Vaccine production potency

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

The single-component bacterial vaccines are listed in Table 15.1. For each vaccine, notes are provided of the basic material fkm which the vaccine is made, the salient production processes and tests for potency and for safety. The multicomponent vaccines that are made by blending together two or more of the single component vaccines are required to meet the potency and safety requirements for each of the single components that they contain. The best known of the combined bacterial vaccines is the adsorbed diphtheria, tetanus and pertussis vaccine (DTPerWac/Ads) that is used to immunize infants, and the adsorbed diphtheria and tetanus vaccine (DTWac/Ads) that is used to reinforce the immunity of school entrants. 

The same name is also being used for some vaccines that differ in potency. As shown in Table 1.4, the two approved vaccines against hepatitis B, Recombivax HB and Engerix-B, both known as Hepatitis B Vaccine (Recombinant), when used as directed, are therapeutically equivalent in terms of their ability to induce antibodies that protect vaccinated individuals from hepatitis B virus infection. However, the dose and volume required to produce a satisfactory immune response are different for each product and for each age group. 

Unlike the analogous attenuated malaria sporozoite vaccine (Hoffman et a/., 2002), the schistosome counterpart has not been tested in humans but our recent demonstration of protection in a small-scale chimpanzee trial (Eberl et a/., 2001) attests to its potential as a basis for the development of a recombinant vaccine. However, attempts to replicate the success of the attenuated schistosome vaccine by administration of recombinant antigens have had only limited success. It is notable that, faced with similar problems in replacing the attenuated malaria vaccine with recombinant antigens, it is now proposed to develop a cryopreserved product that meets regulatory, potency and safety requirements, for use in humans (Luke and Hoffman, 2003). 

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. 

Center for Biologies Evaluation and Research (CBER) The branch of the FDA responsible for the regulation of biological products, including blood, vaccines, therapeutics and related drugs and devices, to ensure purity, potency, safety, availability and effectiveness, www.fda.gov/cber... 

Vaccines containing killed microorganisms or their products are generally tested for potency in assays in which the amount of the vaccine that is required to protect animals from a defined challenge dose of... 

The Biological Standards Act (1975) established the National Biological Standards Board. This Board, appointed by the UK health ministers and funded by the Health Department, is responsible for standards and control of biological substances, that is substances whose purity and potency cannot be adequately tested by chemical means, such as hormones, blood products and vaccines. The Board operates through the executive arm, the National Institute for Biological Standards and Control. 

The remaining vaccinia vaccine licensed in the United States (Dryvax, manufactured by Wyeth, Philadelphia, Pa.) is a live, infectious virus prepared from calf lymph. Like all smallpox vaccines that were marketed in the United States, it derived from the NYCBOH strain and contains 108 plaque-forming units per milliliter. Current vaccinia vaccine stocks (> 12 million doses) are held by the CDC. It must be noted that the potency of several lots of this lyophilized vaccine has fallen. Pharmaceutical companies in the United States lack interest in manufacturing new lots of vaccine, owing to the absence of a profitable retail market, antiquation of calf-lymph production techniques and facilities, and the manufacturer s legal liability for vaccination complications. 

The FDA was given authority to approve these products as both safe and effective and to require certification that each batch or lot conforms to the established standards of purity and potency. The regulation of biological products (serum, vaccines and blood products) began in 1944 with the Public Health Service Act and was supplemented in 1986 by the Childhood Vaccine Act, which required patient information on vaccines, and gave the FDA authority to recall biologies and authorized penalties for violations. 

For a very long time, freeze-drying has been essentially concerned with the preservation of unstable biochemicals and, more particularly, of injectables. The very first issue was, then, to secure their sterility and safeguard then-potency during processing, storage, and reconstitution. At the outset most products were freeze-dried as such, either as a natural substance, such are blood plasma, biosynthetic isolates, or antibiotics, or, else, for vaccines. 

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