development of assays that provide this
information are essential for process development of biopharmaceuticals.
15. The availability of a panel of high-quality assays in the development stage of a
vaccine can reduce the risk of failure during clinical trials.
When the product is licensed, the number of tests is reduced, because the
production process is validated and consistent production has been demonstrated.
16. For live-attenuated viral vaccine assays, measuring the number of infectious
particles and the level of impurities is important.
In the case of a recombinant protein, assays may be crucial to address chemical
and conformational stability, aggregation and the presence of post-translational
modifications, at least during the development phase.
17. Studies designed to determine the rate of change of vaccine properties over time as a
consequence of the exposure to temperatures higher than those recommended for
storage. These studies may provide useful support data for establishing the shelf-life
or release specifications but should not be used to forecast real time real condition
stability of a vaccine. They could also provide preliminary information on the vaccine
stability at early developmental stages and assist in assessing stability profile of a
vaccine after manufacturing changes.
18. Parameters that are direct or indirect indicators of vaccine efficacy or safety
demonstrated in clinical trials. They are used to assess product suitability
throughout the shelf-life. Determination of these parameters should result in
quantitative values with the detectable rate of change. Qualitative parameters
such as sterility could also be considered but cannot be included in the statistical
analysis.
19. Studies performed to determine the impact of extreme environmental factors such
as light and extreme temperature. These studies are not usually performed as
part of a stability program, but are used instead to establish protective packaging
and container conditions, and to support exclusionary labeling.
20. Typically a vaccine production process takes place as follows:
