Product potency tests

Product Potency Tests. Two assays were developed that measure the potency of the FGF-4 protein. In the first case, a one-step growth promotion assay is conducted on normal, human retinal pigment epithelial cells (ARPE-19). The assay measures metabolic activity (Alamar blue dye metabolism) after infection of ARPE-19 cells with a serial dilution of the drug substance (Ad5FGF-4). The increase in metabolic activity correlated with FGF-4 protein production (determined by an FGF-4 ELISA), increased de novo DNA synthesis (measured by BrdU incorporation), and an increase in cell number. 

Standardization and Testing". RequHemeats are geaerally specified within Hceases Hi the United States, and include a variety of Hi-process tests to assess purity, safety, and potency of the iadividual components and potency and safety of the final product. Potency is standardized by determining the size of the conjugate and the quantitative amount of saccharide that is bound to the carrier protein. General safety and immunogenicity is assessed Hi animals. 

Edgren carried out a number of studies in which bioassays were used to compare the widely differing potencies of a number of analogues of 17/i-oestradiol that were modified in the 18-position. Commenting on the use of potency ratios, Edgren concluded that they were only valid for specific substances and test systems and useless for product safety testing . These problems could have important consequences for any attempt to establish the potency of specific environmental EDs or environmentally relevant mixtures. 

Drug substance/drug product purity, potency, and other testing Drug substance/drug product stability testing Method development, validation, and transfer Drug product formulation development... 

After the product has been filled (and sealed) in its final product container. QC personnel then remove representative samples of the product and carry out tests to ensure conformance to final product specification. The most important specifications will relate to product potency, sterility and final volume fill, as well as the absence of endotoxin or other potentially toxic substances. Detection and quantification of excipients added will also be undertaken. Product analysis is considered in Chapter 7. 

All pharmaceutical finished products undergo rigorous QC testing in order to confirm their conformance to predetermined specifications. Potency testing is of obvious importance, ensuring that the drug will be efficacious when administered to the patient. A prominent aspect of safety testing entails analysis of product for the presence of various potential contaminants. 

The identity, purity, potency and stability of the final bulk product are established initially by carrying out a wide range of chemical, physical, immunochemical and biological tests. Prior to release, each batch of the product is tested by the by the manufacturer for identity and purity... 

The same process that will be used for commercial-scale production should be adopted to produce the material used in the preclinical and clinical trials. Significant differences in the production process used to obtain this material can invalidate the clinical trial results for the commercial product, unless the comparability is demonstrated by identity, purity, stability, and potency tests (ICH, 1998b). 

Several assays to characterize the final product with respect to titer, purity, identity, potency, particle to infectious ratio, and stability are listed in Table 2.3. In addition, vector product safety testing should be conducted prior to animal or human studies. Assays used for product characterization and safety testing are included in Table 2.3. 

Topicals are intended for use on human skin. Therefore, they should be tested on a suitable surface. Many studies on topicals have used hard surface carriers, or even suspension tests, and extrapolated the results on product potency to human skin. We do not believe this to be a valid approach because skin may present a greater challenge than a hard inanimate surface [26] and a much greater challenge than suspension tests. Mucous membranes may present an even greater challenge. 

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