Biosimilars & Biologics
Biosimilars & biologics in Brazil – a comprehensive legal overview. Prepared in association with Trench, Rossi e Watanabe one of Brazil’s most prestigious law firms, this is an extract from The Pharma Legal Handbook: Brazil, which can be purchased for USD 99, here.
1. Are biosimilar medicines considered the same as generic medicines in your country?
No, a biosimilar drug is not considered to be the same as a generic drug. There are specific rules governing generic and similar drugs, and they are solely applicable to synthetic drugs, and not to biologicals, which are ruled by a specific resolution.
For biological products, ANVISA’s Resolution RDC No. 55/2010 determines that there are two types of products: “new biological products” (for products not registered before ANVISA yet) and “biological products” (for the products that are not new or that contain an already known molecule of biological nature).
Note, however, that the rules establish two different routes to register “biological products”: by comparison, which, by definition, “is the scientific comparison, with respect to non-clinical and clinical parameters in terms of quality, efficacy and safety, of a biological product with a comparator biological product, in order to establish that there are no detectable differences in terms of quality, effectiveness and safety between the products” and by individual pathway, defined as “the regulatory route that may be used for obtaining the registration of a biological product in which it is necessary to present total data on development, production, quality control and non-clinical and clinical data to demonstrate quality , efficacy and safety of the product”.
Thus, despite the fact that Brazilian legislation does not adopt the wording “biosimilar”, but only “new biological products” and “biological products” (for the products that are not new or that contain an already known molecule of biological nature), “biosimilar” is the “biological product” registered by comparison pathway.
2. Are all biologic medicines, including biosimilar medicines patentable in your country?
Biologic and biosimilar medicines are generally patentable in Brazil, provide they comply with patentability requirements, such as novelty, inventive step and industrial application.
Federal Law No. 9.279/1996 (Brazilian IP Law) also establishes, however, that biological materials, when found in nature or isolated therefrom, are not considered inventions (Article 10, IX, of the Brazilian IP Law). For this reason, biological materials such as nucleic acids, antibodies and vectors can only be patented if they comprise human-induced modification(s) in their genetic composition.
In addition, natural living beings (animals and plants), in whole or in part (such as cells), even if modified/recombinant ones, cannot be patented under Article 18, III, of the Brazilian IP Law. However, this does not exclude the possibility of having transgenic microorganisms, such as bacteria, protozoa, virus, and yeasts protected by a patent. For the purposes of the IP Law, transgenic micro-organisms are organisms, except the whole or part of plants or animals, that exhibit, due to direct human intervention in their genetic composition, a characteristic that cannot normally be attained by the species under natural conditions.
3. Is there a specific regulatory framework for the marketing authorization of biosimilar medicines in your country? If yes, what is the regulatory framework for the authorization of biosimilar medicines?
Yes. ANVISA’s Resolution RDC No. 55/2010 is the main rule governing biologicals.
4. What kind of data package is needed to obtain approval for a biosimilar drug? Is this any different to the requirements for the original Biologics drug?
To obtain approval for a biologic drug (new biological product), it is necessary to submit to ANVISA documents about the company (such as the Sanitary Authorization and the Certificate of Technic Responsibility) and about the drug (such as its pharmacovigilance data, identification code and specifications). It is also necessary to submit in the same proceeding a technical report, a therapeutic experimentation report and a pharmacovigilance report in order to detail every methodological, clinical, operational and functional aspect of the biologic drug. If the product is blood derivative, biotechnological or if it is a vaccine, certain specific documents are also required.
In reference of the biosimilar drugs (biological products), the requirements follow the original biologic drug pattern, except as follows:
For biological products registered by individual pathway: The dossier required is the same aforementioned, but, in this case, the extension of the non-clinical studies can be reduced, depending on the complexity of the molecule. In addition, the clinical studies in its phases II and I are not mandatorily comparatives. Studies phase III are always necessary (and comparative). If available, the results of step IV must be submitted.
For biological products registered by comparison pathway: The dossier required is the same as aforementioned, with the addition of a data report about the biologic product and its comparator.
5. What are the requirements for the choice of the reference comparator product?
The comparator product is defined as the already registered biological product, based on the submission of a full dossier, and which has already been commercialized in Brazil.
