Using ValGenesis iRisk for Better CMC Process Development


Quality by Design (QbD) is a cornerstone of modern pharmaceutical process development. As a framework, QbD emphasizes a systematic and proactive approach to ensuring that pharmaceutical products meet predefined quality criteria.

The QbD framework is also endorsed by the International Council for Harmonization (ICH) through guidelines such as ICH Q8 (R2) and ICH Q9 (R1)

Central to QbD is the identification of critical quality attributes (CQAs) and the establishment of control strategies to manage these attributes throughout the manufacturing process. 

In this blog post, we’ll explore how ValGenesis iRisk is the ideal tool to facilitate the application of QbD frameworks, providing a robust platform for methodical risk assessments and quality management throughout the product lifecycle.


Why is Quality by Design so Important? 

Quality by Design acquired its importance in pharmaceutical process development for several reasons, such as: 

Enhanced Product Quality and Consistency 

The QbD framework emphasizes understanding and controlling variability in manufacturing processes, ensuring that the final product consistently meets predefined quality criteria. This approach leads to more reliable and high-quality pharmaceutical products.

Regulatory Compliance 

Regulatory agencies like the FDA and EMA strongly advocate  QbD principles. Applying the QbD framework facilitates regulatory submissions, as it demonstrates a thorough understanding of the process and product, potentially accelerating approval timelines and reducing the likelihood of regulatory hurdles.

Risk Management

Quality by Design incorporates risk management strategies to identify, assess, and mitigate risks throughout the product lifecycle. By systematically evaluating potential risks and implementing control measures, companies can prevent issues before they arise, ensuring patient safety and product efficacy. 

Efficiency and Cost-Effectiveness 

Implementing QbD can lead to more efficient processes, reducing the need for extensive end-product testing and rework. This efficiency translates to cost savings in production and reduced time to market for new drugs. 

Scientific Understanding and Process Knowledge

The QbD approach requires a deep understanding of the product and process, including CQAs and critical process parameters (CPPs). This knowledge enables better decision-making, robust process design, and continuous improvement.

Robust Control Strategies 

By identifying CQAs and CPPs, QbD helps in developing robust control strategies that ensure product quality. These strategies are based on scientific data and risk assessments, leading to more reliable and predictable manufacturing outcomes.

Flexibility and Innovation 

A focus on QbD promotes a flexible regulatory framework where changes in the manufacturing process can be managed through a well-understood design space. This flexibility encourages innovation and continuous improvement, allowing companies to adapt to new technologies and methodologies.

Knowledge Management 

Quality by Design emphasizes comprehensive documentation and knowledge sharing; this ensures valuable information is not lost over time and can be reused in future projects, enhancing efficiency and fostering a culture of continuous improvement.

Patient Safety

Ultimately, the primary goal of QbD is to ensure patient safety by delivering high-quality pharmaceutical products. By systematically designing quality into the manufacturing process, QbD minimizes the risk of product recalls and adverse effects, safeguarding public health.


What About Analytical Quality by Design? 

Analytical Quality by Design (AQbD) is an extension of the QbD principles specifically applied to the development of analytical methods.  

Just as QbD enhances pharmaceutical process development, AQbD brings significant advantages to the development and validation of analytical methods, ensuring the methods are robust, reliable, and capable of consistently delivering accurate results. The ICH also endorses AQbD through its Q14 guidelines. 

Similarly to QbD, it features several benefits such as:

Systematic Method Development 

Analytical Quality by Design takes a structured approach to method development, starting with a clear understanding of the analytical target profile (ATP) and the critical method attributes (CMAs). This ensures the development process is thorough and systematic, leading to robust methods.

Improved Method Robustness and Reliability

By identifying and controlling critical method parameters (CMPs) and their impact on method performance, AQbD enhances the robustness and reliability of analytical methods. This means the methods are less susceptible to variability and can consistently produce accurate and precise results.

Enhanced Method Understanding

Analytical Quality by Design involves a deep understanding of the analytical method and its performance characteristics. This knowledge helps scientists identify potential sources of variability and implement strategies to control them. It also aids in troubleshooting and continuous improvement of the method. 

Regulatory Compliance and Flexibility 

Regulatory agencies increasingly expect the application of QbD principles in analytical method development; AQbD facilitates smoother regulatory submissions by demonstrating a thorough understanding of the method and its robustness. Additionally, AQbD allows for greater regulatory flexibility, enabling method changes within the defined method operable design region (MODR) without the need for revalidation.

Lifecycle Management 

The AQbD framework supports the entire analytical method lifecycle, from development through validation to routine use. By continuously monitoring and improving the method based on performance data, AQbD ensures sustained method performance and reliability.

Data-Driven Decision-Making 

Analytical Quality by Design relies on statistical and risk-based approaches to make informed decisions during method development. This data-driven approach enhances the quality and reliability of the method, providing a solid foundation for making method-related decisions.

Facilitated Knowledge Transfer 

The AQbD framework promotes comprehensive documentation and knowledge sharing. This facilitates the transfer of method knowledge within and between organizations, ensuring consistency and continuity in method application and improvement.


How ValGenesis iRisk Supports the Application of QbD Frameworks 

ValGenesis iRisk is designed to integrate QbD principles and risk management practices seamlessly into the pharmaceutical development process. Here's how:

  1. Early-Stage Development: Quality Target Product Profile (QTPP) and CQAs 
    At the outset, iRisk enables teams to define the Quality Target Product Profile (QTPP) and identify critical quality attributes (CQAs). Each attribute is evaluated against various criteria, considering its impact and uncertainty. This systematic evaluation ensures that all critical aspects of the product are identified and prioritized from the beginning.

