Are generic drugs as effective as brand-name drugs when the excipients are different?
A medicine comprises an active principle (sometimes several) and excipients (substances without therapeutic activity that give the treatment's shape, taste, and color).
To be considered a generic drug, a drug must contain strictly the same amount of the same active ingredient as the original drug. On the other hand, the excipients may differ. When designing a generic drug, the excipients are chosen so that the latter has the same amount of active ingredient released at the same rate in the body as the original drug. The bioequivalence trials make it possible to ensure this and thus ensure that the generic drug has the same therapeutic effects as the original drug.
Indeed, excipients of a generic drug are not always the same as the brand-name drug. In some cases, the differences of excipients between the generic drug and original drug can be a plus for intolerant or allergic people, especially when the generic drug is designed without the excipient with known effect present in the original medicine.
In any case, scientific studies conducted in recent years on thousands of patients treated for different diseases prove that generic drugs are as effective as original drugs and do not have more side effects.
Do generic drugs benefit from the same controls as brand-name drugs? Aren't there fewer clinical trials?
Before being marketed, a generic drug must, like any drug, obtain a Marketing Authorization. The MA file for a generic drug must include all the elements that demonstrate the pharmaceutical quality of the medicine and its bioequivalence with the original specialty. The generic molecule product is not reassessed given that it has already shown its efficacy and safety: it has already benefited from around ten years of studies before its marketing and the MA application for the original medicinal product, and at less than ten years of real-life use.
The molecule, including clinical trials. The MA file for the generic drug thus refers to the studies carried out by the laboratory of the original prescription to demonstrate the efficacy and safety of the use of the drug. Moreover, the generic drug must provide proof of its pharmaceutical quality and its bioequivalence with the original medicinal product (biopharmaceutical dossier) to guarantee identical therapeutic efficacy and safety in use.
What is the content (stages and criteria) for validating the transition to generic status?
To obtain the quality of a "generic" drug, a drug must submit a biopharmaceutical dossier including studies (called "bioequivalence trials") demonstrating its bioequivalence with the original medication.
This step, necessary to obtain a marketing authorization (AMM) issued by the National Agency for the Safety of Medicines and Health Products (ANSM), is essential because the bioequivalence guarantees efficacy and safety of use identical to those of the original drug.
What are clinical or biological tests carried out for generic drugs, in particular for excipients?
To be considered a generic drug, a drug must contain strictly the same amount of the same active ingredient as the original drug.
On the other hand, the excipients may differ: when designing a generic drug, the excipients are chosen so that the latter has the same amount of active ingredient released at the same rate in the body as the original drug.
The bioequivalence trials make it possible to ensure this and thus guarantee that the manufacturing processes and excipients do not call into question the efficacy and safety of the molecule. Therefore, the tests of bioequivalence are made on the drug in its final form.
The generic drug must also prove its quality by validating its manufacturing and control method. If (and only if) efficacy, safety, and quality are guaranteed, the generic drug obtains a marketing authorization (MA).
Compared to the typical drug, what percentage of effectiveness does a generic drug obtain a marketing authorization?
The statistical comparison between generic drugs and originator drugs involves two parameters: average area under the curve (AUC) and maximum blood concentration (Cmax). The ratio of means is calculated, and its 90% confidence interval, that is to say, the gap in which the actual value of the balance has nine chances out of 10 to be found.
The bioequivalence is demonstrated if the confidence interval [CI90] of the ratio (generic drug/originator drug) of the mean AUCs and Cmax is entirely between 80 and 125%.
This interval [80% - 125%] has been defined internationally by considering that a variation of the ratio of means up to 20% has only a few clinical consequences (efficacy/safety).
It is wrong to translate this information by a difference in the effectiveness of - 20% to + 25% between original drugs and generic drugs. As proof, a retrospective analysis of the Food and Drug Administration (FDA) found, in a retrospective analysis including 2,070 studies of bioequivalence submitted between 1996 and 2007 in generic drug dossiers, that the difference in AUC and Cmax between generic drug and originator drug was on average less than 5%.
Is it true that generics have the right to a tolerance of plus or minus 20% of the molecule of the original drug?
It is wrong to translate this information into a difference in bioavailability and, therefore, in efficacy, or the amount of active ingredient from -20% to + 25% between the original drug and the generic drug.
For proof, a retrospective analysis of the Food and Drug Administration (FDA), including 2,070 studies of bioequivalence submitted between 1996 and 2007 in generic drug dossiers, found the difference in AUC and Cmax between the generic drug and brand-name drug was on average less than 5%.
The values + or - 20% or 25% come from the demonstration of the bioequivalence when the confidence interval [CI90] of the ratio (generic drug/originator drug) of the means of the areas under the curve (AUC) and of the maximum blood concentrations (Cmax) is entirely between 80 and 125%.
This interval [80% - 125%] has been defined internationally by considering that a variation of the ratio of means up to 20% has only a few clinical consequences (efficacy/safety).