Italian Medicines Agency Agenzia Italiana del Farmaco

Generic medicinal products

Generic (or equivalent) medicines

Generic (or equivalent) medicinal product means a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

For the purposes of the definition of generic medicinal product, it should be borne in mind that the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance if, on the basis of additional information provided by the applicant, they do not differ significantly in properties with regard to safety and efficacy.

The various immediate-release oral pharmaceutical forms shall be considered to be one and the same pharmaceutical form (Article 10, paragraph 5, letter b), of Legislative Decree No 219/2006).

Generic (or equivalent) medicines

Bioequivalence studies

A medicinal product is bioequivalent to the reference product if bioequivalence studies show that, with the same dose, blood concentration profiles over time overlap and, therefore, such concentrations are unlikely to produce significant differences in efficacy and safety (therapeutic effects/adverse reactions).  

Bioequivalence studies are pharmacokinetic studies (from the Greek kinesis, movement, and pharmakon, medicine) that aim at comparing the bioavailability of two medicinal products, i.e. the amount of medicinal product that passes into the blood circulation after administration, in relation to the speed at which this occurs.

Bioequivalence is assessed by comparing the parameters characterising bioavailability (the maximum plasma concentration of the medicine [Cmax]; the time at which this concentration is reached after administration [Tmax]; the area under the curve [AUC], which represents the trend in the medicine’s plasma concentration over time).

The ratio of the mean concentrations of AUC and Cmax, obtained after administration of the two medicines, statistically analysed, should fall within an acceptability range of 0.80-1.25, with a 90% probability (or within a ± 20% range if the difference between the parameters is used instead of their ratio). The confidence interval (0.80-1.25) has been agreed at international level, taking into account the variations in bioavailability that may occur in one person receiving that specific medicinal product at different times, and in different subjects.

Where bioequivalence between the generic medicinal product and the reference medicinal product is demonstrated, efficacy and safety are considered overlapping and medicinal products are deemed to be therapeutically equivalent.

For generic medicinal products, there is therefore a derogation from the obligation to submit pre-clinical tests (pharmacological and toxicological studies) and clinical trials, as laid down in Article 8, paragraph 3, letter l), of Legislative Decree No 219/2006, since they have already been submitted and assessed by the regulatory authority for the reference medicinal product.

The quality of a generic  medicinal product is comprehensively assessed in accordance with applicable European legislation and guidelines. In addition, equivalence in terms of critical quality attributes between generic and reference medicinal products is assessed, taking into account that suppliers of raw materials, formulation, manufacturing process and manufacturers are usually different and could characterise the quality and stability of medicinal products differently.  

Generic medicines: quality, efficacy and safety

Generic medicines meet the same quality, efficacy and safety standards as the reference medicinal products. A generic medicine may then be prescribed and used in lieu of the reference medicinal product (also known as branded medicine). However, the respective list of excipients reported in the package leaflet needs to be checked in case of subjects with known intolerances.

Generic medicines: market authorisation

The marketing of a generic medicinal product must comply with the rules concerning the protection of industrial and commercial property. It occurs only upon expiry of the reference medicinal product’s patent coverage and supplementary protection certificate, if any, as well as upon expiry of the data exclusivity and market exclusivity rights provided for by EU legislation as a complementary intellectual property protection, in order to enable the reference medicinal product’s marketing authorisation holder to cover the R&D costs incurred.

The data exclusivity right relates to data from pre-clinical and clinical studies conducted for the purposes of obtaining a marketing authorisation (MA) for the reference medicinal product. It provides for its protection over a period of eight years from the date of first authorisation. 

Generic medicines: price

Generic medicinal products have a lower price than the reference medicinal products by at least 20% as a direct consequence of the patent expiry of the reference medicinal product’s active ingredient as well as the expiry of the exclusivity period. The placing on the market of a generic product is of considerable benefit to both the NHS and the citizen, since the savings achieved can be invested in the reimbursement of new innovative medicines for rare or chronic conditions and, given the equal quality, safety and efficacy, the range of patients who can access the medicine is widened.

AIFA’s Transparency List

When generic medicinal products are authorised and are classified as category A (i.e. reimbursed by the National Health Service), they may be included in AIFA’s Transparency List, which is updated monthly.

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