Much Ado About Nothing - How to Complicate the Explanation

The Brazilian Pharmaceutical Regulatory Agency - ANVISA is preparing the issuance of a new Resolution that will allow drugs known as “similar” to be interchangeable with reference drugs (originals) and/or generics. The present regulations only allow pharmacies to interchange reference drugs and generics. ANVISA and the Ministry of Health have made a lot of noise in the media about the publication of a Public Consultation (CP) which submits the suggested wording for this new Resolution to stakeholders that may present suggestions to the proposed wording presented by ANVISA. Necessary explanation: with the enactment of Law 9.787/99 that amended Law 6.360/76, Generics (drugs that are bioequivalent with reference drugs and interchangeable between them) were introduced into the market. As a consequence, ANVISA published a Resolution (that had to be corrected three times) to regulate the sales of the generic drugs. The Resolution authorized the pharmacist to substitute the drug prescribed by their respective generics (or vice-versa) unless such substitution had been prohibited by the doctor in the respective prescription. Besides, it was necessary to regulate some very peculiar practices in the Brazilian pharmaceutical market, especially the product known as “similar”. As, until 1999 real generics did not exist in the Brazilian market, among other reasons, for the prohibition to patent pharmaceuticals, the market was supplied, basically, with two types of drugs: originals (reference), that had to submit a vast number of documents and references, including results of clinical studies, to be registered and the “similar drugs” that did not need to submit clinical studies or bioequivalence studies or even therapeutic equivalence documents. So “similar” drugs had no need to show that they had the same efficacy and/or safety of the original drugs they copied. To correct this “flaw” in the legislation and, considering that drug registrations must be renewed every five years, ANVISA published a Resolution in May of 2003 (RDC 134/2003) which required that all “similar” drugs registered should demonstrate their efficacy and safety, as follows: (a) On the first renewal after the publishing of the Resolution, present studies demonstrating pharmaceutical equivalence studies in relation to the reference drug. (b) On the second renewal after the publishing of the Resolution present studies demonstrating the bioequivalence in relation to the reference drug. As a result, by the end of the first semester of 2014, when the new Resolution under study will probably be published, more than ten years will have elapsed since the publication of RDC 134/03. So, all similar drugs will already have complied with the requirements above or they will have had their registrations cancelled by ANVISA. In summary, under the legislation in force there are, in the Brazilian Market today, the following types of drugs:  Reference Drugs (Originals);  Generic Drugs (bioequivalent to the reference drugs) and  Similar Drugs (also bioequivalent to the reference drugs) In this scenario, similar drugs could also be called Branded Generics and will be as interchangeable as the generic drugs, as per the legal definition of “interchangeable drugs because article 3 item XXIII of Law 6.360/76 defines “Interchangeable Pharmaceutical Product as a “therapeutic equivalent of a reference drug” and consequently interchangeable drugs are all bioequivalent drugs. Considering that all drugs existing in the market are (or will be by mid 2014) either reference drugs or their bioequivalent (branded or not) the new Resolution, at least in what it relates to the interchangeability, seems to be absolutely unnecessary. It appears that the expenses in human resources and other activities related to the preparation and discussion of the proposed new Resolution could have been avoided if ANVISA had made a more technical analysis of the scenario and of the existing legislation and regulation. This situation could be explained, but not accepted as: (1) resulting from the Brazilian Notarial Culture which concedes that ancillary regulations may be more enforceable than the legislation it regulates and, (2) as an instrument of propaganda that sells as a huge benefit for the population a “new” idea that, in fact simply resulted from procedural corrective measures taken more than ten years ago. It is worth noticing, also, some aspects of the proposed Resolution that are, at least confusing. In spite of the legal requirement that similar drugs prove bioequivalence to the respective reference drug, there is a technical mistake in article 2 of the proposed Resolution that says: "the similar drug, which studies related to pharmaceutical equivalence, relative bio availability / bioequivalence and exception have been presented o ANVISA, and approved, shall be considered interchangeable.” The above wording allows the interpretation that it would be possible to maintain in the Brazilian market, similar drugs that have not demonstrated to be bioequivalent to their respective reference drugs, which would only be possible under complete violation of the sole paragraph of article 8 of Resolution RDC 134/03. Another very relevant and confusing part of the proposed Resolution refers to the packaging material for these “now” interchangeable similar drugs. As per the proposal the packaging would change and have to show a LOGO that identifies the drug as “interchangeable. So, as all similar drugs would be technically interchangeable (as they would have demonstrated bioequivalence) the market would have interchangeable generic drugs, and interchangeable similar drugs, each with a different packaging with different apparent information, the consumers are bound to get very confused. Besides there will be significant costs to the industry in adapting their respective packaging keeping in mind that this is a market under strict price control. Last but not least, there may BA some confusion generated from the pricing regulations as article 10 of the proposed Resolution sets forth that this “new” interchangeable similar drugs must have new market prices determined by the Drug Pricing Authority (CMED) before they can be sold. The pricing regulation as in force today determines different prices for generic drugs and for similar drugs. The first cannot have prices that are higher than 65% of the price of the reference drug and the latter will have a price not higher than the average of other similar drugs with the same active ingredient and presentation (Resolutions CMED 02/2004 and 04/2005). The fact that similar drugs will now be considered (by yet another legal definition) what they already are, that is, interchangeable, does not seem to be reason enough to justify any change in the pricing regulation as it is written today. The only reasonable change in this pricing regulation would be its total revocation as it only serves to create distortions in the market by creating a kind of “regulated cartel”. The regulation, as shown below, fosters the creation of an artificial price that may never be practiced but that is kept as some sort of safeguard in case price readjustments, granted by the pricing authority are not reasonable. Visiting a couple of pharmacies close to my Office I have found the following prices for drugs (same presentation and concentration): Generic Name: Omeprazol Price of Generic Drug: R$ 106,00 Price of Similar Drug: R$ 33,00 Generic Name: Sinvastatin Price of Generic Drug: R$ 62,00 Price of Similar Drug: R$ 39,00 What can be expected of the new regulation that will determine the new pricing for the “now” interchangeable similar drugs? Anyway, what is the reason for this new Resolution on “now” interchangeable similar drugs? Just to create a political moment that may generate dividends? Wouldn’t it be simpler, more economic sound and effective that health authorities simply implement a widespread public campaign informing the population that similar drugs are also bioequivalent? One more it becomes evident that simplicity and practicality are not the focus of the Brazilian public administration and that nothing is more important that generating some apparent “new” benefit for the population. Mais uma vez fica demonstrado que a simplicidade e praticidade passam longe da administração pública no Brasil e que nada é mais importante do que gerar um aparente benefício para a população. Marcos Lobo de Freitas Levy is a lawyer specializing in life sciences regulatory at A. Lopes Muniz Advogados Associados. Silvia V. Fridman is a pharmacist and a consultant in pharmaceutical regulatory.