ASTM E2968-23 PDF

Overview

ASTM E2968-23, titled Standard Guide for Application of Continuous Manufacturing (CM) in the Pharmaceutical Industry, provides a comprehensive framework for the implementation and operation of continuous manufacturing technologies for pharmaceutical products. This ASTM guide supports manufacturers in selecting, developing, and operating CM systems, emphasizing the engineering and scientific principles that set CM apart from traditional batch processing. Designed primarily for non-biopharmaceutical applications, the standard can be applied to both drug substance (DS) and drug product (DP) manufacturing. ASTM E2968-23 addresses process dynamics, control strategies, and quality management, while recognizing regulatory expectations and industry best practices.

Key Topics

• Continuous Manufacturing Definition: The standard describes CM as an integrated process where raw materials are continuously introduced and transformed through a series of interconnected operations, with finished products removed on an ongoing basis.
• Process Dynamics & Control: It highlights the significance of understanding process dynamics (such as residence time and residence time distribution), process control strategies (feedback, feedforward, multivariate control), and how they impact product quality.
• Integration & Process Flow: The guide contrasts isolated continuous unit operations with the greater potential benefits of fully integrated CM lines.
• Operational Considerations: Key guidance is provided on lifecycle management of CM systems, from development and scale-up to long-term operation and discontinuation.
• Material Properties: Emphasizes early assessment of material properties-especially for solid dosage forms-to design reliable flow and transport systems, reducing risks of segregation, attrition, or process failure.
• Process Robustness: Offers recommendations for robust process design, ongoing risk analysis, and strategies to manage process disturbances, material variability, and equipment wear.
• Regulatory Alignment: Aligns with international guidance, recognizing requirements from FDA, ICH, EMA, and Good Manufacturing Practices (GMP).
• Limits of Standard: The guide does not cover every aspect (e.g., it does not dictate equipment safety practices or prescribe specific process designs). Users are responsible for applying relevant safety, health, and regulatory controls.

Applications

• Pharmaceutical Manufacturing Optimization: The standard assists pharmaceutical companies implementing continuous manufacturing technologies to increase efficiency, improve product quality, and reduce production time.
• Process Development: Applies to the design of new manufacturing processes or retrofit/redesign of existing batch processes, supporting innovation and modernization efforts.
• Quality Control and Risk Management: Proposes a science-based, risk-oriented approach to process development, emphasizing continuous monitoring and robust control strategies to ensure product quality.
• Regulatory Compliance: Supports manufacturers in meeting regulatory expectations for process validation, traceability, and change management in continuous manufacturing operations.
• Scale-up and Commercial Production: Provides principles for scaling-up continuous manufacturing processes from development to full-scale commercial production, taking into account process robustness and material traceability.
• Troubleshooting and Root Cause Analysis: Offers tools for understanding disruptions in continuous production, optimizing corrective actions, and minimizing the impact on product quality.

Related Standards

• ASTM E2363: Terminology Relating to Process Analytical Technology in the Pharmaceutical Industry
• ASTM E2475: Guide for Process Understanding Related to Pharmaceutical Manufacture and Control
• ASTM E2537: Guide for Application of Continuous Process Verification to Pharmaceutical and Biopharmaceutical Manufacturing
• ASTM E2629: Guide for Verification of Process Analytical Technology (PAT) Enabled Control Systems
• ASTM E2898: Guide for Risk-Based Validation of Analytical Methods for PAT Applications
• FDA Guidance for Industry – PAT: A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance
• ICH Q8, Q9, Q10, Q11, Q13: International guidelines on pharmaceutical development, quality risk management, quality systems, and continuous manufacturing
• EMA/EU GMP guidelines: Process validation and qualification for pharmaceutical manufacturing

By adopting ASTM E2968-23, organizations can confidently advance pharmaceutical continuous manufacturing with clear, internationally recognized guidance, supporting both regulatory compliance and operational excellence.