INTERCHANGEABILITY (biologics and biosimilars) – Technical Note No. 60/2026 and the new chapter on the topic in Brazil
The Brazilian Health Regulatory Agency (“Anvisa”) published Technical Note No. 60/2026/GGBIO (“Technical Note No. 60/2026”), through which it consolidated its current understanding regarding the interchangeability of biosimilar drugs and their respective comparator biologics. The document details the ongoing progress of the regulatory debate on the topic and reinforces the Agency’s alignment with the positions of leading regulatory authorities, such as the European Medicines Agency (“EMA”), the Medicines and Healthcare Products Regulatory Agency (“MHRA”), the Food and Drug Administration (“FDA”), and the World Health Organization (“WHO”).
The Technical Note reaffirms Anvisa’s understanding that interchangeability is possible, provided that, for example, approved conditions of use and appropriate pharmacovigilance and traceability mechanisms are observed.
The Evolution of Interchangeability at Anvisa
Historically, the interchangeability of biosimilars and biologics has always been treated with caution by regulatory authorities and healthcare professionals, particularly due to concerns regarding immunogenicity and the potential clinical impacts resulting from switching between drugs of this nature.
The evolution of this discussion necessarily involves the evolution of interchangeability among synthetic reference drugs, similar drugs, and generic drugs.
Until 1999, synthetic reference drugs were not considered interchangeable with similar drugs (and the concept of interchangeability was first introduced that year through Law No. 9,787/1999, which addressed generic drugs). From 1999 to 2015, reference synthetic drugs became interchangeable only with generic drugs, while remaining non-interchangeable with similar drugs. Since 2015, and particularly following the enactment of Federal Law No. 13,235/2015 (which amended Law No. 6,360/1976 to bring the quality control standards for similar drugs in line with those for generic drugs), reference synthetic drugs have become interchangeable with both similar drugs and generic drugs. Similar drugs and generics, however, remained non-interchangeable.
As health legislation continued to evolve, Resolution RDC No. 55/2010 introduced, that year, the concepts of “new biological medicines”—the “innovators”—and “non-new biological medicines”—the “biosimilars.” That regulation, however, did not address issues that remain highly relevant today: it failed to address interchangeability, bioequivalence, and therapeutic equivalence. Much of this was because, at that time, the debate—including the scientific one—was still progressing at a slow pace.
Therefore, the issue of interchangeability of biological medicines (whether new or non-new; reference or biosimilars) has always been a challenge.
In June 2017, Clarification Note No. 003/2017/GPBIO/GGMED/ANVISA was published, subsequently revised in October 2018, addressing the following topics: (i) it introduced a concept of “interchangeability”; (ii) a concept for “substitution” was presented; and based on these concepts, it was stated that (iii) interchangeability and substitution would not be automatic; (iv) both would be more directly related to clinical practice than to regulatory status; (v) physicians could opt for substitution whenever supported by scientific studies; (vi) ANVISA would include information on the studies presented in the registration dossier in order to assess interchangeability; and (vii) multiple switches between biologics and biosimilars would not be recommended.
Also in 2018, the Ministry of Health established the “Working Group for the Discussion and Formulation of the National Policy on Biologics within the Unified Health System,” and ultimately concluded that (i) it was not possible to make an explicit and general recommendation regarding the interchangeability of biologics and biosimilars; (ii) additional scientific studies and a dedicated pharmacovigilance system for biologics would be necessary; and (iii) multiple switches were not recommended.
At that time, therefore, the Ministry of Health’s objective was to address—in a timely manner and based on scientific evidence—for each specific drug and each therapeutic indication, the impossibility, the possibility, or the safe methods of automatically substituting an innovative biologic with a biosimilar.
In this historical context, the current Technical Note (No. 60/2026) aligns with the position adopted by other foreign agencies, such as the EMA, the FDA, the MHRA, Health Canada, and the World Health Organization. Below, we highlight the main points of the new Technical Note published by Anvisa, which now provides guidance on the topic of interchangeability.
Key Points of Technical Note No. 60/2026
Right at the outset, the Technical Note emphasizes that the topic addressed therein reflects current technical knowledge and up-to-date international references—that is, those in effect at the time of its publication. This is because, as noted in the brief historical overview above, the discussion has been expanding and evolving over the past few years (and is likely to continue to be revised).
For the purposes addressed in the Technical Note, the following concept of interchangeability was adopted: “interchangeability refers to the scientific and regulatory recognition that two drugs can be used interchangeably with the expectation of the same clinical effect.”
Based on this, and considering that there are “doubts regarding the safety and efficacy of treatments in situations where the comparator biologic and its biosimilars are alternated,” the following was established:
- Biosimilars offer the same therapeutic benefits as their reference biologics;
- Switching between biosimilars and their reference biologics is safe and effective, with no clinically relevant impact on efficacy, safety, or immunogenicity;
- International experience indicates that switching between the reference biologic and the biosimilar does not clinically significantly alter the safety, efficacy, and immunogenicity profiles when performed in accordance with the conditions of use approved by the health authority and the product characteristics; and
- For this to occur on a regular basis, the following elements are essential when switching between the comparator product and biosimilars, and between biosimilars:
- Clear and transparent communication with patients;
- Education and training for healthcare professionals, managers, and decision-makers through guidelines that address the needs of the transition process, supporting the use of approved products in clinical practice in accordance with their approval characteristics
- Documentation of the change made;
- Ensuring traceability (unambiguous identification of the product and lot); and
- Clear information in the prescribing information for healthcare professionals.
Its main contribution is to formalize the understanding that interchangeability stems from the demonstration of biosimilarity itself.
According to Anvisa, the body of evidence required for regulatory approval of a biosimilar would be sufficient to support the expectation that switching between the comparator biologic and its biosimilar—or between biosimilars that share the same comparator—will not result in clinically relevant differences.
The Technical Note emphasizes that the evaluation conducted during the registration process would already be sufficient to provide a sound scientific basis for supporting the interchangeability of approved products.
Given the impact of this understanding on the regulated sector, we will continue to monitor this issue and its potential developments.
This material is for informational purposes only and should not be used in isolation for decision-making. Specific legal advice may be provided by one of our attorneys. Copyright is reserved by KESTENER VIEIRA TORRONTEGUY SPEGIORIN ADVOGADOS.
