Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
The Quality and Safety Requirements for Vaccines with Emphasis on Viral Vaccines from a Global Point of View
Michael Zlottchenko (Abschlußjahr: 2010)
Language: English
Immunization is one of the most successful and cost-effective health interventions ever. The benefit of vaccination has been demonstrated for vaccines, both at individual as well as community level. An important challenge of immunisation is to ensure vaccines quality and safety. Vaccines differ from chemical drugs in that they can not normally be characterised molecularly; starting materials such as bacteria, viruses, or genetically modified microorganisms are of enormous complexity, as well as having the capacity to vary from preparation to preparation. The quality and safety of a vaccine preparation can not be assured solely by testing the end-product, but depends on the strict control of the manufacturing process following the principles of good manufacturing practice. These include characterisation of starting materials (use of cell banking and seed lot systems is strongly encouraged), demonstration of production consistency through process validation and enhanced pre- and post-market surveillance of vaccines. In addition to the general strategies to ensure safety and quality of vaccines outlined above particular consideration may be necessary to address specific safety concerns associated with particular product types. Regulatory requirements for vaccines and other biologicals are provided by the following regulatory bodies such as:
- International Conference on Harmonisation (ICH)
- European Agency for the Evaluation of Medicinal Products (EMEA)
- US Center for Biologics Evaluation and Research (CBER)
- World Health Organisation (WHO)
In addition, pharmacopoeial requirements, such as those of the European Pharmacopoeia, Pharmacopoeia of United States are also established for specific vaccines. Viral vaccines are considered to be a heterogeneous class of medicinal products containing immunogenic substances capable of inducing specific, active and protective host immunity against viral diseases.
Viral vaccines may include one or more of the following:
- Inactivated / killed viruse
- Attenuated virus
- Protein subunit of virus
- DNA Vaccine
The production of drug substance, unformulated active (immunogenic) substance must have been shown to yield consistently batches. It begins with the choice of strain and establishment of a seed lot system involving a master seed lot and working seed lot. The virus strain shall be identified as being suitable which shall include information on the origin of the strain and its subsequent manipulation. Genetic stability should be confirmed and a testing program to control it should be established based on the current regulatory requirements. Different cell substrates might be used for production of the virus including primary cells, diploidcell lines and embryonated hens eggs. If animal or human-cell substrates are used in production of vaccine it is important to ensure the absence of contaminating viruses. Where materials of ruminant origin are used compliance with TSE guidelines is required. Safety of a vaccine may be effected by substances that are intended to be part of the final formulation (e.g. adjuvant, preservative, stabilizers) and substances that are used in the manufacturing process of final formulation and may be presented in the final formulation in residual amounts (e.g. formaldehyde, toxins, viral growth media/substrate).
Stability evaluation is a vital part of the assessment of the vaccine quality and safety. The purpose of stability studies is to ensure that the vaccine at the end of its shelf life still has the required characteristics supporting quality, safety and efficacy. Vaccines are large and complex molecular assemblies that are highly susceptible to environmental factors that may significantly affect their activity. A major problem in assessing vaccine stability is the fact that many vaccines possess a specific biological activity that cannot be fully characterised by physicochemical methods alone. Therefore biological assays play an important role in the quality control of vaccines and are essential parameters of vaccine quality.
An additional important tool for monitoring safety of vaccines is post-marketing surveillance. The objectives of pharmacovigilance for vaccines are to identify rare or new adverse events, identify those that are causally related to the vaccine /vaccination and estimate their rate of occurrence. Vaccines are different from most other medicinal products in way that they are a preventive measure, usually given to healthy individuals and especially young children at vulnerable age. No immediate health benefit might be apparent to the individual patient. The risk-benefit balance for vaccines depends on risks for the healthy vaccinee and the benefits for that individual as well as the whole population.
Pages: 34