  2. Process Mapping and Parameter Criticality
    iRisk facilitates detailed process mapping, allowing teams to document every step and its associated process parameters. By correlating CQAs with specific process parameters, iRisk helps establish a correlation matrix. This matrix assesses how each parameter impacts the quality attributes, aiding in the determination of their criticality. The rationale behind decisions is documented, promoting transparency and easy access to critical information.

  3. Seamless Transition from Early-Stage to Late-Stage Development
    As development progresses, iRisk ensures that risk assessments are seamlessly transferred from early to late stages. This continuity prevents information loss and rework, allowing teams to build upon existing knowledge. During late-stage development, tools like FMEA (Failure Modes and Effects Analysis) come into play, helping prioritize critical risks and develop mitigation strategies.

  4. Automated Control Strategy and Reporting 
    iRisk's capabilities extend to the automated development of control strategies based on risk assessments. This automation accelerates the creation of robust control strategies essential for maintaining product quality. Real-time reporting features within the platform empower prompt collection and analysis of data, enhancing decision-making and regulatory compliance.

  5. Knowledge Management and Reuse
    One of the standout features of iRisk is its ability to facilitate knowledge management. Information from past projects, similar products, or different dosages can be reused with a single click, reducing the need to start assessments from scratch. This not only saves time but also promotes consistency and continuity across projects. 


Why is ValGenesis iRisk a Much Better Tool for QbD than Spreadsheets? 

Using a specialized platform for QbD implementation in pharmaceutical process development offers numerous advantages over traditional spreadsheet-based methods. 

With ValGenesis iRisk, pharmaceutical companies can ensure greater efficiency, improved data integrity, and better regulatory compliance, ultimately leading to higher quality and more reliable products. 

ValGenesis iRisk features the following capabilities: 

  1. Single Repository 
    ValGenesis iRisk provides a single repository for all data related to the QbD process. This ensures that all relevant information is stored in one place, making it easily accessible and reducing the risk of data fragmentation. In contrast, spreadsheets are often scattered across disparate systems and physical locations, leading to potential data loss and inconsistencies.

  2. Seamless Data Transition
    In ValGenesis iRisk, data moves easily from the early to late stages of development, maintaining continuity and ensuring that all stakeholders have access to the latest information. Spreadsheets require manual updates and transfers, increasing the risk of errors and data loss during transitions.

  3. Smart Detection of Areas of Concern 
    ValGenesis iRisk comes with built-in intelligence to detect areas of concern automatically. It can flag potential issues based on predefined criteria and historical data, enabling proactive risk management. Spreadsheets lack this level of automation and require manual monitoring, which is time-consuming and prone to human error.

  4. Collaborative Environment
    ValGenesis iRisk facilitates a collaborative environment where multiple stakeholders can access and contribute to the same data in real time. This enhances communication and ensures that everyone is on the same page. Even when shared, spreadsheets do not offer the same level of real-time collaboration and version control.

  5. One-Click Reporting 
    ValGenesis iRisk offers robust reporting capabilities that allow users to generate comprehensive reports with a single click. This includes real-time data visualization and automated report generation. Spreadsheets require manual data compilation and report creation, which is labor-intensive and inefficient.

  6. Facilitated Knowledge Transfer
    ValGenesis iRisk ensures that knowledge and data from previous projects are preserved and easily transferable to new projects. This reduces redundancy and accelerates the development process. On the other hand, spreadsheets often require manual consolidation of historical data, which can be cumbersome and incomplete.

  7. Reusability of Assessments
    With ValGenesis iRisk, there's no need to start assessments from scratch. Previous assessments can be reused and adapted for new projects, saving time and resources. Spreadsheets do not inherently support this level of reusability and require manual effort to adapt existing data for new purposes.

  8. Audit Trail and Regulatory Compliance 
    ValGenesis iRisk provides a comprehensive audit trail and is designed to comply with regulations such as 21 CFR Part 11.  All changes are tracked and data integrity is maintained, which is crucial for regulatory compliance. Spreadsheets lack built-in audit trails and often do not meet regulatory requirements without extensive manual documentation and validation. 

Four Key Benefits of ValGenesis iRisk in Pharmaceutical Process 

While iRisk offers a multitude of advantages for applying QbD frameworks, four key benefits stand out: 

  1. Enhanced Regulatory Compliance
    By thoroughly understanding and documenting product and process risks, ValGenesis iRisk helps streamline regulatory submissions, reducing hurdles and expediting approval timelines.
  2. Accelerated Development Timelines
    The platform optimizes experimental design and risk assessment processes, leading to faster development of robust control strategies.

  3. Improved Knowledge Sharing 
    Centralized storage of quality risk management information reduces knowledge loss and fosters a collaborative environment for diverse and dispersed teams.

  4. Streamlined Knowledge Transfer 
    With iRisk, transitioning knowledge between stages or projects becomes effortless, ensuring continuity and efficiency.


ValGenesis iRisk stands out as a comprehensive tool that integrates QbD principles and robust risk management into pharmaceutical and biopharmaceutical process development and analytical method development.  

By providing a centralized, dynamic platform for risk assessments and quality risk management, iRisk enhances regulatory compliance, accelerates development timelines, and promotes effective knowledge sharing for pharmaceutical companies committed to delivering high-quality products.  

If you would like to know more about ValGenesis iRisk, reach out to our team of experts. 

The opinions, information and conclusions contained within this blog should not be construed as conclusive fact, ValGenesis offering advice, nor as an indication of future results.