Overview
The National Health Regulatory Agency (ANVISA) has published a new set of guidelines regarding the classification, identification, and control of impurities and degradation products in medicines. This update is crucial for the pharmaceutical industry as it establishes clearer and more rigorous criteria for demonstrating product safety and quality. The focus of the new guidelines is to harmonize national practices with international guidelines and ensure that acceptable limits for these substances are consistently monitored throughout the drug’s lifecycle, from production to expiration date.
Introduction
The Importance of Impurity Control
Impurities and degradation products are substances present in the drug that are not part of the Active Pharmaceutical Ingredient (API) or excipients, and may arise during synthesis, storage, or manufacturing. If left uncontrolled, these substances can affect efficacy, safety, and, in extreme cases, pose a toxicological risk to the patient (such as the case of nitrosamines, which triggered global alerts).
Historically, impurity control has been an area of constant regulatory evolution. ANVISA’s new guidelines arrive to fill gaps, standardize methodologies, and demand a higher level of detail in registration and post-registration dossiers. The publication reinforces the agency’s commitment to ensuring that only medicines with robust quality profiles reach the consumer.
Below, we detail what the new guidelines require and how the industry should prepare for this regulatory update.
What the New Guidelines Require of the Industry
ANVISA’s new guidelines, formalized through Specific Guides or changes to Collegiate Board Resolutions (RDCs), align Brazil with the standards established by the International Council for Harmonization (ICH), particularly guidelines Q3A and Q3B, which address impurities in APIs and finished drug products.
- Stricter Classification and Acceptance Limits
The enhanced Guide establishes clear criteria for the classification of impurities:
Organic Impurities: Subdivided into API-related impurities (including degradation products), process-related impurities, and those introduced by excipients. The Guide requires the identification and quantification of all impurities present above a specific reporting threshold for the maximum daily dose.
Inorganic Impurities and Residual Solvents: Validated analytical methodologies are required for precise quantification, with strict limits based on toxicity.
Genotoxic Impurities: The guidelines demand a detailed toxicological risk assessment for these substances (which can damage DNA), with the application of the Threshold of Toxicological Concern (TTC) concept. Control in this area is extremely rigorous.
- The Forced Degradation Study
A central point of the new directives is the requirement for a more robust forced degradation study for degradation products.
Purpose: The manufacturer must subject the API and the finished product to extreme conditions (heat, humidity, light, acidic/basic pH, oxidation) to generate and identify all possible degradation products.
Regulatory Benefit: This step is crucial for the development and validation of analytical methods capable of separating and quantifying the API from its degradation products (stability-indicating methods), ensuring that the drug’s potency is correctly determined over time.
- Detail in Registration and Post-Registration Dossiers
The quality of information submitted to ANVISA is intensified:
It is mandatory to present the toxicological justification for unidentified impurities, or for identified impurities that exceed the standard acceptance limits.
The methodology for calculating acceptance limits and testing limits must be clear and transparent, demonstrating that the drug is safe throughout its entire shelf life.
Important Points: Preparation and Compliance for the GRP Brazil Industry
For pharmaceutical companies and importers, compliance with the new guidelines must be immediate:
Analytical Review: It is crucial to review all quality control and stability analytical methods. Methods must be revalidated to ensure they are sufficiently selective and sensitive to quantify impurities at the new established limits.
Up-to-Date Dossiers: Prioritize the updating of registration dossiers, especially those for older medicines, ensuring that impurity specifications comply with the new guidelines, avoiding ANVISA requirements (and delays).
Stability Management: Reinforce stability programs to monitor the formation of degradation products over time. In-depth knowledge of the drug’s degradation profile is mandatory.
Team Training: Invest in training R&D, Quality Control, and Regulatory Affairs teams on the ICH guidelines and ANVISA’s specific requirements, ensuring consistent application of the new limits.
Conclusion
The global regulatory landscape for AI/ML medical devices is undergoing a full transformation, seeking to balance the speed of technological innovation with the need to protect patient safety. The FDA’s TPLC model, with its emphasis on pre-specified change control, offers a promising path for managing adaptive algorithms.
For GRP Brazil, it is imperative that companies developing or importing AI/ML SaMD adopt a proactive regulatory strategy, focused not only on initial approval but also on post-market change management and bias mitigation. Regulatory compliance in this sector now requires expertise in software engineering and data science, in addition to traditional good manufacturing practices.
GRP Brazil
If you are interested in registering your products in Brazil, GRP is ready to help. Our team of experts can simplify the process of registering products in Brazil and make it easier to schedule meetings with Anvisa more efficiently.
GRP can act as your local Agent & Register your product in U.S
Contact our team today to Inquire!
Email: info@globalregulatorypartners.com
Telephone : (+1) 781-672-4200
References
Learn more about Anvisa.
About Global Regulatory Partners
Global Regulatory Partners Inc, (GRP) is an American company that provides regulatory affairs, clinical, quality and safety services to medical devices, pharmaceutical, cosmetic and Food Supplement companies globally.
GRP headquarters is located in Massachusetts USA and its main affiliates are located in China, Japan, Brazil, Mexico and South Korea. GRP helps many life science companies register their products in different countries in compliance with local regulations.