DMS Insights from Cognidox

Quality by Design: How to embrace ICH Q8 R2 for pharma excellence

Written by Joe Byrne | 21 Mar, 2024

ICH Q8 R2 are international guidelines for ensuring Quality by Design in pharmaceutical development. Here’s why a QbD control strategy should be driving your company’s drug development process.

What are the ICH Q8, Q9, and Q10 guidelines? 

The ICH has developed tripartite guidelines for the quality and risk management of the pharmaceutical development and manufacturing process. These mutually supportive guidelines, ICH 8, ICH 9 and ICH 10, cover how pharma companies should:

  • Establish a QbD development process (Q8) 

What are the ICH Q8 R2 Guidelines? 

The ICH Q8 Pharmaceutical Development guidelines are a comprehensive framework for using QbD (Quality by Design) principles to ensure a systematic, process-driven approach to drug development.

What is Quality by Design (QbD)? 

QbD involves designing quality into the product through effective planning and management of each development and manufacturing stage. This marks a shift away from using a traditional, experimental approach to pharma development and QC testing. Instead, QbD looks to develop a more dynamic, comprehensive quality assurance (QA) methodology that ‘bakes quality’ into the product from its inception.

Is ICH Q8 mandatory for pharma developers?

ICH quality guidelines are not mandatory for developers but are increasingly being embraced to control the wasted time, resources and inconsistent results that have been endemic in the pharma space.

Why the industry needs the ICH’s QbD approach 

Research suggests ineffective and inconsistent quality management is increasing the overall cost of pharmaceutical development and fuelling escalating drug prices.

According to research published by the LSE in 2020, the median cost of bringing a new drug to market was estimated to be $985 million, while the average cost was $1.3 billion

(source LSE)

Testing failures, inefficiencies in preclinical experiments, issues with monitoring and maintaining manufacturing standards all contribute to high levels of abandoned projects, failed audits, and product recalls.

Indeed, in 2022, drug recalls reached a five-year high while the aggregated cost of quality failures in the global industry ran into billions.

What are the pillars of QbD in the ICH Q8 guidelines? 

The ICH Q8 guidelines help developers ensure they adequately define a product profile before they begin their development process. It asks them to identify a product’s critical quality attributes (CQAs) and then show how they will select raw materials, create SOPs and control Critical Process Parameters (CPPs) to deliver designs that consistently meet quality demands.

Linking and animating all these elements is the ‘control strategy’ - the combination of process and data-driven decision-making that results in validated drug designs and manufactured products that are safe and efficacious.

Here’s how these elements work together to ‘bake in’ quality to your end products from the start:

Quality Target Product Profile (QTPP)

 

  • The QTPP serves as the foundation for all drug design and development. It defines the intended use, target patient population, delivery route, dosage form, and other critical product characteristics.
  • Development teams use the QTPP to guide their formulation and process development, ensuring that all design and development efforts align with the desired quality objectives.
  • Early definition of the QTPP facilitates a targeted approach to development, allowing for the identification of relevant Critical Quality Attributes (CQAs) and the establishment of SOPs that can deliver required results.

Critical Quality Attributes (CQAs)

 

  • CQAs are identified based on their impact on product safety, efficacy, and quality, informed by the QTPP. This identification focuses development efforts on what is most critical to product quality.
  • Understanding the relationship between CQAs and process parameters enables the development of robust manufacturing processes that can consistently produce products meeting these quality attributes.
  • Monitoring and control of CQAs through analytical testing and in-process controls ensure the final product consistently meets quality standards.

Risk Management 

 

  • Systematic risk management is applied to identify potential product quality risks and prioritise these risks based on their impact and likelihood.
  • Risk assessments inform the design of experiments, process controls, and quality monitoring strategies, ensuring resources are allocated efficiently to areas of highest risk.
  • Ongoing risk management throughout the product lifecycle allows for the proactive identification and mitigation of emerging risks, ensuring continual quality improvement.

Design Space

 

  • A design space is created through a deep analysis of how various manufacturing conditions—such as temperature or mixing speed (process parameters) and the properties of materials used (material attributes)—impact the essential qualities of a pharmaceutical product (Critical Quality Attributes, or CQAs).
  • This analysis helps to map out a specific range of conditions, known as the design space, where adjustments can be safely made to the manufacturing process without compromising the product's quality.
  • Regulatory acceptance of a defined design space can reduce the need for regulatory submissions for process changes, encouraging innovation and continual improvement.

Control Strategy

 

  • A comprehensive control strategy is developed based on product and process understanding. This strategy encompasses material controls, process controls, and product specifications to ensure quality.
  • Implementation of the control strategy includes real-time monitoring of process parameters and controls to ensure operations remain within the design space.
  • The control strategy is supported by a robust quality management system and is continually assessed and updated based on process performance and product quality data, facilitating a state of control and continual improvement.

The vital role of documentation and digital control in QbD 

Documentation should inform and record every step of your process 

At the heart of QbD lies the documentation of every aspect of pharmaceutical development, from the definition of the Quality Target Product Profile (QTPP) to the regulatory submission of your proposed design space and the management of the design-to-manufacture process.

Documentation supports and evidences all your decision-making, creating records of approval, change control, deviation management, and process validation. It proves to regulators and auditors your product has been designed and manufactured exactly as you have specified - minimising the risk of failure in every part of the cycle.

Digital document control should ensure complete traceability 

But in a sector where developers generate so much complex data and documentation, it’s impossible to organise it all manually. You need to ensure that all the documents you create are being indexed and controlled as they are created - automatically generating the complete audit trails you need to share with regulators like the FDA.

The integration of digital technologies to control your process and documentation should help you derisk and accelerate every part of your drug development process, making each project more transparent and auditable.

Developers need digital tools to bring their control strategy to life 

The right  eQMS system will give you the tools to: 

  1. Store quality records and documents safely and prevent them from loss or fabrication.

  2. Ensure the integrity of data and documentation according to ALCOA principles.
  3. Create workflows to ensure design and quality documents are subject to required reviews and approvals.

  4. Create document holders to ensure required groups of documents can be collated and reviewed together by specific stakeholders - before the next stage of a process is triggered.

  5. Impose change controls to ensure key processes and documentation are never changed without permission.

  6. Deviation management - showing how you investigate non-conformances and trigger CAPA processes.

  7. Handle Process Analytical Technology (PAT) and advanced data analytics with mechanisms for real-time monitoring and control of manufacturing processes.

  8. Instigate automatic process review to fuel continual improvement efforts across your product development lifecycle.

Conclusion 

The ICH Q8 guidelines have been pivotal in promoting the Quality by Design approach within the pharmaceutical industry. As companies increasingly adopt these principles, we can expect a future where drug development is not just about meeting regulatory standards but about exceeding them.

For scaling drug development companies, the challenge is finding the QMS tools that can help them marshal and automate their process and documentation - without imprisoning them within the expensive and inflexible software packages deployed by the pharma giants.