Bioequivalency therapeutic equivalence

More important than bioequivalence is the therapeutic equivalence of LT4 products. Will patients have the same outcomes if bioequivalent products are used The study by Dong... 

Brand interchange - The metolazone formulations are not bioequivalent or therapeutically equivalent at the same doses. Mykrox is more rapidly and completely bioavailable. Do not interchange brands. 

Bioequivalency The sprinkle formulation is bioequivalent to the immediate-release tablet formulation and, therefore, may be substituted as therapeutically equivalent. 

Bioequivalence problems have been documented in the past for products marketed by different manufacturers however, studies in patients have shown comparable clinical efficacy between brands based on the results of thyroid function tests brand interchange should be limited to products with demonstrated therapeutic equivalence... 

Equivalence trials are, of course, routinely used in the evaluation of bioequivalence and the methodology there is well established, both European and FDA guidelines exist. More recently we have seen the need to establish therapeutic equivalence and Ebbutt and Frith (1998) provide a detailed case study in the development of an alternative propellant for the asthma inhaler. More usually,... 

The rules for therapeutic equivalence are different from those for bioequivalence. The choice of margin will be a mixture of statistical and clinical reasoning. Strict equivalence is appropriate when we want to consider essential similarity or where the test treatment is to be used as an exact replacement for the new treatment. In these cases A should be chosen to be a completely irrelevant difference from a clinical point of view. Ebbutt and Frith (1998) based their choice of A= 15l/min on several considerations ... 

Therapeutic equivalence - If two or more drugs produce the same therapeutic effect or the same toxicity they are therapeutically equivalent. Note that they might not be bioequivalent. 

In an effort to codify bioequivalence information, the FDA publishes Approved Drug Products With Therapeutic Equivalence Evaluations, with monthly supplements, commonly called "the Orange Book." The book contains listings of multisource products in one of two categories Products coded "A" are considered bioequivalent to all other versions of that product with a similar "A" coding. Products not considered bioequivalent are coded "B." Of the approximately 8000 products listed, 90% are coded "A."... 

That documentation of pharmaceutical- and bio-equivalence should be provided to regulatory authorities is not at issue. However, the means by which these data can and should be demonstrated remain the subject of discussion. Political, economic and scientific hurdles pervade, and this issue remains unresolved. The imposition of existing small-molecule equivalence criteria on the registration of generic biologic drug products is unlikely to provide an acceptable degree of consumer protection. Likewise, the conventional bioequivalence trial used to infer therapeutic equivalence of different formulations based on the similarity of the phar-... 

Generic products tested by the FDA and determined to be therapeutic equivalents are listed by the FDA in their publication Approved Drug Products with Therapeutic Equivalence Evaluations. These products contain the same active ingredients as their brand-name counterparts and also meet bioequivalence standards. The FDA recommends substitution only among products listed as therapeutically equivalent. 

Two similar drugs are therapeutically equivalent if they have comparable efficacy and safety. [Note Clinical effectiveness often depends both on maximum serum drug concentrations and the time after administration required to reach peak concentration. Therefore, two drugs that are bioequivalent may not be therapeutically equivalent.]... 

Biogenerics per se, that is, protein drug products approved via 505(j)(l), would need to demonstrate their bioequivalence to the innovator protein. Flowever, due to their complexity and heterogeneity, the classical biopharmaceutical principles upon which the current ratings of therapeutic equivalence are based do not apply in their current language to complex macromolecules. For example, due to the nature and complexity of an immunogenic response, one concern would be if traditional bioequivalence appropriately addresses the complex safety issues associated with biologies. 

Pharmaceutical alternatives are drug products that contain the same therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form. Drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling. Although pharmaceutical alternatives may ultimately be proven bioequivalent, given their differences they are not automatically presumed to be. 

The Waxman-Hatch Act of 1984 was motivated, to a significant degree, by cost considerations, but quality issues concerning bioequivalency and therapeutic equivalency were addressed as well. All FDA-approved drugs (pioneer brand-name and generic versions) are required to meet the same FDA standards of quality. 

Although thera-peutic equivalence is assured if two formulations are bioequivalent, the therapeutic equivalence of two bioinequivalent formulations can be judged only within a specific clinical context (23). Thus, if we ordinarily treat streptococcal throat infections with a 10-fold excess of penicillin, a formulation having half the bioavailability of the usual formulation would be therapeutically equivalent, since it still would provide a 5-fold excess of antibiotic. 

Ethinyloestradiol (EE) Ortho Evra patch Abdomen application is not bioequivalent, but therapeutically equivalent to that applied at the other sites. ... 

To ensure interchangeability, the multisource product must be therapeutically equivalent to the comparator product. Types of in vivo bioequivalence studies include pharmacokinetic studies, pharmacodynamic studies and comparative clinical trials. Direct practical demonstration of therapeutic equivalence in a clinical study usually requires large numbers of patients. Such studies in humans can be financially daunting, are often unnecessary and may be unethical. For these reasons the science of bioequivalence testing has been developed over the last 40 years. According to the tenets of this science, therapeutic equivalence can be assured when the multisource product is both pharmaceutically equivalent/alternative and bioequivalent. Assuming that in the same subject an essentially similar plasma concentration time course will result in essentially similar concentrations at the site(s) of action and thus an essentially similar therapeutic outcome, pharmacokinetic data may be used instead of therapeutic results. In selected cases, in vitro comparison of dissolution profile of the multisource product with that of the comparator product, or dissolution studies, may be sufficient to provide indication of equivalence. 

Products are pharmaceutical alternative(s) if they contain the same molar amount of the same active pharmaceutical moiety(s) but differ in dosage form (e.g. tablets versus capsules), and/or chemical form (e.g. different salts, different esters). Pharmaceutical alternatives deliver the same active moiety by the same route of administration but are otherwise not pharmaceutically equivalent. They may or may not be bioequivalent or therapeutically equivalent to the comparator product. 

Two pharmaceutical products are considered to be therapeutically equivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and after administration in the same molar dose, their effects, with respect to both efficacy and safety, are essentially the same when administered to patients by the same route under the conditions specified in the labelling. This can be demonstrated by appropriate bioequivalence studies, such as pharmacokinetic, pharmacodynamic, clinical or in vitro studies. 

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