On August 26, 2026, ANVISA published Normative Instruction (IN) No. 467/2026, amending IN No. 258/2023, that defines the List of Qualified Impurities and their respective limits for the marketing authorization and post-authorization of medicinal products, in accordance with the criteria for impurities classification provided in subsection III of Article 19 of Brazilian Guideline – RDC No. 964/2025.

What IN No. 258/2023 establishes

IN No. 258/2023 lists, for a set of active pharmaceutical ingredients, the impurities and degradation products already qualified by ANVISA — typically because they correspond to significant metabolites identified in human or animal studies, or because they are supported by robust scientific literature data. 

Impurities listed in the Annex, at or below the published limits, are considered qualified and are exempt from filing a specific amendment related to qualification of impurity and degradation product, representing a simplification for pharmaceutical industries, since it avoids the need for dedicated qualification studies and submissions.

The guideline provides the drugs, their qualified impurities, the CAS number, the route of administration, the reference maximum daily dose (MDD), the qualified limit (in percentage and in milligrams), and the technical rationale supporting the qualification.

The adoption of predefined limits for qualified impurities streamlines the processing of submissions related to marketing authorization and post-authorization of drug products and rationalizes the authority’s workflow, helping to reduce delays in critical processes.

What changes with IN No. 467/2026

The update published in August amends Article 1 of IN No. 258/2023, updating the legal basis underlying the List of Qualified Impurities: the qualification criteria now expressly reference items III of Article 19 of Brazilian Guideline – RDC No. 964/2025, replacing Article 10 of RDC No. 53/2015, which is hereby revoked. In practice, this first change realigns IN No. 258/2023 with the regulatory framework currently in force for impurity qualification.

In addition, IN 467/2026 republishes the Annex to IN 258/2023 with a significant expansion of the list: 17 impurities related to 17 APIs have been added. With this update, the consolidated list now includes 46 qualified compounds—a 58% increase compared to the 25 listed in the previous revision, implemented by IN 337/2024. 

Points of attention for the pharmaceutical companies

For companies already relying on the List, the update carries two distinct types of impact: the legal basis change is a reference correction with no immediate practical effect, while the expanded Annex can directly affect ongoing dossiers, who can now benefit from the exemption from a dedicated impurity qualification amendment.

It is important to highlight that including an active pharmaceutical ingredient on the List does not automatically approve specification limits for the drug product. As IN No. 258/2023 itself establishes, approval of these specification limits remains subject to compliance with current Guidelines for marketing authorization and post-authorization variations, including supporting justifications for the proposed specification and analytical validation data consistent with the limits sought. It should also be noted that it is necessary to comply with all other Guidelines applicable to the establishment of impurity limits, published by ANVISA and ICH.

Likewise, new evidence that could alter the published information or limits must be filed under a specific subject code — and ANVISA may, at any time, remove an impurity from the List or revise its limit to more restrictive values, with an adaptation deadline to be published alongside the update.

IN No. 467/2026 came into force on the date of its publication, i.e., August 27, 2026.