Moving from batch to continuous processing may not seem like a major issue, but that’s not the case in the pharmaceutical and biotechnology industry. Continuous processing works fine in most high-volume industries with well-known processes. But pharma is a highly regulated, largely batch-oriented industry that does not regularly lend itself to continuous processes. That said, the use of novel science and technologies for continuous manufacturing can also lead to innovative pharma and biotech products and help pharma companies resolve some long-standing cost, quality inspection and supply-chain issues.
Well over a decade ago, the pharma and biotech industry started looking at producing products in continuous processes, rather than in batches. While most industry participants agreed that for high-volume, high-demand specialty drugs produced chemically in batches, the move from batch to continuous processing could work well. However, this doesn’t necessarily apply to biologics, which have very specific requirements.
Regulatory Approvals
Earlier this year, the European Medicines Agency and the US Food & Drug Administration (FDA) gave their approvals to Janssen Pharma and Novartis, respectively, to manufacture certain products in continuous processes. Janssen, a division of Johnson & Johnson, received FDA’s first approval to produce a drug to treat HIV (Prezista) in April 2016. Novartis is working with the Massachusetts Institute of Technology (MIT) to build a GMP continuous manufacturing facility. In most cases, rather than a fully continuous process, most of these examples involve a hybrid approach in either manufacturing or separation. Regardless, this is clearly a step in the right direction in terms of pharmaceutical innovation.
At the same time, Vertex Pharmaceuticals, working in conjunction with CDMO, Hovione, is building a commercial-scale facility in New Jersey to produce a cystic fibrosis drug continuously. The plant is due for completion in 2018. This facility will also be used for contract manufacturing and include continuous blending, wet and dry granulation and fluid bed drying, tableting and coating operations. Other companies, including GlaxoSmithKline (GSK) and Amgen, are working on methods for continuous production.
In the US, FDA is collaborating with academia and industry to assess how new manufacturing technologies may affect product safety, efficacy and quality. The resulting information is critical to inform FDA as it develops associated regulatory policy. This project is intended to investigate whether a shift from batch to continuous manufacturing would negatively impact product quality.
Why Move from Batch to Continuous Processing?
While relatively time consuming and costly, the well-established method of producing drugs in batches is still viable for smaller, specialized and customized drugs. But for high-demand, high-volume drugs, it often makes sense to produce them continuously - and not just for economic reasons. The regulatory agencies seem to be open to the idea that continuous production could reduce some persistent quality problems and help eliminate drug shortages.
The cost savings for manufacturers relate to both space and time. Compared to batch processing, continuous processing lines typically require less space and significantly less time to produce a given amount of on-spec product. ARC has seen estimates for cost reductions as high as 30 percent.
The benefits for switching from batch to continuous processes include:
• Smaller facilities needed to manufacture a given amount of product
• Production times reduced from four to six weeks, to just hours
• Increased automation reduces human errors and can improve regulatory compliance
• Improved ability to meet market demands
• Reduced waste and environmental impact
• Reduced costs
Not surprisingly, leading pharmaceutical manufacturers are jumping on this bandwagon. According to an article in the Wall Street Journal, Johnson & Johnson wants to manufacture 70 percent of its high-volume products on continuous processing lines within eight years. Amgen already uses continuous manufacturing processes at its Singapore plant and GSK has built a $29 million continuous manufacturing plant in Singapore. Most of the projects underway are for the processing finished products from active pharmaceutical ingredients (API).
Regulatory Agencies Now “On-Board”
While the pharmaceutical industry has been slow to adopt approaches embraced by other industries, regulatory agency requirements can no longer be blamed. In September 2017, the FDA issued draft guidance to help pharmaceutical manufacturers implement various technological advances and we’re seeing similar activity by the European regulatory agencies. Industry insiders believe this guidance helped Janssen receive the first approval to switch from batch to continuous processing for its HIV-1 treatment, Prezista (darunavir). The company can now produce 600 mg tablets on a continuous line in Puerto Rico, which integrates weighing, milling, blending and compression.
FDA is encouraging manufacturers to be more innovative and thus can no longer be held responsible for limiting pharma manufacturing production. The pharmaceutical industry is starting to respond to a changing and demanding marketplace. While slow to gain traction initially, the amount of research activity and partnerships in the industry for continuous manufacturing seem to indicate a faster changeover to continuous than originally anticipated.
As a result, ARC believes that both manufacturing and manufacturing-related automation will become more strategic to the pharmaceutical industry in the future.
Many pharmaceutical manufacturers could realize significant benefits by switching from batch to continuous manufacturing, particularly for high-volume, non-biologic products. This will require implementing new processes, new digital solutions, and advanced automation technologies. If you have not already started investigating these types of manufacturing approaches and technology solutions, ARC recommends that you put it on your agenda, and soon.
