WHO Points to Consider on Continuous Manufacturing

The World Health Organization (WHO) has recently released draft guidelines on continuous manufacturing (CM) in the pharmaceutical industry, marking a significant step towards global harmonization of this innovative manufacturing approach. This guidance comes a few years after the International Council for Harmonisation’s (ICH) Q13 guideline, which was finalized in 2023. Let’s explore the main points of the WHO draft guidance and how it compares to ICH Q13.

Key Points of WHO Draft Guidance on Continuous Manufacturing

Risk Management

The document emphasizes the importance of robust risk management strategies in CM processes. Manufacturers are expected to identify, assess, and mitigate potential risks associated with the continuous nature of production.

Control Strategies

WHO outlines best practices for developing and implementing effective control strategies in CM. This includes real-time monitoring and control of critical process parameters and quality attributes.

Process Dynamics

The guidance addresses the unique challenges of managing process dynamics in continuous systems, including strategies for handling transient states and disturbances.

Validation of Computerized Systems

Given the heavy reliance on automation and digital systems in CM, the WHO document provides specific guidance on validating computerized systems used in continuous manufacturing processes.

Batch Definition and Traceability

The guidance offers recommendations on defining batches in a continuous process and ensuring traceability throughout the manufacturing chain.

Comparison with ICH Q13

While the WHO draft guidance and ICH Q13 share many common elements, there are some notable differences and complementary aspects:

Scope and Applicability

• ICH Q13: Applies to CM of drug substances and drug products for chemical entities and therapeutic proteins, including biosimilars.
• WHO Guidance: Likely to have a broader scope, covering even excipient manufacturing.

Regulatory Approach

• ICH Q13: Provides a harmonized approach for regulatory submissions and assessments across ICH member countries.
• WHO Guidance: Aims to provide a global framework that can be adopted by regulatory authorities worldwide, especially in countries not part of ICH.

Technical Detail

• ICH Q13: Offers in-depth technical guidance, including annexes for specific types of products and manufacturing scenarios.
• WHO Guidance: May provide more general principles and best practices that can be adapted to various regulatory and manufacturing contexts.

Implementation Focus

• ICH Q13: Emphasizes scientific and regulatory considerations for development, implementation, and lifecycle management of CM.
• WHO Guidance: Likely to include more practical considerations for implementing CM in diverse manufacturing environments, including resource-limited settings.

Implications for the Pharmaceutical Industry

The release of the WHO draft guidance on continuous manufacturing, following ICH Q13, signifies a growing global consensus on the importance and potential of CM in pharmaceutical production. This alignment between major global health organizations is expected to:

1. Accelerate the adoption of continuous manufacturing technologies worldwide.
2. Provide clearer pathways for regulatory approval of CM processes, especially in non-ICH countries.
3. Encourage innovation in pharmaceutical manufacturing, potentially leading to more efficient and flexible production of essential medicines.
4. Improve global supply chain resilience by enabling more localized and adaptable manufacturing capabilities.

As the pharmaceutical industry continues to evolve, the harmonization of guidance documents from WHO and ICH on continuous manufacturing will play a crucial role in shaping the future of drug production. Manufacturers, regulators, and other stakeholders should closely follow the finalization of these guidelines and prepare for a new era of pharmaceutical manufacturing that promises improved quality, efficiency, and accessibility of medicines worldwide.