Therapeutic equivalence defined

On the other hand, biopharmaceuticals are difficult to characterize. Therefore under certain conditions a product may be defined by its manufacturing process, and the final product may be linked to a specific process. Additionally, it is challenging -both in scientific and regulatory terms - to determine if complex dmg substances are comparable before and after manufacturing changes, or to decide if they are therapeutically equivalent when made by different companies. 

Boddy et al. [7] defined the Therapeutic Availability as the ratio of the rate of input of free drug divided by that of the drug carrier for the same degree of maximal therapeutic effect. When considering steady-state conditions, this definition is equivalent to that shown in Eq. 13.20 and 13.21. 

Hunt et al. [6] demonstrated that the DTI is also equivalent to the ratio of the therapeutic index (abbreviated to TI in Hunt et al. s paper in this chapter TI is defined differently, see Section 13.4.3) of the drug-carrier conjugate and that of the free drug. The therapeutic index (also called the therapeutic ratio) is a statistical measure defined as the ratio of the median toxic dose to the median effective dose [22]. 

Key CPZ equiv dose = Chlorpromazine equivalent dose.This concept is of value in comparing the potency of classical antipsychotics. Dose ranges are not specified as they are extremely wide and drugs are normally titrated up from low starting doses (e.g. chlorpromazine 25 mg or equivalent) until an adequate antipsychotic effect is achieved or the maximum dose reached.The chlorpromazine equivalent dose concept is of less value for atypical antipsychotics since minimum effective doses (Min. eff. dose) and narrower therapeutic ranges have been defined. Maximum dose (Max. dose) can be exceeded only under specialist supervision. 

The methodology for establishing equivalence between pharmaceutical products by means of a clinical trial in patients with a therapeutic end-point has not yet evolved as extensively as for pharmacokinetic bioequivalence trials. However, some important items which need to be defined in the protocol can be identified. 

Standardized extracts If the constituents with known therapeutic activity are known, the equivalent quantity or the ratio of the herbal substance to the herbal preparation shall be stated and the quantity of the herbal preparation may be given as a range corresponding to a defined quantity of these constituents (see example) or... 

Bioequivalence (BE) is defined as the similarity in the rate and extent of therapeutic and toxic effects observed by the administration of equivalent doses of the pharmaceutical formulations or pharmaceutical alternatives, under similar conditions. It is estimated by comparing the analytical and the above-mentioned pharmacokinetic parameters at different doses for the pharmaceutical preparation under study. 

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