An equivalent medicine is a medicine that contains the same quantity of active ingredient and has the same bioavailability as a branded medicine with an expired patent.
The protection offered by a patent allows a company, which has carried the costs of research, development and launch of a new product, to maintain its monopoly in the sale of this product for several years. At the end of this period of protection provided by the patent, a medicine may then be produced by other pharmaceutical companies and offered on the market at a lower price.
GENERICS BECOME EQUIVALENT MEDICINES
The definition of an equivalent medicine is contained in Article 10, subsection 5, Letter b of the Legislative Decree 219 of 2006, which states: "generic medicinal product: a medicinal product having the same qualitative and quantitative composition in terms of active ingredient and the same pharmaceutical form of a reference medicinal product and which bioequivalence to the reference medicinal product has been demonstrated by appropriate studies".
WHAT THE LAW SAYS
La definizione della nozione di farmaco generico è contenuta nell'Articolo 10 Comma 5 Lettera b del Decreto Legislativo 219 del 2006, che così recita in proposito: "medicinale generico: un medicinale che ha la stessa composizione qualitativa e quantitativa di sostanze attive e la stessa forma farmaceutica del medicinale di riferimento nonché una bioequivalenza con il medicinale di riferimento dimostrata da studi appropriati di biodisponibilità".
THE CONCEPT OF BIOEQUIVALENCE
Two medicinal products are defined as bioequivalent when their bioavailability, i.e. the quantity of active ingredient that is released into the bloodstream, and the rate at which it is released are equivalent.
In practice, the concept of equivalent medicine is based on the assumption that, in the same subject, equal active substance plasma concentrations over time will produce an equal concentration of the substance at the site of action and, therefore, an equal therapeutic effect.
This is why the Agenzia Italiana del Farmaco (AIFA - Italian Medicines Agency) grants authorisation to produce and market an equivalent medicine on condition that the quality of the product is documented and that its bioequivalence to the original medicine is demonstrated.
WHY IT COST LESS
An equivalent medicine costs less in comparison to the original because the costs of research have been recovered during the period in which the product was under patent.
It is well known that to demonstrate the efficacy and safety of a new medicine it is necessary to test the product on hundreds or even thousands of subjects. Such testing takes months and has high costs.
On the contrary, a company that produces and markets an equivalent medicine does not have to prove its therapeutic efficacy: if its active ingredient reaches the same blood levels as those obtained with the original medicine (i.e. if it is bioequivalent) it therefore has the same therapeutic efficacy. Demonstrating bioequivalence to a medicine that is known to be safe and effective requires much less time and greatly reduced costs, and so the equivalent medicine can be marketed at lower price.
THE ROLE OF THE DOCTOR
Generic drugs have been available in Italy for more than ten years now and the General Practitioner (GP) has learned how to use them better.
Nevertheless, in the everyday clinical practice, some critical points still appear that directly involve the peculiar relationship between the GP and the patient: the GP is the cornerstone of the healing process and the patient has trust in this relationship.
The widespread availability of drugs based on the same active ingredient and for which patent protection has expired may generate confusion: the prescription of a generic drug, though already accepted as far as efficacy and safety are concerned, needs to be supported by specific information to patients who, in the general medicine setting, are often elderly and fragile and who may have memorized some peculiar element of branded drugs (such as commercial name, packaging, color of the tablets etc.).
In the prescribing choice, the GP needs to manage the possible objections not only arising from the patient but also from other health professionals such as the Specialist (it may for instance happen that the patient is recommended to take a branded medicinal product at hospital discharge) and the Pharmacist, who can substitute the generic product prescribed by the GP with a different one.
The GP has a mean to grant both the therapeutic choice and the patient: add to the prescription the ban to substitute in all cases where this is considered appropriate, avoiding therefore the chance of repeated substitutions among different generic products, potentially confounding for the patient.
Furthermore, the note "not-substitutable" allows the GP to evaluate the results of the therapy, i.e. check in time whether a specific product generates the expected benefit for the patient, which is an essential factor for drugs intended to heal chronic illnesses, where efficacy needs to be verified in time.
The term active ingredient indicates the substance that possesses therapeutic activity in a medicine.
The remaining components of a pharmaceutical form are called excipients and are utilised to improve its stability, storage and administration or to modify the release rate of the active ingredient.
The bioavailability of a medicine measures the quantity of the medicine that is absorbed and made available to exert therapeutic effects on the body.
A medicine administered intravenously will have a bioavailability equal to 100%, as, entering directly into the bloodstream, it will be immediately available to organs and tissues, while medicines administered using other routes (e.g: orally) will have a lower bioavailability value because of partial absorption.
Originator or Original Medicine
An original medicine or reference medicine is a medicine that has a marketing authorization granted on the basis of a complete dossier, containing comprehensive data relating to its chemical quality, the results of toxicology and pharmacology studies (in laboratory animals) and the results of the clinical trial program (studies in patients). An authorised medicine is sold exclusively by the company that developed it, for the length of its protection under patent.
