Generic drugs certainly represent an opportunity for the costs of the healthcare system. However, if their use is not managed appropriately by limiting substitutability even between generics, there may be cases of therapeutic inequivalence which can nullify savings.
As is known, generic medicines are "copies" of the "original" medicines which can be placed on the market after the expiry of the original product's patent at a lower cost. This aspect represents the main purpose of introducing generics into the drug distribution cycle and the lower cost is justified by the fact that the companies that produce them have not had to bear the costs of research and development, while they only bear the costs! of production and distribution.
The composition from the original may differ in the chemical form (salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance) and in the excipients. Furthermore, the therapeutic indications may be different between the original drug and its generic counterpart due to the European registration process which reflects the indications of the starting State of the registration request.
Given that the generic drug can have different chemical forms and excipients from the corresponding originator, in order to obtain registration it is necessary to demonstrate that the two preparations are bioequivalent from a pharmacokinetic point of view, i.e. that the absorption and exposure to the drug are similar.
The two formulations are defined as bioequivalent if the difference between pharmacokinetic parameters falls within a conventionally fixed range of ± 0.20%.
This gives rise to the so-called "bio-creep" phenomenon which can compromise substitutability. For example, assuming one generic has +15% bioavailability and a second generic -13%, both are bioequivalent to the standard they mimic, but are not bioequivalent to each other.
Unfortunately, direct comparison is not possible as generic medicines are only compared with the original medicine, and so interchangeability between generics is only assumed. Problems can arise not so much in the acute use of a drug but in the substitution of more generic ones in the course of chronic therapies.
Francis Scaglione
University of Milan
March 13, 2013 – DoctorNews33
