Risk Analysis and Impurities: Technical Intelligence for Reliable Decisions

In pharmaceutical analytical laboratories — whether in Research & Development or Quality Control — risk and impurity assessment is no longer a one-off regulatory requirement. Today, it’s a core part of technical strategy, patient safety, and the robustness of generated data.

At BizaLumière, we provide technical and scientific support to conduct these analyses with depth, solid foundation, and real-world applicability.

What’s at stake?

Impurities are not just numbers in a specification. They can compromise:

• The efficacy of the drug

• Patient safety

• Regulatory approval

• The company’s reputation

That’s why every impurity — whether elemental, residual, process-related, or degradation-derived — must be understood, classified, and controlled based on technical and toxicological risk.

⚠️ What Is Risk Assessment in the Pharmaceutical and Chemical Industry?

Risk assessment is a systematic process that identifies, analyzes, and evaluates potential issues that may compromise the quality, safety, efficacy, and regulatory compliance of pharmaceutical and chemical products.

It is an essential part of a robust Quality Management System, applied from development through commercialization.

Guidelines and Regulatory Standards

This practice is supported by international and national standards that guide its implementation:

• ICH Q9(R1) – Quality Risk Management
  A core document that defines principles and tools for managing quality risks. Widely adopted by agencies such as EMA, FDA, and ANVISA, its revised version reinforces the importance of risk-based decision-making.

• ANVISA – Guide No. 62/2023
  Adopts ICH Q9 principles and adapts them to the Brazilian context, detailing steps such as risk identification, analysis, evaluation, control, and communication.

• FDA – Quality Systems Approach to Pharmaceutical CGMP Regulations
  Emphasizes risk assessment as a tool to ensure compliance with Current Good Manufacturing Practices (CGMP).

• USP <1060> and <1092>
  Address risk aspects in analytical processes and impurity control.

Practical Applications

Risk assessment is used across various areas:

• Analytical Development and Validation
  Identifies critical variables that may impact method reliability.

• Impurity and Nitrosamine Control
  Assesses the likelihood of formation and toxicological impact of impurities, guiding preventive actions.

• Deviation Management, CAPA, and Equipment Qualification
  Prioritizes corrective actions based on severity and likelihood of occurrence.

• Pharmacovigilance and Benefit-Risk Assessment
  Continuously evaluates the safety profile of medicines post-marketing, as required by guidelines like ICH E2C(R2) and RDC No. 406/2020.

Benefits

• Evidence-based decision-making

• Focus on failure prevention and mitigation

• Greater regulatory and operational efficiency

• Strengthening of quality and safety culture

How We Work at BizaLumière

We provide technical support for:

• Nitrosamine Risk Assessment
  Evaluation based on chemical structure, manufacturing process, and formation potential.

• Elemental Impurities Risk Assessment
  Classification according to ICH Q3D, PDE calculation, and control strategies.

• Extractables and Leachables Risk Assessment
  Risk evaluation through packaging interaction, based on literature and simulated studies.

• Degradation Products and Related Impurities Risk Assessment
  Interpretation of stability and forced degradation studies, focusing on safety and compliance.

• Process Impurities and Synthetic Intermediates Risk Assessment
  Identification, justification, and proposal of technical control strategies.

All of this is grounded in scientific literature, regulatory guidelines (ICH, ANVISA, EMA), and technical reasoning tailored to laboratory reality.

What We Deliver

• Technical and toxicological impurity assessment (via specialized partner)

• Interpretation of stability and degradation studies

• Scientific research in regulatory and academic databases

• Proposal of control and mitigation strategies

• Technical reports with clear and applicable language

Types of Risk Assessment

Nitrosamines

• Technical Approach: Structural assessment and formation potential

• Regulatory Basis: EMA, ANVISA, ICH M7

Elemental Impurities (Metals)

• Technical Approach: PDE calculation and class-based categorization

• Regulatory Basis: ICH Q3D

Extractables and Leachables

• Technical Approach: Migration simulations and compatibility studies

• Regulatory Basis: USP <1663>, <1664>

Degradation Products

• Technical Approach: Stability interpretation and forced degradation studies

• Regulatory Basis: ICH Q1A, Q3B

Process Impurities

• Technical Approach: Technical justification and analytical control

• Regulatory Basis: ICH Q3A, Q3C

Problem Categorization Matrix: Clarity for Action

To conduct analyses with focus and precision, we use a technical matrix that classifies problems by origin, impact, and approach:

Process Impurities

• Examples: By-products, residual reagents

• Likely Origin: Synthesis and purification steps

• Impact: High

• Expected Treatment: Technical justification and analytical control

Elemental Impurities

• Examples: Heavy metals, catalysts

• Likely Origin: Raw materials, excipients, water

• Impact: High

• Expected Treatment: Toxicological evaluation and PDE calculation

Degradation Products

• Examples: Resulting from stability, oxidation, hydrolysis

• Likely Origin: Stability conditions and packaging type

• Impact: High

• Expected Treatment: Stability studies and specification review

Genotoxic Impurities

• Examples: Chemical structures with structural alerts

• Likely Origin: Manufacturing process and packaging

• Impact: Critical

• Expected Treatment: Evaluation according to ICH M7 and analytical control

Extractables and Leachables

• Examples: Migrated compounds from packaging

• Likely Origin: Materials in contact with the product

• Impact: High

• Expected Treatment: Simulated studies and compatibility review

This matrix allows investigations to be conducted with focus, agility, and depth — without compromising technical rigor.

Why Choose BizaLumière?

Because here, you’ll find technical consulting with scientific depth.

• 🔬 Technical consulting grounded in scientific expertise

• 🧪 Focused on practical application and laboratory routine

• 🚫 No audits — just real technical support

• 🎯 Personalized service, straight to the point

We don’t offer audits — we offer real support for those at the bench, facing complex decisions and seeking safe, well-founded solutions. We work with professionals who need clear answers, reliable decisions, and solutions that work in practice.

Need Technical Support for Risk and Impurity Assessment?

BizaLumière is ready to help. We provide technical and scientific support for:

• Complex analytical investigations

• Toxicological and regulatory risk assessments

• Interpretation of stability and impurity studies

• Proposal of practical, evidence-based solutions

Get in touch with BizaLumière and discover how to turn analytical complexity into clear, safe, and reliable decisions.

📧 contato@bizalumiere.com.br
🌐 www.bizalumiere.com.br

BizaLumière’s Process Flowchart

[1] Problem Identification
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[2] Technical Scenario Analysis
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[3] Scientific and Regulatory Research
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[4] Risk and Impact Assessment
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[5] Proposal of Practical Solution
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[6] Delivery of Technical Report