A generic or equivalent medicine is a medicine that has the same active ingredient, the same strength and the same pharmaceutical form as the original medicine, but is authorised after the protection afforded by the patent has lapsed, subject to documentation of its chemical quality and demonstration of bioequivalence to the original medicine. As the medicine is bioequivalent, reference may be made to the clinical and toxicological-pharmacological tests carried out by the originator.
Patent and patent protection
The patent assures the holder that for the duration of the patent, the patentee has exclusive industrial property rights - and, consequently, utilisation and exploitation rights - related to the patented product and constitutes, therefore, a sort of temporary right of monopoly in favour of the said patent holder. The granting of such exclusive rights is directed at remunerating the costs and investments relating to the ideation and development of the patented product by the patentee and acts, therefore, as an incentive for research.
The regulations for patenting pharmaceutical products in Italy goes back to 1979, the year that decree 338 of the President of the Republic was promulgated.
In the case of medicines, the necessity to demonstrate efficacy and safety with lengthy clinical tests, means that years elapse between the achievement of a patent and of a marketing authorisation. For this reason the legislation provide a further layer of protection that compensate the patentee, at least partly, for the delay in the economic exploitation of the invention.
This further protection is known as CPC (Certificato Complementare di Protezione - or - Complementary Protection Certificate)
After one or more equivalent medicines of a medicine reimbursed by the SSN, whose patent protection has lapsed, have been authorized, AIFA includes both the original medicine and its equivalents in a list, which is up-dated monthly, called the "transparency list".
It is available on the AIFA web site, http://www.agenziafarmaco.gov.it/it/content/liste-di-trasparenza-e-rimborsabilita
In this list the original medicine and its equivalents are listed together, with their corresponding reference price.
The medicines grouped together on the transparency list can be substituted. This list therefore attests the fact that the listed medicines are considered equivalent and sanctions their substitution.
AT THE PHARMACY: THE OPTION OF SUBSTITUTION
The concept of substitution is closely connected to that of bioequivalence; if a medicinal product is bioequivalent to a reference medicinal product the patient can obtain the latter without paying the price difference.
Substitution is currently regulated by law 221 of 17.12.2012, published on the Official Journal n. 294 of 18.12.2012 ("Development Decree"), which states that the Medical Doctor who visits a patient for the first time and for a chronic illness or for a new episode of a non-chronic illness where several equivalent medicinal products are available, should indicate on the National Health Insurance prescription the name of the active ingredient alone or the name of a specific medicinal product containing that active ingredient, together with the name of the active ingredient. The name of a specific product is binding for the Pharmacist unless substitution is specifically ruled out by the Doctor, with a short justification. The name of the specific medicinal product is also binding for the Pharmacist when said medicinal product is sold at the reimbursed price, unless the patient requires substitution.
In summary: the Medical Doctor should not prescribe the brand name when filling the "red" (reimbursed) prescription for a medicinal product not intended for chronic use or which is used for the first time, when equivalent products are available. The Pharmacist should supply the brand name only when its substitution has been ruled out on the prescription and justified by the Doctor.
The patient can always ask for a specific medicinal product, either branded or generic. If the price of the product required is higher than the reimbursed one, the patient pays the difference.
When to substitute
When the patent protection for a medicine reimbursed by the SSN expires and one or more equivalent medicines are authorised, the Agenzia Italiana del Farmaco (AIFA) includes both the original medicine and its equivalents in a list, which is up-dated monthly, called the "Transparency List".
In this list the original medicine and its corresponding equivalents are listed together with their reference price. The reference price corresponds to the lowest price on the market for that medicine and is also the price reimbursed by the SSN. If a medicine appears on the Transparency List and the prescribing doctor does not specify on the prescription that the medicine "cannot be substituted", the pharmacist is obliged to offer the patient an equivalent medicine at the reference price. Should a prescribing doctor add the instruction "cannot be substituted" or should the patient not accept the substitution, the difference in price between the reference price and the retail price is borne by the patient.
Substitution of non reimbursed medicines
The concept of substitution was also extended to medicines not reimbursed by the SSN (class C medicines, paid for completely by the patient), including the so-called "medicines available without prescription"(*) and "over the counter" medicines (OTCs), by legislative decree 87/05 converted into law 149/05. The law provides that even in this case the pharmacist must inform the patient of the availability of equivalent medicines that may be purchased at a lower price.
This norm was introduced to further encourage the culture of equivalent medicines in Italy, less widespread than in the rest of Europe, especially as compared to Northern Countries.
(*)An Italian class of medicines similar to OTCs, with the only difference that no publicity to the public is allowed.
THE ROLE OF THE PHARMACIST
The pharmacist has a pivotal role to play in the development and dissemination of the use and culture of equivalent medicines. Since 2001, by law, the pharmacist is obliged to inform the patient of the availability of an equivalent medicine corresponding to the original medicine and to inform the patients about the difference in price and the amount of money they have to pay if they decide to buy the original.
The pharmacist also has the important task of reassuring the patient about the quality of the equivalent medicine, the similarity of its therapeutic activity and of the incidence of its side effects compared to those of the original product.