The European Medicines Agency recommended approval of Omnitrope, which copies an existing growth hormone prescribed for undersized children. If given final OK by the European Commission, Omnitrope could be on the market later this year and would be the first-ever generic biotechnology drug. Omnitrope marks the first real threat to the near monopoly enjoyed by biotechnology drugmakers.
Generic biologics have been a tough fight in the U.S. as biotech drug makers say it would be dangerous to allow approval for biotech drugs since generics don’t have to perform expensive human tests but simply show their molecules are “equivalent” to existing drugs. The argument is that biotechnology drugs are made up of proteins, antibodies, and other substances derived from living cells, which can be extremely difficult, if not impossible, to reproduce exactly.
So far, the FDA has agreed. The Hatch-Waxman Act doesn’t include biologicals and the FDA has never issued any guidelines for getting biogenerics to market more quickly. While a single biotech drug can generate over $1 billon a year in revenues, biotechnology companies are coming under increasing pressure from possible generic competition due to high healthcare costs.
In the European case for Sandoz’ Omnitrope (somatropin), the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending to grant a marketing authorization for Omnitrope for treatment of growth disturbance and growth hormone deficiency. The active substance of Omnitrope is somatropin, a growth hormone produced by recombinant DNA technology. Somatropin is a hormone of importance for growth and for the metabolism of lipids, carbohydrates and proteins.
The Committee for Medicinal Products for Human Use (CHMP) issues specific guidelines concerning the scientific data to be provided to substantiate the claim of similarity used as the basis for a Marketing Authorization Application (MAA) for any biological medicinal product, e.g.: medicinal products containing biotechnology-derived proteins as active substance, immunologicals such as vaccines, blood-derived products, monoclonal antibodies, etc.
In principle, the concept of a “similar biological medicinal product” is applicable to any biological medicinal product. However, in practice, the success of such a development approach will depend on the ability to characterize the product and therefore to demonstrate the similar nature of the concerned products.
Biological medicinal products are usually more difficult to characterize than chemically derived medicinal products. In addition, there is a spectrum of molecular complexity among the various products (recombinant DNA, blood or plasma-derived, immunologicals, gene and cell-therapy, etc.). Moreover, parameters such as the three-dimensional structure, the amount of acido-basic variants or post-translational modifications such as the glycosylation profile can be significantly altered by changes, which may initially be considered to be ‘minor’ in the manufacturing process. Thus, the safety/efficacy profile of these products is highly dependent on the robustness and the monitoring of quality aspects.
Therefore, the standard generic approach (demonstration of bioequivalence with a reference medicinal product by appropriate bioavailability studies) is normally applied to chemically derived medicinal products. Due to the complexity of biological/biotechnology-derived products the generic approach is scientifically not appropriate for these products. The “similar biological medicinal products” approach, based on a comparability exercise, will then have to be followed.
Comparability exercises to demonstrate similarity are more likely to be applied to highly purified products, which can be thoroughly characterized (such as some biotechnology-derived medicinal products).
The ‘similar biological medicinal product’ approach is more difficult to apply to other types of biological medicinal products, which by their nature are more difficult to characterize, such as biological substances arising from extraction from biological sources and/or those for which little clinical and regulatory experience has been gained.
Whether a medicinal product would be acceptable using the ‘similar biological medicinal product’ approach depends on the state of the art of analytical procedures, the manufacturing processes employed, as well as clinical and regulatory experiences. The active substance of a similar biological medicinal product must be similar, in molecular and biological terms, to the active substance of the reference medicinal product.
The pharmaceutical form, strength and route of administration of the similar biological medicinal product should be the same as that of the reference medicinal product. When the pharmaceutical form, the strength or the route of administration is not the same; additional data in the context of the comparability exercise should be provided. Any differences between the similar biological medicinal product and the reference medicinal product will have to be justified by appropriate studies on a case-by-case basis.
CHMP guidelines are available here. (Guidance Documents / Biosimilar Products)
