Currently, the pharmaceutical industry has consistently employed a “batch production” approach. In the United States, batch production has played a significant role in the discovery, research, development, and manufacturing of new and innovative drugs. However, over time, many have come to recognize that batch production is not necessarily the most efficient manufacturing method nor the optimal approach to ensuring product quality. Furthermore, as production technologies advance, the pharmaceutical industry has begun exploring the replacement of batch production with continuous manufacturing.

Continuous manufacturing (CM) refers to 24-hour uninterrupted production. As a newer technology compared to batch production, it genuinely enhances the reliability and efficiency of drug manufacturing processes. In certain scenarios, processes that take a month to complete using batch production may require only days with continuous manufacturing. The benefits of continuous manufacturing for patients and the pharmaceutical industry are substantial, not only reducing production time but also enhancing efficiency. It minimizes production failures through more flexible testing and control measures, thereby preventing drug shortages. Continuous manufacturing can be applied to the entire production process or only to specific operations within it, allowing manufacturers to customize the approach based on product and business requirements.

As a global leader in drug regulation, the FDA has been a strong advocate for continuous manufacturing processes. As early as 2017, the FDA issued a draft guidance on Continuous Manufacturing (CM). In 2018, the FDA provided nearly $6 million in funding to three continuous manufacturing projects, aiming to help implement innovative technologies to improve product quality and modernize the industry. On February 26, 2019, the FDA issued the draft guidance document “Quality Considerations for Continuous Manufacturing,” which will significantly advance this technology. This 27-page guidance addresses CM-related issues across six sections: Introduction, Background, Quality Considerations, Information Placement in Regulatory Submissions, Definitions, and References. The third section, Quality Considerations, is the core focus of the entire guidance. It provides detailed coverage across seven key chapters: fundamental concepts of continuous manufacturing, control strategies, process validation, additional considerations for pharmaceutical quality systems, process scale-up, stability requirements, existing batch management, and bridging procedures for continuous manufacturing.

Continuous manufacturing and other emerging technologies offer significant advantages in increasing production capacity per unit volume, providing new avenues for optimizing capacity management and cost control. Less than four years ago, only one approved product utilized a continuous manufacturing process. Today, five approved products from four companies employ continuous manufacturing to treat conditions including cystic fibrosis, HIV-1 infection, breast cancer, and leukemia. Additionally, approximately 20 companies (including both brand-name and generic drug manufacturers) are collaborating with the FDA to develop and implement continuous manufacturing processes.

Achieving continuous manufacturing hinges on equipment, making it a hot research area for major domestic and international equipment manufacturers. Shanghai Milang has consistently dedicated itself to the R&D and manufacturing of automated intelligent pharmaceutical equipment, investing heavily in continuous manufacturing research in recent years. In 2018, Shanghai Mirang achieved breakthrough progress in pharmaceutical material handling (unpacking and weighing/dosing), successfully developing an automated unpacking and weighing/dosing production line. This innovation completely replaces traditional manual unpacking and weighing/dosing methods, enabling fully automated material handling. The line has been delivered to customers for use. As the world's first automated unpacking and weighing/dosing production line, it fills a gap in both domestic and international markets. This line can be applied to continuous production, enabling continuous material handling.

Shanghai Mirang recently organized technical personnel to discuss and study the FDA's draft guidance on continuous manufacturing. The draft has also been translated and is available for download at /shmirancom/htmledit/attached/file/20190528/20190528174116371637.docx. We welcome colleagues to download, discuss, and provide feedback.