The Brazilian Health Regulatory Agency (Anvisa) has introduced RDC 964/2025, a new guidance that outlines in more detail the requirements for conducting forced degradation studies. This new regulation replaces RDC 53/2015, aligning the requirements for forced degradation studies with international (ICH) standards.

At Lhasa we are keen to support our members working in this field with providing information and support around the updated requirements. RDC 964 allows for greater flexibility in justifications based on scientific rationale, theoretical studies, and supporting evidence. This is where our solution for understanding forced degradation pathways, Zeneth can provide valuable support.

Keep reading to explore the key updates in the new guidance and how Zeneth can assist companies submitting to Anvisa.

Comparison of RDC 53/2015 and RDC 964/2025

Similarities:

• Both establish guidelines for forced degradation studies, covering the identification and qualification of degradation products.
• Applicability remains focused on medicines with synthetic and semi-synthetic APIs (active pharmaceutical ingredients), excluding biological products, herbal medicines, and excipients.
• Requirements include conducting degradation studies on at least one batch of the drug, including both the API alone and in the final formulation.
• Consistent stress conditions are required, including exposure to heat, humidity, acid, base, and oxidising solutions.

Differences:

• Removal of the obligation to degrade 10% of the API :
  As long as it can be demonstrated that all relevant degradation chemistry is shown, there is no longer a need to ensure 10% degradation of the API.
• Enhanced evaluation of results: Additional requirements now include:
  • Proof that the stability-indicating method is suitable,
  • Demonstrating the chromatography peaks are pure.
• Additional oxidation requirements: Auto-oxidation experiments with radical initiator reagents are now required, increasing the number of oxidation tests from two to three (peroxide, metal, and auto-oxidation).
• Scientific justifications accepted for testing exemptions: Liquid-phase studies for solid pharmaceutical forms may be left out if overall the forced degradation study results demonstrate stability.
• Mass balance justification: Previously, Anvisa accepted mass balance deviations only in specific cases. RDC 964/2025 now allows for more scientific justifications in explaining deviations.

5 Ways Zeneth Supports Compliance with RDC 964/2025

1. Prediction of degradation chemistry
   RDC 964/2025 states that the technical discussion related to the forced degradation studies should also include conclusions about the main degradation routes of the API(s), the monitored degradation products and the suitability of the analytical method. Zeneth can support the design and justification of the forced degradation studies by providing an overview of the potential degradation chemistry of the API or drug product under the selected conditions.
2. Identification of potential degradation products
   Zeneth facilitates the characterisation of peaks observed in analytical results by predicting the structures of potential degradation products. This helps inform method development by understanding the potential for co-elution, based on the properties of the predicted compounds.
3. Support for auto-oxidation studies
   With the inclusion of auto-oxidation in RDC 964/2025, Zeneth covers multiple types of oxidation transformations. This ensures companies can scientifically justify their forced degradation study results in compliance with the updated guidelines.
4. Providing justifications for regulatory submissions
   ANVISA may request comprehensive scientific justification of a forced degradation study for further clarification. Zeneth can support the justifications needed by providing an overview of expected degradation chemistry and realistic mechanistic routes for any detected impurities.
5. Justification of mass balance deviations
   By providing a comprehensive understanding of degradation pathways, Zeneth can help support explanations for mass balance deviation when required.

Senior Global Alliances Manager at Lhasa, Diego Gomes, summarises that ‘The introduction of RDC 964/2025 brings Anvisa’s regulatory requirements in line with international standards for forced degradation studies, which require a comprehensive scientific understanding of the drug product, with room for more scientific justification to be presented as part of the assessments. Using Zeneth can support submissions by providing strong scientific rationale for the impurity profile of your API or drug product.’ Get in touch with our team if you would like more information about Zeneth.

Last Updated on March 25, 2025 by lhasalimited