Lead Author: Felix Lobo
Organizations: Universidad Carlos III de Madrid
SECOND PROPOSAL FOR EXPANDING THE GENERIC MEDICINAL PRODUCT MARKETS, AFFORDABLE PRICES AND ACCESS TO THE MEDICINAL PRODUCTS FOR THE DISADVANTAGED, THROUGH APPROPRIATE NATIONAL AND INTERNATIONAL REGULATION.
PROPOSAL 2. ATTRIBUTE ONE SINGLE INN TO BIOLOGICAL MEDICINAL PRODUCTS, WITH NO ADDITIONAL PORTIONS OR QUALIFIERS, AND IDENTIFY THE MANUFACTURER AND THE MANUFACTURING PROCESS THROUGH THE NAME OR A BRAND NAME
Establishing the equivalence between innovative biological medicinal products with expired patents and products with the same active ingredient launched on the market to compete with lower prices has some specific problems:
• It deals with proteins, large and complex molecules, different from chemically synthesized medicinal products.
• Its production methods are complex, more subject to variations than chemically synthesized medicinal products.
• They could be immunogenic
• Many are applied parenterally
Products with the same composition manufactured and sold once the original patent expires have come to be known as biosimilar products.
The biological medicinal products and their biosimilar products currently are at the core of the majority of medicinal product innovation and they are of great economic importance.
European Union regulations on this matter have advanced. Their main points are:
• Directive 2003/63/EC establishes the concept of “biologically similar medicinal product”, “biosimilar medicinal product”: “Biological medicinal product that has been developed as the equivalent to another biological medicinal product already sold (called "reference medicinal product").
• The active ingredient is essentially the same
• There may be small differences due to the complexity of the structure and the production method.
• When a biosimilar medicinal product is authorized it is because these differences have no significant impact on safety or efficacy.
But the most important mandate to ensure the equivalence is established by Directive 2004/27/EC, which amends Art. 10 of Directive 2001/83/EC:
“When a biological medicinal product that I similar to a reference biological product does not meet the conditions for defining generic medicinal products, due in particular to differences in raw materials or differences in the manufacturing process for the biological medicinal product and the reference biological product, the results from the appropriate preclinical or clinical trials concerning these conditions shall be provided.”
Currently it is a matter of the highest importance to ensure, as European legislation does, that the biosimilar products are equivalent to the originals, and, therefore, interchangeable without the intervention of the physician, through substitution by the pharmacist or directly through the health system when selecting them. If the response is positive, the field for price competition is much larger than if it is negative. It is a technical issue. The funders and the companies selling biosimilar products are well-disposed to the positive responses while the companies owning reference biological products and well-disposed to negative ones. If the biosimilar products can be considered equivalent to the innovators they could follow the path of the chemically-synthesized genetics and, once the patent expires, there will be more markets for biosimilar products dominated by price competition and affordable price levels.
2. BIOLOGICAL PRODUCTS AND INNs
The WHO group of INN experts, when choosing the names for the recombinant proteins, do not address substances with well-defined structures, but products with a highly complex composition or even mixtures of those products.
There is a clear conflict of interest:
• The innovative biological product companies have an interest in having an INN attributed exclusively to their product. If an INN is attributed exclusively to a reference biological medicinal product and subsequent biosimilarproducts are designated with a different INN, the innovating company owning the former would have a potential monopoly that would extend beyond expiration of the patent. The nomenclature would be the strongest way to differentiate between a reference product and successive biosimilar products and among the latters, drastically reducing the options for the competition in terms of price.
• The companies marketing biosimilar products have a mutual interest in having the INN be the same as that for the reference product.
• The consumers do as well if they are therapeutically equivalent
The current situation can be summarized as follows:
• Currently 40% of INN applications refer to biological substances.
• INNs for biosimilar products follow the general principles.
• But some companies have already established a special system to characterize the biosimilar products (United States, Japan, Australia). For example, non-glycosylated protein biosimilar products have the same INN, while the glycosylated proteinshave a different name from the reference product), (one Greek letter added).
These special systems could undermine the integrity of the INN system, which could be a negative from the public health perspective and decrease the economic advantages of the price competition that could occur with the biosimilar products.
Various proposals are being used to handle these problems. Some tend to introduce additional items or "biological qualifiers."
• A characteristic element or unique special code added to the common name (Biological Qualifier, to indicate that it is a biosimilar product and which one it is
• A sequence of letters following the start of the INN?
• The code would be attributed to the substance but not the product, despite the fact that the product is what is being authorized and sold.
The European Medicines Agency has considered this code necessary, since in the European Union they trust that biosimilar products have a good level of equivalence with the reference products. (MEGERLIN… HA 2013).
3. A PROPOSED SOLUTION FOR THE PROBLEM OF INNs FOR BIOLOGICAL PRODUCTS
It is of the greatest importance to ,maintain the integrity of the INN system. This requires preserving its universality, such that the nonproprietary names are truly global or international s has happened to date. On the other hand, from the economic point of view it is necessary to prevent having international names with qualifier s be appropriated by a specific manufacturer or owner. This would give a permanent, universal advantage on the market, with the most effective differentiation. This advantage would result in less price competition and higher price levels in all of the countries for biological products.
Our proposal has two facets, one negative and the other positive:
• There will be no biological variants or qualifiers in the INN system. There will be only one for each substance.
• To address the problem of possible variations derived from the different manufacturing procedures, the notational legislations should make it obligatory that on transactions involving these products, and above all on prescriptions from the doctors, there must be the INN plus the manufacturer name or one of its trademarks. This will solve the problem without undermining the INN system and with no detriment to price competition.
Bibliography and References
LOBO, F.: Políticas actuales de precios de medicamentos en Europa: panorama general. Springer Healthcare, Madrid 2015. 181 p. ISBN 978-84-940-3469-5
LOBO, F.: La intervención de precios de los medicamentos en España. Panorama de la regulación y los estudios empíricos, Springer Healthcare, Madrid 2013. 159 p. ISBN 978-84-940-3468-8.
FELDMAN, R. y LOBO, F.: “Competition in prescription drug markets: the roles of trademarks, advertising, and generic names”, The European Journal of Health Economics, 14(4): 667-675, August 2013. ISSN 1618-7598; e-ISSN 1618-7601. DOI 10.1007/s10198-012-0414-7.
LOBO, F. y FELDMAN, R.: ”Generic Drug Names and Social Welfare”, Journal of Health Politics, Policy and Law, 38(3): 573-597, Junio 2013. ISSN: 0361-6878; e-ISSN: 1527-1927. DOI 10.1215/03616878-2079505.