The comparative pathway may be used when comparability between the biological product/biosimilar and the already registered biological drug is possible with regards to quality, efficacy and safety. This pathway will require the submission of a comparative dossier containing non-clinical and clinical studies in order to demonstrate comparability between the biological product to be approved and the comparator one. It also requires the submission of studies with information about development and quality control and a comparability result report (providing a comparison to the comparator drug), among other requirements.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
No, the comparator product must be registered before ANVISA.
7. How are the prices of biosimilar medicines regulated? Is this any different to the requirements for the original Biologics drug?
The prices of biological products are regulated by Brazilian Drug Market Regulation Chamber (“CMED”), through the specific parameters defined in Communication No. 9/2016.
The prices applicable to the drugs that evidence therapeutic gain, the price cannot be higher than the lowest price practiced for the same product in United States, New Zealand, Australia, Greece, Portugal, Italy, Spain, France, and Canada.
For drugs that do not evidence therapeutic gain and that are new to company’s portfolio, the price will be defined based on the average cost of treatment with drugs with a similar molecule, considered revenues, and cannot, in any case, be higher than the lowest price practiced for the same product in United States, New Zealand, Australia, Greece, Portugal, Italy, Spain, France, and Canada.
For drugs that do not evidence therapeutic gain but in case the company already has in its portfolio of commercialized products a product with similar molecule, the price will be defined based on the average cost of treatment with drugs marketed by the company itself.
For new presentations of drugs already marketed by the company with the same trademark, the price will be defined based on the average cost of treatment with the same drug.
8. What is the reimbursement policy for biosimilar medicine? Is this any different to the requirements for the original Biologics drug?
Yes, the reimbursement is possible but there is no specific policy. Note, however, that according to court precedents on Federal Law No. 8,080/1990, known as the Brazilian Organic Health Law, the payment or reimbursement of national or imported drugs that are not registered before ANVISA is prohibited. There is no difference to the requirements for new biological products and biological products.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
10. What is the legal framework for biosimilar medicines prescribing (clinical decision maker) and dispensing (pharmacy level, hospital or retail)? Is this any different to the requirements for the original Biologics drug?
There is no legal framework specific for prescribing and dispensing of biological products. The physician is free to prescribe the treatment he/she considers appropriate to the patient.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
The physician is free to change the treatment of his/her patient, since duly justified. However, pharmacy cannot change patients’ prescription.
ANVISA issued a note regarding interchangeability and it considered the evaluation regarding the possibility of switch must be done by the involved physician, on a case-by-case basis, considering the patient and its particularities.
12. What are the post – authorisation requirements (including pharmacovigilance, risk management plans, post-approval studies) for biosimilar medicines? Is this any different to the requirements for the original Biologics drug?
Companies must maintain a pharmacovigilance system in order to ensure the monitoring and evaluation of the safety and efficacy of the drug. There are no differences regarding the requirements for new biological products and biological products.
ANVISA issued a note regarding interchangeability of biologicals and it considered that, although the medical evaluation if mandatory, multiple switches between biological products and the comparator biological product are not adequate, as it jeopardizes the traceability and use monitoring.
13. Are there specific policies and requirements in terms of biosimilar medicines labelling in the event of second medical use patents? Is this any different to the requirements for the original Biologics drug?
No, there are no specific policies.
14. Have there been any significant legal/judicial developments in relation to biosimilars in your country? (Including but not limited to IP, procurement, competition, misleading information campaign, access to reference comparator product)
ANVISA updated in 2018 a note that was initially issued in 2017 regarding interchangeability of biologicals. ANVISA considered that patient’s medical evaluation is mandatory and that the physician is responsible for deciding which products is appropriate to each situation, according to product’s characteristics, existent pathology, individual response and each patient’s treatment history. In view of this, ANVISA expressed that it is not considering classifying biological products as interchangeable or not.
15. Are there proposals for reform or significant change to the legal, regulatory, procurement of biosimilars? If yes, when are they likely to come into force?
The only Bill we identified in relation to biological products is Bill No. 5415/2019 and its purpose is to include new articles to the Federal Law No. 8,080/1990 for prohibiting the dispensation of biological products in the Unified Health System (“SUS”) to a patient that is in ongoing treatment with the new biological product without previous consultation to patient’s physician.
As Bill’s proposition is very recent (dates from October, 2019), it is not possible to estimate if and when it will be approved.