Pharmaceutically equivalent products

For situations (b), (c), (e), (f) and (g) above, it is incumbent upon the applicant to demonstrate that the excipients in the pharmaceutically equivalent product are essentially the same and in concentrations comparable to those in the comparator product or, where applicable (i.e. (e) and (g)), that their use is not expected to affect the safety and/or efficacy of the product. In the event that this information cannot be provided by the applicant and the drug regulatory authority does not have access to the relevant data, it is incumbent upon the applicant to perform appropriate studies to demonstrate that differences in excipients or devices do not affect product performance. 

Drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which ... 

Drug products that FDA at this time does not consider to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which actual or potential bioequivalence problems have not been resolved by adequate evidence of bioequivalence. Often the problem is with specific dosage forms rather than with the active ingredients. These are designated BC, BD, BE, BN, BP, BR, BS, BT, or BX. (25)... 

Bioequivalence means that two or more chemically or pharmaceutically equivalent products produce comparable bioavailability characteristics in any individual when administered in equivalent dosage regimen (parameters compared include the area under the plasma concentration versus time curve (AUC) from time zero to infinity (AUC)q, maximum plasma concentration and the time of peak concentration). 

Figure 7.5 A plot of plasma concentration (Cp) versus time data following the administration of a dose of a drug as chemically or pharmaceutically equivalent products (identical dosage forms). One of these (the reference product) must be an innovator product.

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

For dmgs approved originally between 1938 and 1962, the FDA has utilized the Abbreviated New Dmg AppHcation (ANDA) for review of generic products that are pharmaceutical equivalents of the initially approved products. In this way, costiy dupHcation of animal and human experimentation is avoided. The new manufacturer has to show only that its manufacturing methodology, specifications, quaUty control, and labeling are acceptable. In some cases, the FDA does require proof of bioequivalence. 

The influence of RP on selling prices depends on the monopsony power of the buyer, the price elasticity of the product and the cross-price elasticity for substitute products, and also the coverage of products under RP. The situation most likely to result in equivalence between RP and price-cap regulation is when there is a majority buyer, the number of products under RP is very large and demand is very elastic. In general, the RP system attains its objectives best when the pharmaceutical bill has a close relationship with price pressure and when price differentials in the market for equivalent products are high, which has clear links with the presence of generics. 

There are three levels of equivalence for classifying products, each submitted to an identical maximum level of public financing chemical equivalence, pharmacological equivalence and therapeutic equivalence. The first level entails establishing groups for the same active ingredient, which at the same time include both generics and brand-name pharmaceuticals whose patent has expired. This is the system applied in Sweden, Denmark, Norway and Spain. It encompasses bio-equivalent products with identical qualitative or quantitative composition, pharmaceutical form, dose, administration method and presentation . 

Another collateral effect of the DESI project was the development of the abbreviated NDA, by which a generic version of the innovator product could satisfy the statutory preconditions for entering the market, without repeating the preclinical and clinical studies of the innovator. This administrative creation, designed to assure that generics were both pharmaceutically equivalent and bioequivalent to the pioneer product, was endorsed by Congress in 1984. As will be seen, this development had a staggering impact on the business model of the pharma industry. 

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