Barreda Moller writes...

Pharmaceutical patent, generic pharmaceuticals and bioequivalence

The invention patent has a 20-year term, counted from the filing date of the respective application for registration, once it is granted. The patent grants its owner the exclusive right to prevent third parties not having the owner’s consent from performing any of the following acts: a) when a product is claimed in the patent: i) manufacture the product; ii) offer for sale, sale or use the product; or import it for any of these purposes; and, b) when a process is claimed in the patent: i) use the process; or ii) perform any of the acts indicated in a) with respect to a product obtained directly by the process.

Nevertheless, once the invention patent protection term has expired, any person is free to manufacture the product and offer it for sale. In the case of pharmaceutical products, the version which copies exactly the original product which patent has expired is the so-called “generic drug” or “multisource drug”. It is not a free or unrestricted copy. The copy, according to the recommendations of the World Health Organization (WHO), must undergo a bioequivalence test which guarantees consumers its bioavailability, in other words that the amount of the medicament achieves the therapeutic target and that the rate and magnitude of its absorption by the organism be the same, that is, in simple terms, that the medicament ingestion produces the same therapeutic effects as the copied original product.

In an ideal market, the appearance of “generic drugs” should guarantee a reduction in the price of medicines in favor of the consumer and in some countries the “generic drug” is indeed sold at generally lower prices, as occurs in the United States of America, Japan and Europe. The costs of manufacturing the “generic drug” are lower since the development of a new molecule is not required and, therefore, it is not necessary to perform clinical assays, but simply demonstrate its bioequivalence. These lower production costs should inure in a price difference but without lowering the product quality so safety and efficacy should have to be guaranteed in favor of the consumer.

The problem arises in markets in which the rules are not clear and in which distortions which certainly do not benefit consumers occur. After heated debates, our country promulgated in 2009, Act No. 29459 or the Act on Pharmaceutical Products, Medical Devices and Health Products to give a balanced solution to the matter. Article 10 of said Act establishes, according to what is recommended by the WHO, that bioequivalence studies (interchangeability) in vivo be demandable to the products of high health risk, considering the exceptions according to the biopharmaceutical classification in compliance with the graduality principle. This will allow guaranteeing the efficacy, safety and quality of the medicaments commercialized in the country. In this regard, to conduct the studies of therapeutic equivalence, either through comparative studies in vivo or through studies in vitro, as well as to exclude from these studies certain products, it is essential to define and standardize the conditions and requirements that the studies must meet to demonstrate therapeutic equivalence and, therefore, the interchangeability.

For this purpose, the General Bureau for Medicines, Inputs and Drugs (Dirección General de Medicamentos, Insumos y Drogas -DIGEMID) of the Health Ministry was in charge of preparing, with the participation of the National Center of Quality Control (Centro Nacional de Control de Calidad -CNCC) of the Health National Institute (Instituto Nacional de Salud -INS), the proposal of health policy which rules the studies to establish the therapeutic equivalence of medicines, a proposal which also counted on the contributions and suggestions of diverse public and private institutions. Nevertheless, up to date this policy is not approved due to the difficulty in finding a break-even point between the economic interests of the laboratories which own the original products and the national laboratories which copy the original product to produce the generic drug. The first demand that every generic or multifunctional drug conducts the interchangeability or bioequivalence tests whereas the second demand that said test only limits to those products of high health risk (narrow therapeutic window) since those tests would increase the price of the medicines as they would be obliged to assume the cost of the interchangeability or bioequivalence tests which would finally be transferred to the price of the generic drug sold to the consumer.

Anyway, nothing justifies that a generic drug enters the market without having complied with the equivalence tests that guarantee the consumer that the product will have the same therapeutic effect as the copied original since the population health is at risk. Either a generic drug or a multifunctional drug, it must comply the minimum quality standards which guarantee that the product will serve just like its original. In order to mitigate the impact that this could have in the consumer, DIGEMID has proposed that the obligation of having the interchangeability or bioequivalence tests be progressively required, both for the new pharmaceutical products entering the market and for those already existing therein.

This gradual process would start to be applied first for those medicaments of Narrow Therapeutic Index (NTI), that is, those in which, small variations of the levels of concentration administered to the patient can cause serious therapeutic failures (subtherapeutic concentrations) or serious adverse reactions (supratherapeutic concentrations), thus generating important variations in the clinical results. Therefore, the administration of the medicament requires the constant monitoring of the patent, either clinical or pharmacokinetic. But naturally, the idea is that all medicaments finally comply with the equivalence tests in the interests of all consumers.

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