Vaccine production quality control

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 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. 

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... 

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. 

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. 

Use in the production of vaccines As assay organisms to determine antibiotic, vitamin and amino acid concentrations Quality control of immunological products Assay methods Sterilization methods Sterilization monitoring and validation procedures Sterility testing Assessment and calculation of sterility assurance Aseptic manufacture... 

From the basic chemical industry come raw materials to use in large-scale formulation of the new product. From the vast fermentation vats come antibiotics. In laboratory-like formulation facilities, the mixing, baking, compressing, coating, and other pharmaceutical processes take place, under the watchful eye of quality control inspectors. In the space-age-clean rooms of biological production, virus vaccines are grown, harvested, purified, and endlessly tested. From start to finish, statistical, numerical, procedural, physical, chemical, and analytical control systems attempt to reduce to near-zero the potential error, mixup, distortion, or hazard. 

The health status of animals from which starting materials are derived and of those used for quality control and safety testing should be monitored and recorded. Staff employed in animal quarters must be provided with special clothing, changing facilities and showers. Where monkeys are used for the production or quality control of biological products, special consideration is required, as laid down in the revised Requirements for Biological Substances No. 7 (Requirements for Polio-myelitis Vaccine (Oral))(5). 

Animals are used for the manufacture of a number of biological products for example polio vaccine (monkeys), snake antivenoms (horses and goats), rabies vaccine (rabbits, mice and hamsters) and serum gonadotropin (horses). In addition, animals may also be used in the quality control of most sera and vaccines, e.g., pertussis vaccine (mice), pyrogenicity (rabbits), BCG vaccine (guinea-pigs). 

Summary - There are several advantages to vaccines derived from recombinant DNA technology 1) there is a potential for higher margin of safety 2) the products may be less expensive due to savings related to production methods, stability, and quality control 3) it should be possible to produce vaccines for diseases not amenable to current technology 4) some of these products can be incorporated into formulations not possible with the currently available materials and 5) since many of the methods required to develop these vaccines were beyond the technology of the time, it should be possible to develop proprietary vaccine products. 

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