Biological drugs are produced from living cells and, therefore, are more complex structures and have high production costs. Currently, they are the biggest source of innovation in the pharmaceutical market, in addition to being able to treat several diseases that until then had no effective treatments. Among biological medicines are vaccines, enzymes, hormones, anticoagulants, etc.

Due to their highly specialized production process, biological medicines – as well as biosimilars, which are developed based on a reference biological (also called original) – have a regulatory process that is also specific.

Regulation of biological products

The regulation of biological and biosimilar medicines is made by the National Health Surveillance Agency (ANVISA), which requires:

• Certificate of Good Manufacturing Practices issued by ANVISA;
• Complete dossier, with data on development, production, quality control and clinical and non-clinical studies;
• Legal and technical documentation;
• Technical, therapeutic experimentation, pharmacovigilance and immunogenicity study reports;
• Products manufactured abroad must have been registered and released for use in their country of origin or manufacture.

Specifics of regulation of biosimilars

Unlike a generic drug, biosimilars (which needs to be produced with the same active ingredient as the original), due to all the complexity involved in the development of biological drugs as a whole, are not identical to the product used as a reference. Therefore, they also need to follow some specific criteria at the time of regulation.

Brief history of regulation of biosimilar medicines

Due to all the particularities involved in the development of this type of drug, several countries have started to establish specific regulatory processes for them. The first region to establish a regulatory pathway for approval of biosimilar medicines was the European Union, in 2005.

In 2009, the World Health Organization (WHO) released guidelines and recommendations for the approval of biosimilar medicines. WHO’s objective was that this document, if not adopted as a whole, would serve as a basis for countries to create their own regulatory pathways. In Brazil, the norm for the regulation of biosimilar medicines came into force in 2010.

Points common to all standards

International regulations regarding biosimilar medicines have some variations and specificities, according to the marketplace in which they are inserted. However, there are some fundamental points that are common to all of them. The main ones are:

• Biosimilars must be evaluated based on extensive documentation, covering points related to manufacturing, efficacy, safety and quality;
• Pharmacovigilance programs, which must be implemented after approval of the product, must also be presented, together with the application for registration of the biosimilar medicine;
• It is essential to have comparative studies that show the differences between the biosimilar and the reference biological, following equivalence or non-inferiority methodologies;
• It is also necessary to investigate immunogenicity, that is, the drug’s ability to cause an immune response in the patient’s body;
• The regulation of biosimilars should not follow the same rules in force for generic drugs.

Regulation in Brazil

An important particularity of the Brazilian standard concerns the nomenclature of biologicals, which are called simply by ANVISA as new (innovative) and non-new (biosimilars) biological medicines.

In addition, biosimilars (or non-new biologicals) can be approved by two different routes:

• Comparability route: in this case, manufacturers that submit biosimilars for approval by ANVISA must present comparative studies between it and the reference biological product. As it is impossible for the biosimilar to be identical to the original biological, the aim of these studies is to show that possible differences between the two do not interfere with its quality, safety and efficacy;
• Individual copy: a reduced dossier, similar to that required for the analysis of new biological medicines, must be presented, without the need for comparative information.

A ANVISA also uses guides with specific guidelines for each class of products, a practice inspired by the European model.

In addition to facilitating the process of incorporating this type of technology, the development of biosimilars tends to lower the production costs of biological medicines. As a result, a lower final price of the product and easier access to this type of treatment for patients is expected.

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