PHARMACOLOGY be highly sound , and has been used to bring numerous generic medications onto the market over the last 40 years , with no proof existing that a generic is inferior when used for its registered indication . The science is so sound , that the innovator company also relies on the same methodology when they want to change their formulation e . g . when a tablet is changed to a palatable tablet , bioequivalence testing is used to save on costs and prevent retesting as once again , there is no need to repeat all the tests . All in all , if a generic formulation is registered and the company follows GMP , there should be no difference between a generic and an innovator .
Nonetheless an important concept in generic medication development is the concept of switchability and prescribability .
• Generics are interchangeable and any of the registered formulation for a particular species can be considered a valid effective choice at the start or initiation of treatment in a patient . This is known as prescribability i . e . the choice is open when the drug is first prescribed .
• However this scenario changes when one is treating a chronic condition where the patient has been stabilised on treatment with a particular formulation e . g . epilepsy . Under these conditions , it is not advisable to switch formulations acutely ( irrespective of whether it a generic or innovator ) acutely . This acute switching can only occur if the products are tested for switchability , which most formations are not e . g . one can chose to use formulation A or formulation B initially ( at this stage there is no difference ). However at the end of the month , stick to the same formulation and don ’ t change acutely as this can be dangerous and result in destabilisation ( i . e . for chronic patients , stock the same formulation ). If you do need to change formulation , it ’ s always safer to phase out the old formulation while the new formulation is phased in .
• Compounded formulations : These are formulations that are meant for use in an individual patient and are tailor made drugs , usually made by a pharmacist on an “ as needed ” basis . Compounded formulations are generally simple formulations with the active dispersed in an excipient . These compounded products , due to their individualised nature , don ’ t need to legally comply with GMP requirements , and thus may be open to all the problems mentioned above . For this reason , the use of compounded products from a safety point to the patient and consumer , should not be used when there are alternate registered products i . e . legally one takes responsibility for the use . More importantly , it may be more difficult legally to demonstrate that the use of the compounded product use was prudent when there are GMP approved alternates available . Also of importance to consider is the product ’ s sterility and purity and shelf life . Since this may be a problem , compounded products should ideally be limited to oral or topical use ; and they should not be used in production animals .
Is a Generic , definitely a generic ?
This may seem as an odd question , in light of what has been said above . But it ' s important to know the constraints of the process of bioequivalence . The foremost principle of bioequivalence is the comparison of the plasma profile between the test and reference product , and show that they ’ re essentially identical . However as mentioned under pharmacokinetics , the PK of a drug is dependent on a number of factors such as absorption and elimination . This would mean that the profile is dependent on the species of testing and the metabolism of the drug . As such , when bioequivalence is shown , each profile has to be determined for each the different route recommended and in each of the different species it is indicated for . As an example , a drug recommended for use by the subcutaneous and intramuscular in pigs , cattle and horses , will need to be tested in six separate studies to show that all the routes per species are bioequivalent . Since it may not always be possible demonstrate bioequivalence in all these studies , some generic formulations will have curtailed claims . As such it is important to check what the recommendation are on the package instead of assuming that they are the same as the innovator ( reference product ).
Another important consideration is the use of human medication in animals . Firstly this extra-label use of the drugs has legal implications , as the person recommending this use , takes responsibility if something goes wrong ( for registered veterinary drugs used correctly as stated on the package insert , the registration owner takes responsibility ). The use of human drug extra-label is nonetheless considered safer than using a compounded product , as good manufacturing practice is still in place as it ’ s a registered human product ( i . e . same liability , but lower risk ) ( Table 2 ).
As a veterinarian , it is incumbent on you to make use of your professional judgement when choosing to use a human formulation . Firstly consideration must be given to the dose , which means that one needs to take into consideration the studies that have demonstrated that this extra-label use is prudent . For the latter consideration needs to be given to the sample size , as registered product use a substantial number of clinical cases to prove that the effect is real ( as large as a few hundred animals ) i . e . the published study on extra-label use may only have included a small number of clinical cases and not taken into consideration intra-subject variability in effect and side effects . Another important consideration would be that the product used in the publication , may not necessarily be the same product that is sold locally e . g . There are numerous cases of companies choosing to market different formulations in different countries for various manufacturing reasons even though the name is the same . It is possible that the published formulation may have a different response to the South African available drug , purely because they are of different formulation .
Issue 03 | JUNE 2017 | 19