Biosimilars

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Afssaps’ MA (Marketing Authorisation) commission discussed biosimilars on the 12th of May 2011. An information paper was published on 13/05/2011.

A biosimilar (similar biological medicinal product) is a medicinal product which is similar to a reference biological medicinal product that has been already authorized in the European Union. The principle of similarity applies to any biological medicinal product whose patent has expired.

Similar biological medicinal products are evaluated by the European Medicines Agency (EMA).

Biological medicinal product: a product, the active substance of which is a biological substance. A biological substance is a substance that is produced by or extracted from a biological source (cell or living organism or derived from them).

(Commission Directive 2003/63/EC of 25 June 2003)

Biosimilars have to have:

  • similar physicochemical-biological properties,
  • the same active substance,
  • the same pharmaceutical form,

of the reference product. Moreover, efficacy and security must be equivalent to that of the reference medicinal product.

Due to the biological variety of production sources, some differences on the manufacture of biological medicinal products can have an impact on the clinical properties of the final biological product.

Therefore, the MA is delivered on the basis of equivalent therapeutical results, and not only on the basis of bioequivalence as for chemical generic products. And so, the demonstration of similarity needs new pre-clinical and clinical tests.

Reference products are not identical to similar biological products, therefore, the principle of substitution, applied for chemical generic products, cannot be automatically applied for biosimilars.

(Principle for substitution

Products that have:

  • the same active substance in the same amount
  • the same pharmaceutical form
  • an equivalent security and efficacy profile
  • proved to be bioequivalent to a reference biological product of a certain generic group

belong to the same generic group. They can be replaced by another similar biological product of the same generic group. The reference product and its biosimilars belong to the same generic group).

Biosimialrs are, in principle, authorised to treat the same diseases than the reference product. However, they can have less indications than the reference product (due namely to the absence of efficacy and security studies confirming a concerned indication).

To assure pharmacovigilance and the security of patients, Afssaps recommends to limit the use of biosimilars in the same patient.

Since 2006, 14 biosimilars have been authorized in the European Union (corresponding to 4 substances):

Epoetin (alfa and zeta): epoetin is a copy of human hormone erythropoietin, which stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys.

Epoetin is used to treat namely anaemia (reduced number of red blood cells) on patients with renal failure or in certain types of cancer.

The epoetin is produced by a cell that has received a gene, which makes it able to produce it.

Filgrastim: filgrastim is very similar to a human protein called “granulocyte colony stimulating factor” (G-CSF), which stimulates the production of white bood cells by the bone marrow.

Filgrastim is used to stimulate the white blood cells production. It is produced by bacterium that has received a gene, which makes it able to produce it (“recombinant DNA technology”).

Somatropin: somatropin is identical to a growth hormone (GH) secreted by the pituitary gland (a gland located at the base of the brain). This hormone promotes growth during childhood and adolescence, and also acts on the way the body handles proteins, fat and carbohydrates.

Somatropin is made by a bacterium which has received a gene that makes it able to produce it (“recombinant DNA technology”).

More information: Guideline on similar biological medicinal products CHMP/437/04 (30th October 2005).