Faq:
Why does an equivalent medicine cost less than a branded medicine?
The equivalent medicine reimbursed by the SSN must by law be offered at a price which is at least 20% lower than that of the original medicine. This low price is possible because of the lower costs the pharmaceutical companies have to bear for the research and development of equivalent medicines.
Indeed, once the bioequivalence of the equivalent medicine to the original medicine has been shown, it is not necessary to demonstrate that its therapeutic efficacy is equal to that of the original medicine.
Who saves with equivalent medicines?
When a medicine is reimbursed by the SSN (class A), SSN covers the full costs of the equivalent medicine. In this case the State saves, but the public also saves as there is no difference in price to pay. When the medicine is not reimbursed by the SSN (class C) the equivalent medicine is offered at a lower price compared to the branded medicine. In this case the public saves as the equivalent product costs less than the original one.
Could taking a medicine whose patent protection has lapsed, and which is, therefore, older, mean accepting an outdated therapy?
No, this is not the case. On the contrary, equivalent medicines offer proven therapeutic effects, since we are dealing with compounds that are already widely used in a large number of patients. A lapsed patent implies that the medicine in question has been on the market for at least 10 years, and equivalent medicines are chosen on the basis of widescale use.
The side effects of equivalent medicines are, therefore, well known and are the same as those seen with the original medicine during its long period of protection.
How much can the content in active ingredient vary in an equivalent medicine?
The variability margin is the same for both equivalent medicines and the original medicine. In any medicine, whether it is innovative or an equivalent, variability in the active ingredient content is allowed, usually (in EC guidelines) within the range of 95% to 105% of the theoretic value. In other words, a medicine, whether original or equivalent, is considered acceptable if the active ingredient content does not differ by more than 5% from the value indicated on the label.
How much can the effectiveness of an equivalent medicine vary compared to the original medicine? And compared to an equivalent medicine produced by another pharmaceutical company?
In determining the bioequivalence of two different formulations of the same medicine, you need to bear in mind not only the 95-105% variability in active ingredient (see previous answer), but also the individual variability of the patients who take the medicine. Due to this variability, an identical medicine administered to two different subjects will not produce identical blood levels of the active ingredient (blood or plasma levels) in both subjects, as the rate and extent of absorption, distribution, metabolism and elimination of the active ingredient in the two subjects will be different. Even the same subject who takes the same medicine at different times will not show a perfect correlation in blood levels of the medicine in these two circumstances, because absorption, distribution, metabolism and elimination change throughout the day (circadian rhythm) and throughout life. To take account of this "intra" and "inter" individual variability, the European regulatory authorities have established that a formulation can be considered bioequivalent to another if the average response differs by not more ± 20% of the average response of the reference formulation.
Consequently the acceptable limits for fluctuations in the values of the parameters used for evaluating bioequivalence are ± 20%. It should be noted that this does not mean a difference of ± 20% in the efficacy between the two medicines, but only that it is possible to see a difference in the effects produced by the medicine in the sample of individuals who take part in the bioequivalence study, due to the variability in the reference parameters relating to those individuals. When an appropriate medicine for a patient has been identified, along with its correct dosage to produce a certain therapeutic effect, such effect will be maintained if an equivalent medicine is used in place of the original medicine.
How do the excipients influence the efficacy of an equivalent medicine?
The excipients are "neutral" (pharmacologically inactive) ingredients of a medicine. They are added for various reasons: to render the prescribed medicine easier to use at very low doses, to dissolve the active ingredient when the medicine is to be injected, to improve the flavour of the medicine for oral use and so on. Some excipients may interfere with the absorption phase of the medicine, slowing it down (fatty substances or polymers), accelerating it (cyclodextrine or salification of the active ingredient), inhibiting it in the stomach and allowing it only in the intestine (gastro-resistant polymers). These means are used in formulations to modify the absorption rate and therefore, to some degree, the duration of action of a medicine. Equivalent medicines do not necessarily need to contain the same excipients as the original medicine. What must be guaranteed is that the release profile of the active ingredient from the equivalent medicine is the same as the one from the original medicine. This is guaranteed by the demonstration of bioequivalence.
Independently of excipient composition, if the active ingredient is released at the same speed and in the same quantity by both the original medicine and equivalent medicine (i.e. the two medicines are bioequivalent) the therapeutic action will also be the same.
There are some excipients, however, both in the original medicine and in the respective equivalent medicine, which require caution when used by certain groups of patients. The presence of these excipients in every medicine, independently of whether it is an original medicine or equivalent medicine, is indicated in the package leaflet with an appropriate warning. A list of these excipients has been drawn up by the EU commission and can be obtained from the web site of the European Medicines Agency, to which you should refer for more detailed information
(http://www.emea.europa.eu/pdfs/human/productinfo/3bc7a_200307en.pdf)
Could the presence of starch as an excipient be a problem for patients suffering from celiac disease?
The European guidelines state that any type of starch, including that derived from wheat, can be taken by patients suffering from celiac disease without any risk. In fact, the starch used as excipient is the pharmaceutical variety, which contains only traces of gluten, as required by the pharmacopoeia. Any medicine, therefore, whether original or equivalent, can be taken without any risk by celiac disease patients even when it contains starch - based excipients.
Why do the therapeutic indications, contraindications or other paragraphs in the package leaflet of the equivalent medicine sometimes differ from those of the originator medicine?
The package leaflet of the original medicine can differ from that of the equivalent medicine. This happens when the equivalent medicine is authorised through a European procedure. In this case the package leaflet that is approved at the end of the procedure and is the same in all the EU countries, represents a synthesis of all the leaflets approved for the originator in the countries concerned. Since the package leaflets of many medicines are not harmonised among different countries, there may be some differences in the final version of the text approved for the equivalent medicine, which is, usually, more restrictive. In most cases the package leaflet approved for the equivalent medicine is more up to date, because it summarises the collective experience of the medicine in different countries and throughout the period in which it has been on the market.
The European Union has plans to harmonise the package leaflets within its territory to rectify these differences in the long-term. For the time being the inclusion in the AIFA (Agenzia Italiana del Farmaco) Transparency List is the best indicator of substitutability. This AIFA list certifies bioequivalence and, consequently, legitimacy. On the contrary, any differences in the warnings relating to excipients, which can vary between the equivalent medicine and the original one, are important.
Why do equivalent medicines sometimes have a shorter shelf-life (i.e. their expiry date is earlier) than original medicines?
A medicine's shelf life is established on the basis of the data presented by the producer, up to a maximum, by law, of 5 years. Original medicines have been on the market longer, and have usually collected data over a longer period of time, which have enabled the originator to obtain a longer shelf life compared to a corresponding equivalent. Later on, however, an equivalent medicine often obtains, after presenting supplementary data, an extension to its shelf life.
A shorter shelf life is not, therefore, due to lower stability in the equivalent compared to the original medicine, but only to the fact that data for the equivalent is not yet available for a long enough period. In any case, it should be borne in mind that an equivalent medicine, just like the original one, can be used in absolute safety right up to the last day of the month indicated as the expiry date.
