Generic drugs/products drug substance

Bioavailahility studies are used to compare different formulations of the drug product, or different batches of the same formulation and, as discussed in Chapter 8, generic copies of a reference drug. Their comparative value is based on the premise that, if similar amounts of identical active substance are delivered to the site of action at similar rates, then a similar biological response can be expected, which leads to the conclusion that the two preparations are bioequivalent. 

The BCS also predicts the possibility of obtaining an in vitro/in vivo correlation. Justification of a biowaiver is based on a combination of the BCS classification of the drug substance and a drug product dissolution profile comparison. In all these instances, an anchor with a bioavailable product is established. Specifically, to obtain a biowaiver for an IR generic product ... 

A preservative is a substance that prevents or inhibits microbial growth and extends the shelf life of the drug products. In most pharmaceutical drug products, only a few compounds are typically selected as preservatives. For efficiency, a generic method should be developed for the types of preservatives that are more commonly used. For example, butylated hydroxytoluene (BHT) is an antioxidant commonly used in many solid dosage formulations to retard oxidative degradation of the excipients. 

The generic representation in Figure 1 illustrates the various types of impurities that may arise during the production of a dosage form. It is not all inclusive, as each dosage form has unique sources of impurities, but it includes most of the important ones. The sources of impurities increase with the increase in the number of components and the number of steps in the process. Each drug substance and excipient has its own impurity profile and the potential for interactions and reactions. 

The most widely used method of challenging the legitimacy of the process used to manufacture the generic product is to undertake an impurity profile study of the drug substance extracted from the competing product, in short to check its impurity fingerprint vs. your own product. Most companies can describe cases. One in my experience occurred when an Italian company decided to market Amikacin, at that time a patented Bristol-Myers product, in Korea. 

The preformulation study tasks for the generic products are simpler than those for the original prescription products. By the time the generic product is marketed, the innovative drug product may have been sold for a long time. Most of the preformulation data and information have been published and can be found in publications such as the Analytical Profile for Drug Substances and Excipients and in the United States Pharmacopeia (USP) and foreign pharmacopoeia. 

A preservative is a substance that extends the shelf-life of drug products by preventing oxidation or inhibiting microbial growth.14 Preservatives must be monitored in the products since they are considered to be active components. Generic HPLC assays are typically developed for preservatives such as buty-lated hydroxytoluene (BHT), an antioxidant for solid dosage forms, and antimicrobials such as parabens, sodium benzoate, or sorbic acid in liquid formulations. For these additive components, typical assay specifications are 85-115% of label claim. 

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