Vaccine quality control

Metz B, Hendriksen C F M, Jiskoot W, Kersten G F A (2002). Rednction of animal use in human vaccine quality control Opportunities and problems. Vaccine. 20 2411-2430. 

In current practice the fluorescence assay is often followed by the use of hybridization techniques when more selectivity is required. We have for instance used the fluorescence techniques to obtain data on the nucleic acid content of malaria vaccine proteins produced in Escherichia coli. The rapid turnaround time of the fluorescence assay is particularly useful during the early stages of purification to determine the optimal process conditions. After the final process has been arrived at and a variety of methods used to assess the nucleic acid content (including the hybridization techniques), the fluorescence method can be developed for routine quality-control purposes. In certain cases, particularly at high protein concentrations, the dye may bind to the protein with... 

The quality control of vaccines is intended to provide assurances of both the effieacy and the safety of every batch of every product. It is executed in three ways ... 

The results of all quality control tests are always recorded in detail as, in those eountries in which the manufacture of vaccines is regulated by law, they are part of the evidence on which control authorities judge the suitability or otherwise of each batch of each preparation. 

The quality control of both diphtheria and tetanus vaccines requires that the products are tested for the presence of free toxin, that is for specific toxicity due to inadequate detoxification with formalin, at the final-product stage. By this stage, however, the toxoid concentrates used in the preparation of the vaccines have been much diluted and, as the volume ofvaccine that can be inoculated into the test animals (guinea-pigs)... 

There is the potential to develop a protective vaccine/immunization programme for each and every infectious disease. Whether or not such vaccines are developed and deployed is related to the severity and economic impact of the disease upon the eommunity as well as the effects upon the individual. Principles of immunity and of the produetion and quality control of immunological products are discussed in Chapters 14 and 15, respeetively. 

NMR can also be used to elucidate the structural features of a repeating unit in a polysaccharide and to investigate the conformation and dynamics of polysaccharides.21 A unique polysaccharide structure results in a characteristic proton NMR spectrum. Therefore, NMR is a powerful tool for identifying polysaccharide structures. This remarkable specificity has led to the development of a routine NMR-based identity assay, recently reported by Abeygunawardana et al. for quality control testing of bacterial polysaccharide to be used in formulating a polyvalent pneumococcal polysaccharide vaccine.22... 

ANALYTICAL ASSAYS AND QUALITY CONTROL OF EXCIPIENTS FOR VACCINE FORMULATIONS... 

Microparticulate Systems for the Delivery of Proteins and Vaccines, edited by Smadar Cohen and Howard Bernstein Good Manufacturing Practices for Pharmaceuticals A Plan for Total Quality Control, Fourth Edition, Revised and Expanded, Sidney H. Willig and James R. Stoker... 

Precise definition of the host-protection epitope(s) of the Taenia and Echinococcus vaccine antigens would be valuable if it were to lead to the development of a synthetic vaccine or provide reagents to assist with quality control of vaccine production. Identification of a limited number of host-protective fragments may allow the recombinant antigen to be replaced by synthetic peptides. This would have significant advantages in the production... 

After purification, lyophilize the peptide constructs and check their purity on analytical HPLC and MALDI-TOF mass spectroscopy. The conventional matrix for peptide mass spectroscopy, a-cyano-4-hydroxycinnamic acid, appears to work properly for the vaccine constructs. While it is less frequently used in standard peptide chemistry (and thus not detailed here), the size of these multiple peptide antigens allows quality control by SDS-PAGE as shown in Fig. 2. For this purpose we recommend the use of 16.5% precast peptide gels. These gels tend to break easily, so be careful during gel handling. 

As well as these general criteria there may be specific tests appropriate to specific products with regard to quality control. Therefore, each product s production and quality control should be considered independently, taking into account any special characteristic. The considerations for each product must also relate to its clinical use. Therefore, a preparation to be administered repeatedly over a long period of time or in large doses will probably need to be subjected to more stringent tests (particularly for antigenicity) than a product that is applied only once (e.g. a vaccine). 

The chemistry of the effect of formaldehyde in the tanning process probably is related closely to its action in the production of toxoids (6). This procedure was developed in the first part of this century mainly by trial and error and still thrives today. Toxins are treated with formaldehyde for several weeks at temperatures close to 40°C. This results in the toxin being changed in such a manner that it retains its capacity to elicit an immune response when injected into an animal or person but it lacks the capacity for the specific and damaging attack that is associated with the native toxin. Imprecise as this procedure seems today, the satisfactory results obtained through strict quality control have resulted in its continuing use and the production of many millions of doses of life-saving vaccines. However, more specific modifications should be available for such purposes from current research. 

Cell-based vaccines EMEA points to consider on the manufacture and quality control of human somatic cell therapy medicinal products 2001... 

No adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine. Therefore preclinical and toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/ vaccine combination [60], Evaluation in preclinical studies is important for identifying the optimum composition and formulation process and also for allowing development of tests for quality control [61]. Data from these studies also helps plan protocols for subsequent clinical trials from which safety and efficacy in humans can be evaluated. 

Therefore quality control (QC) testing of vaccines normally includes the following assays, which must be passed prior to material being released for use in preclinical toxicology studies sterility, endotoxin, general safety, identity, mass, potency, purity, and stability [62], These assays should be performed on the final product using the clinical formulation. 

Robinson [48] described a gas chromatographic method for measuring residual water in freeze-dried smallpox vaccine in 1972. The method was developed to optimize quality control of a tissue-culture smallpox vaccine. Water is extracted from the sample with benzene and determined by gas chromatography with thermal conductivity (hot wire) detection and columns packed with Chromosorb 102. 

Castle, P. Policy and progress of the european pharmacopeia in the use of alternatives of animal testing in vaccine production and quality control. In Alternatives to Animal Testing in the Production and Quality Control of Vaccines Present Practice and Prospectives RIVM Bilthoven, 1992 41-52. 

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