Biological and Biosimilar Drugs

Originating from a highly complex chemical nature (unstable, with a three dimensional structure, high molecular weight and heterogeneous biological nature, amongst other features) and synthesized from living organisms, biological drugs have been gaining prominence as one of the main, if not most important, sources of innovation in the pharmaceutical field, and currently represent a significantly relevant portion of the drugs available on the market.

Research in this field of technology has resulted in a revolution in the treatment of several diseases, enabling the development of treatment options for numerous complex ailments, chronic and even rare, the treatments for which were not available or even effective for all types of patient.  This is why the biotechnology industry has become the main source of new drugs, and also of great social and economic importance, due to the need for skilled labour with specific technical knowledge, which, in turn, promotes research and generates jobs.

Naturally, one of the targets of the generics industry is also to apply the same principles to these biological drugs as are applied to conventional drugs.  However, the reproduction of biological drugs – as commonly occurs with conventional chemical drugs –is not feasible, at least at the moment, due to their high complexity and laborious manufacturing process, amongst other aspects.  On the other hand, it is possible to obtain similar new biological drugs, which are usually designated biosimilars.

A biosimilar  drug is a secondary version (not new) and subsequent to an original biological drug, for which the permission to sell has previously been obtained from the Regulatory Authority.

The World Health Organization (WHO), in conjunction with other international regulatory agencies, has performed its role aiming to create and establish scientific standards and mechanisms that ensure the safety, efficacy and quality of biological drugs that are produced worldwide.  Moreover, there is also concern regarding regulation in respect of establishing that drugs of a biological nature cannot be “copied”.

In Brazil, the National Health Surveillance Agency (ANVISA) has regulated the registration of generic products since 2003 (Resolution No. 135 of May, 2003) and determines that biological products derived from plasma or human blood, and biotechnological products, with the exception of antibiotics and fungicides, are not allowed to be registered as generic .

ANVISA also has a normative framework for the registration of biological products, initially established by Resolution nº 80/2002, and currently regulated by Resolution nº 55/2010, which sets out minimum requirements for quality, safety and efficacy for these drugs.

Conceptually, the European Medicines Agency – EMA and ANVISA adopt similar systems, differing only in terms of nomenclature.  ANVISA uses the definitions “new biological products” (biological drugs with a known biological molecule, not yet registered in Brazil) and “biological products” (an identical definition to that of “new biological drug”, however this refers to a particular molecule that has already been registered in Brazil). New biological products must be registered in the classic regulatory way, with the submission of a complete dossier containing all the production data, quality control and complete non-clinical and clinical data (Phase I, II and III).  For biological products (non-innovative), there are two possible regulatory paths to registration: that of development by comparison, and that of individual development. In both cases, it is possible to submit a registration dossier with reduced information, with some clinical tests being required.
Law #. 10,603 restricts the protection of undisclosed information submitted for the approval of selling products for veterinary use, fertilizers, pesticides, their components and related products.  However, there is the possibility of disputing or claiming the same protection for pharmaceutical products by bringing legal proceedings, by analogy with the provisions of the said Law.

With respect to patent protection, drugs are patentable under the Industrial Property Law (IPL) # 9,279/1996.  There is no restriction in the IPL with regard to the protection of biological drugs.  Thus, as long as they meet the requirements for patentability of novelty, inventive step and industrial application, as listed in Articles 8, 11, 13 and 15 of the IPL, these drugs, as well as their manufacturing/improvement methods, in addition to kits and pharmaceutical compositions/combinations that contain them, are also fully entitled to patent protection in Brazil.

1 Also known in Europe as “non-innovative biopharmological”, and in the US as “Follow-On Protein Product” or “Follow-on Biologic”, in Canada as “Subsequent-Entry Biologics” and by the WHO as “Similar Biotherapeutic Product”.
2 (…) IV – Drugs that will not be accepted as generic
For the purposes of registering a generic drug, the following will not be allowed: (…)
3. biologics, immunotherapy, derived from plasma and human blood;
4. products obtained through biotechnology, except antibiotics, fungicides and others, at the discretion of ANVISA; (…)”