On October 5, 2026, ANVISA’s General Management of Medicines (GGMED) signed Technical Note (NT) No. 233/2026/SEI/GGMED/DIRE2/ANVISA, which addresses the possibility of reclassifying synthetic medicinal products that are analogs of biological products into the similar (branded generics) category. The document clarifies the regulatory effects of the current classification of these products, authorized as new medicinal products under Resolution RDC No. 753 of September 28, 2022, and proposes an optional flow for companies that wish to change category. The change in regulatory classification is intended to make the drug eligible to serve as the matrix product for a simplified marketing authorization procedure (“clone”). According to the NT, the initiative also responds to the high and growing number of questions the General Management has received on the topic.

Why these products are classified as new medicinal products

In Brazil, biological products cannot be reference medicinal products. As a result, a synthetic analog of a biological peptide cannot initially be authorized as a generic or a similar (branded generic) and follows the new medicinal product pathway (analog API), as defined in RDC No. 948 of December 12, 2024. The NT notes that this pathway has been used for synthetic analogs of peptides such as semaglutide, liraglutide, and teriparatide.

The data package for these applications is particular. In general, it does not involve clinical studies and focuses on demonstrating that the active pharmaceutical ingredient (API) has the same chemical structure (primary, secondary, tertiary, and higher-order) and the same biological activity as the biological comparator. For relatively complex peptides of 20 to 80 amino acids, this demonstration ensures that the synthetic analog is the same peptide, spatially organized in the same way and interacting with receptors in the same manner.

Interchangeability and simplified marketing authorization: where the impasse arises

Interchangeability is an exceptional concept in Brazilian health law and depends on express regulatory provision. An interchangeable medicinal product does not merely show that it is safe and effective: it shows the same efficacy and safety claims, under the same conditions, for the same population. For this reason, two medicinal products with the same active ingredient, pharmaceutical form, and strength but with independent clinical studies may be safe and effective without necessarily being interchangeable with each other. Interchangeability requires demonstrating the same pharmacokinetic behavior, through a relative bioavailability study or a biowaiver, depending on the pharmaceutical form.

The current framework provides for interchangeability between a generic medicinal product and its reference medicinal product, and between an interchangeable similar medicinal product (branded generic) (RDC No. 58 of October 10, 2014) and its reference medicinal product. There is no provision for other categories: not between biological products and synthetic medicinal products, even analogs, nor between different new medicinal products.

This connects to the simplified marketing authorization procedure, the so-called “clones,” governed by RDC No. 954 of December 20, 2024. The procedure requires a suitable matrix application, and one of the criteria for selecting the matrix medicinal product (Art. 4, item II, subitem b) is that it be therapeutically equivalent to a reference medicinal product.

The result is an impasse: only one of the synthetic analogs, the first one marketed, can be listed in the Reference Medicines List (LMR) and serve as a matrix. The others, authorized as new medicinal products, cannot be used as a matrix for simplified marketing authorizations, which creates a potential perception of lack of equal treatment and a possible limit on product availability and broad competition.

Technical rationale: why the NT sees particularities in these products

For synthetic analogs of peptides, the NT states that the demonstrations required for marketing authorization cannot be considered demonstrations of interchangeability. The reason is that, in these cases, the main proof of efficacy and safety is structural identity. In addition, bioequivalence studies are generally not conducted, because these products are parenteral solutions eligible for a biowaiver.

Two other points weigh on the analysis. The first is the impurity profile, which in chemically synthesized peptides tends to be very different from that of products obtained by biological methods. Residual solvents follow the limits of the ICH Q3C guideline, and elemental impurities follow ICH Q3D. What remains are peptide-related impurities and aggregates, for which ANVISA uses guidelines from equivalent foreign agencies as a reference, such as the FDA’s product-specific guidances for liraglutide and semaglutide. The NT stresses that differences in impurity profile do not prevent interchangeability, even among synthetic medicinal products, as long as the safety of each impurity is within accepted limits (RDC No. 964/2025 or the ICH Q3A and Q3B guidelines).

The second point is the delivery device, common in these products in the form of self-injection pens. Dose accuracy, differences in the method of administration, and human factors in device activation are part of the analysis, and the presence of a device does not by itself prevent interchangeability if the devices are compared and found equivalent in dose precision and accuracy.

The optional reclassification flow

The flow applies to synthetic analogs of biological products that have been or will be authorized as new medicinal products but were not included in the LMR because another product with the same active ingredient, strength, and pharmaceutical form was listed earlier, and that wish to become similars and, therefore, be able to generate clones. The NT organizes it in four steps:

• The marketing authorization holder (MAH) assesses the possibility and its interest in becoming an interchangeable similar medicinal product (branded generic).
• If interested, it submits a statement through ANVISA’s “Fale Conosco” contact channel, addressed to GGMED and citing the NT.
• GGMED evaluates the request and, if the marketing authorization is valid and the reference medicinal product has been duly selected, opens an application in the product’s reclassification process. By official letter, it requests from the company a pharmaceutical equivalence study with the reference medicinal product within 24 months (Art. 35, § 3, of RDC 753/2022) and notifications of package leaflet and labeling changes within 30 days, so that the leaflet follows the standard leaflet (RDC No. 47/2009) and the labeling becomes that of a similar medicinal product, without a change in brand name or marketing authorization number.
• Once the application is opened and the letter is sent, the product is considered a similar and may serve as a matrix for clone marketing authorizations under RDC 954/2024, provided the other provisions of that regulation are met.

The flow is optional, and maintaining the product as a new medicinal product prevents its use as a matrix for simplified marketing authorization. The NT also stresses that the flow is based on regulations already in force and does not change existing obligations, such as the requirement that the similar medicinal product’s leaflet fully comply with the standard leaflet and the post-approval change rules of RDC No. 73/2016.

What changes in practice and points of attention

For those who already hold a synthetic analog authorized as a new medicinal product and outside the LMR, the decision is strategic: remain a new medicinal product, with no possibility of serving as a matrix, or migrate to the similar (branded generic) category, taking on the pharmaceutical equivalence study within 24 months, the leaflet and labeling changes within 30 days, and full alignment with the standard leaflet. For those who plan to register clones, products migrating to similar status tend to widen the matrix options, always subject to the other conditions of RDC 954/2024.

Some points deserve monitoring. The NT does not detail the consequences of a possible failure to meet the 24-month deadline, and the flow depends on there being a duly selected reference medicinal product. The market context is also worth noting: in CMED’s 2025 Statistical Yearbook of the Pharmaceutical Market, GLP-1 agonist antidiabetics appear among the subclasses with revenue above R$1 billion, concentrated in only three companies, and the NT itself cites broad competition as one of the flow’s objectives.

How Vita can help

Deciding whether to reclassify a product requires looking at the regulatory, technical, and commercial aspects at the same time. Vita works with regulatory strategy and intelligence, supporting companies in assessing the best marketing authorization pathway for synthetic analogs of biological products, in planning the pharmaceutical equivalence study and the leaflet and labeling notifications, in aligning with the standard leaflet, and in planning simplified marketing authorizations from a new matrix, with gap analysis and regulatory life cycle management. Companies interested in understanding how NT 233/2026 may affect their products and projects can count on Vita.