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The use of medication is undeniably crucial for extending our lives with the highest possible quality, aligning with advancements in science. As a result, medication leaflets are familiar to everyone, whether or not they are involved in the pharmaceutical sector. However, the same level of familiarity does not extend to the concepts of generic medicines and patented drugs.

Medications with active patents are innovative products (also known as reference products or medicines), for which the applicant, which is more often than not the manufacturer, has obtained temporary ownership rights (patent) from the Brazilian Patent and Trademark Office (BRPTO), in Brazil. This title grants the applicant exclusive rights to develop and commercialize their invention for a period of 20 years, starting from the date of the initial application filing with the BRPTO, as recommended by Law #9,279/76.

Generic medicines in Brazil are governed by Law #9,787/99. By definition, these medications are similar to a reference or innovative product and are intended to be interchangeable therewith. They are typically produced after the expiration of patent protection or other exclusivity rights, once their effectiveness, safety, and quality have been proven. Following this, they are designated by the Common Brazilian Denomination (the approved name of the drug or its pharmacologically active ingredient by the federal health surveillance agency) or, if not available, by the international common name (the name recommended by the World Health Organization).

Additionally, Brazil permits the marketing of similar medicines, under regulation of Anvisa (the Brazilian Food and Drug Agency). These deviate from generic medicines in that they bear a brand, whereas generic medicines are prohibited from using brands and may only be identified by the Common Brazilian Denomination, i.e., its active ingredient. The commonality between generic and similar medicines is that both may only be marketed when there is no longer patent protection for the innovative or reference medicine.

It is essential to note that while the BRPTO is responsible for registering patents, trademarks, and industrial designs in Brazil, Anvisa is the specialized agency responsible for registering and overseeing the commercialization of these medicines, whether they are patented, generic, or similar. Importantly, the BRPTO has never intervened in Anvisa's actions regarding the approval or rejection of medicine registrations. Conversely, Anvisa has historically intervened in BRPTO's actions regarding the granting or rejection of a patent, pursuant to Article 229-C of Law 9,279/76, through a process formerly known as prior approval. However, Law 14,195/01 repealed this provision, with the goal of expediting the evaluation of more than 1000 medicine patent applications, which had, at the time, created a backlog.

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1.1. THE role of medication leaflets

Medication leaflets, as established by the Ministry of Health, are a sanitary legal document which provides guidance on how to use medications. Furthermore, it is an essential guidance tool for patients and healthcare professionals, as it must contain information on:

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ELEMENTS OF A MEDICATION LEAFLET

1. Prescription

2. Preparation

3. Administration

4. Warning

5. Guidelines for Safe Use and Effective Treatment

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Medication leaflets are provided for in Law #6,360/76, which establishes regulatory standards for the pharmaceutical sector. However, the specific regulations governing these leaflets are outlined in Anvisa's RDC Rule #47/2009, which provides all technical and regulatory requirements for the creation of medication leaflets.

Moreover, the concept of medication leaflets has evolved to accommodate individuals with visual impairments, with special leaflets available (i) in audio or text, with a format that can be converted to audio, using magnetic media, optical media, electronic media or internet services and resources, (ii) printed in Braille or (iii) printed in enlarged fonts. Anvisa has also created an electronic medication leaflet databank, having the digital leaflet finally being regulated under Law #14,338/22.

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1.2. Medication leaflets and the controversy of skinny labeling

RDC Rule #47/2009 defines “standard leaflet” as the standard information aimed at harmonizing the leaflets of specific, herbal, generic, and similar medicines, with the contents being published in the electronic leaflet. For specific and herbal medicines, standard leaflets are prepared by Anvisa. As for generic and similar medicines, the standard leaflets are those of the medicines chosen as reference medicines and that contain all information derived from every clinical study conducted by or for the manufacturer. Consequently, the medication leaflets of generic medicines are expected to fully align with the provisions of those from innovative or reference medicines, typically under patent protection.

However, therein lies a considerable controversy, as the leaflet for generic medicines is required to mirror that of innovative or reference medicines.

According to studies, the pharmaceutical research industry invests up to US$4.2 billion in pre-clinical and clinical research, spanning several years. This investment aims to develop new molecules that bring added value to patients' lives or well-being, having also an acceptable safety profile and commercial viability. However, the exclusivity guaranteed by patents lasts only 20 years from the filing date with the BRPTO, not from the approval date of the patent application, significantly limiting said patent protection.

Conversely, the generic industry eagerly awaits the expiration of patent protection to expedite the commercialization of their products, given the need for high sales volumes to compensate their substantially lower profit margins. Now, one may wonder, how does this relate to the medication leaflet?

The answer is straightforward. Some medicines are subject to second-use patents, wherein the product is covered by multiple patents, each pertaining to a specific use. At times, one of these patents may expire while the second one remains in force. Consequently, certain makers of generic medicines typically omit any reference to therapeutic indications still protected by the second, active patent. They do so to justify the commercialization of the medicine by asserting that they are not infringing the patent.

This practice is known as “skinny labeling”, “skinny label”, or “carving out”. Essentially, this concept bypasses the need to harmonize with the medication leaflet of the innovative or reference medicine. Notably, any change in the leaflets of innovative or reference medicines must be mirrored in those of generic or similar medicines. The timeframe for this is up to 180 days, as per Anvisa’s RDC Rule #73/2016.

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1.3. ANVISA changes the regulation of medication leaflets harmonization

On December 11, 2023, after Consultation on Public opinion #1,137/2022, Anvisa issued RDC Rule #831/2023, dated December 6, 2023, which came into effect on February 8, 2024. This Rule introduced a significant change to RDC Rule #47/2009, specifically by incorporating new provisions into the third and fourth paragraphs of Article 14 and stipulating that the leaflets of generic and similar medicines may deviate from their respective standard leaflets concerning indications protected by patent or claimed in published patent applications. In such instances of deviation, the leaflets of generic and similar medicines must include the bolded phrase “The information referring to the indications of the patent-protected medicine has been suppressed,” inserted in section “1. WHAT IS THIS MEDICATION INDICATED FOR?” of the patient’s leaflet and “1. INDICATIONS” in the healthcare professional’s leaflet.

With this decision, Anvisa acknowledges the possibility of "skinny labeling," despite widespread criticism and global controversy surrounding the practice, including staunch legal opposition.

Anvisa's rationale for this decision not only took into account the public consultation mentioned earlier but also asserted that it purportedly broadens the population's access to medicines, given that it provides multiple options for specific therapeutic indications that are no longer protected by patents.

This decision by Anvisa once again brings to light the conflict between granting second-use patents and the practice of skinny labeling. Considering the hierarchical relationship between legal and infra-legal norms, it is likely that this matter will persist in generating significant debate in Brazilian courts until legal precedents are firmly established.

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