French law disallows 'generic' biosimilars

The community code relating to medicinal products for human use (European Directive 2004/27/EC) has been transposed into French law, and will be published before the beginning of March this year.

The legislation, which has been supported by the European biopharmaceutical industry, takes a cautionary stance in regard to the prickly debate regarding whether so-called biosimilar drugs can really be considered generics in the same way as chemical compounds can be.

The new law to be introduced in France establishes a legal definition of "biosimilar" medicines that notes the potential variability of the active substance and differences in the manufacturing process that prevent the classification of biosimilars as strictly generic products.

Under the new rules, regulatory approval of biosimilars will require additional pre-clinical and clinical data.

Biological medicines are produced using a living system or organism, and their constituent molecules tend to be much larger and more complex than the relatively simple molecular structure of chemically synthesised traditional medicines.

Biosimilar medicines are intended to have the same mechanism of action as the original biological medicine and treat the same disease.

However, there has been considerable debate surrounding the labelling of these biosimilars as generics, as the complex nature of the manufacturing process and the molecules themselves means that it cannot be guaranteed that they are absolutely identical to the original product.

"Analytical and preclinical tests are not sufficient to demonstrate the sameness of two biological products or that they are identical," says the European Association for Bioindustries.

In addition, due to the fact that biosimilar medicines are not completely identical to the biotech reference products, the new French legislation also forbids the automatic substitution of one biological medicine for another at the pharmacy level without the express consent of the prescribing physician.

"A major concern when using biotech medicines is patient safety and drug efficacy," said Dr Carlo Incerti, president of European Biopharmaceutical Enterprises.

"Because biosimilars are not exact copies of the reference products, they cannot have the exact same safety profile as the original biotech medicine."

For example, last year Swiss pharmaceutical company BioPartners was granted approval for Valtropin, a biosimilar version of the human growth hormone somatropin.

The product, however, has slightly different precautions and warnings to the reference product, Eli Lilly's Humatrope (somatropin), and is also produced using yeast as opposed to E.Coli which could lead to clinical complications in some patients.

In a climate of ever-increasing pressure to cut costs and seek out cheaper alternatives to expensive drug treatments, there have been calls to approve biosimilar products which can be cheaper than the original innovator products.

According to the European Generic Medicines Association, the first full wave of biosimilar medicines (only six products – somatropin, interferon alpha, interferon beta, insulin, erythropoietin, and granulocyte-colony stimulating factor) will generate savings of around €2bn-€3bn a year.

However, due to underlying concerns regarding the possibility of adverse immunogenic responses in patients treated with biological products, pharmaceutical legislation regarding biologicals and biosimilars has taken a precautionary approach in an attempt to safeguard against possible unforeseen reactions.

The EU Directive was published back in 2004 with the deadline for countries to transpose it into law by November 2005.

France is trailing behind, with around three quarters of member states having already complied with the directive.

By finally implementing the new law, France will be brought in line with European requirements governing the definition of generic and biosimilar medicines, as well as requirements concerning the granting of marketing authorisations including data protection, and the labelling and packaging of medicines.