As scientists continue to elucidate the genomic basis of diseases such as cancer, it is becoming increasingly possible to develop different drugs for the same condition and target patients with a specific genetic profile.
Not only will this result in the production of personalized therapeutics that will be required in smaller volumes, the manufacturing technologies involved will need to be more flexible and able to switch between producing different formulations and specialty products. The ultimate aim is to get safer medicines to market in a more efficient and cost-effective way, and make them locally, so that everyone has access to the most efficacious pharmaceuticals, wherever they are in the world.
The benefits of continuous manufacturing
Supported by the US Food and Drug Administration (FDA) and prompted by the agency’s Pharmaceutical Quality for the 21st Century program, producers and suppliers of oral solid dosage (OSD) forms have been encouraged in recent years to adopt continuous manufacturing (CM) technologies to modernize their production infrastructure.
The initiative promoted the use of CM technologies and inline process analytical technologies (PAT) that meet requirements for moving the concepts and practicalities of building quality by design (QbD) into the complete product lifecycle, from R&D through to manufacturing.
Many industries that process raw materials into finished products have largely abandoned batch processing in favor of more agile and efficient CM technologies that exploit fully integrated, all-in-one platforms. These closed, state-of-the-art systems enable an entire manufacturing process to be completed, from start to finish, without the need for stoppage. Effectively, raw materials are fed into the continuous processing line at one end and final product comes out the other. There is no inter-batch transfer from one processing stage to the next, and quality testing is done automatically and continuously at every stage using in-built analytical technologies.
A single CM line can be used to process any volume of product, from small quantities for formulation development and design of experiments (DoE), through to clinical trials and full-scale manufacture of new chemical entities and high volume generics. Product output is rapid, and volume can be adjusted according to need, such as in the event of major disease outbreaks, without the need for investment in costly new equipment or dedicated plant.
The food, fine chemicals, oil and gas industries have, during the last decade, demonstrated the ability of CM to improve efficiency and flexibility, while also increasing product quality and reducing costs. In more recent years, regulatory pressure and changing approaches to drug development have spurred the pharmaceutical industry to look outside its batch processing box. At the same time, process intensification, PAT-compatible inline monitoring and the implementation of QbD in the pharmaceutical industry have led to the development of smaller and more compact equipment. With the goal of achieving more consistent process control and, ultimately, higher quality and more patient-centric end products, manufacturers are increasingly moving away from batch-based systems and switching to CM.
Spearheading continuous manufacturing for tablets
With decades of experience in batch processing technologies and engineering, GEA has for the last 10 years pioneered the development of state-of-the-art CM technologies and solutions to produce OSD pharmaceutical formulations. Our highly versatile ConsiGmaTM manufacturing platform combines multiple technologies that convert powdered raw materials into coated finished drug products in one single, closed unit. ConsiGmaTM technology has been shown to enable faster, more consistent and reliable tablet production with the reduced use of resources and raw materials, less stoppage time and minimal manual intervention. Furthermore, whereas some batch-based operations take weeks to produce tablets, in some situations a continuous system can manufacture the same products within minutes.
CM platforms take up 70% less space than batch plants, so can be built more quickly and with much lower capital expenditure. Individual ConsiGmaTM units can be designed, deployed and approved for commercial-scale manufacture within a year, compared with 2–3 years for traditional plants. The ability to establish smaller, cost-effective and resource-efficient plants increases the chance that local manufacturing sites can be established to meet regional needs and so reduce global transport requirements. GEA now has more than 47 full continuous OSD manufacturing installations operational worldwide.
It is thanks to GEA’s ConsiGmaTM technology that, in 2015, Vertex Pharmaceuticals became the first pharmaceutical company to receive FDA approval for a therapeutic that was both developed and commercially manufactured using a CM platform. And GEA’s miniaturized, mobile ConsiGmaTM 25 unit forms the basis of a groundbreaking, award-winning collaboration between Pfizer, G-CON, GEA and, more recently, GSK, to develop the next generation of Portable, Continuous, Miniature and Modular (PCMM) solutions for pharmaceutical production. These on-demand mini-factories can be set up to manufacture medicines, at any production scale, just about anywhere in the world where basic utilities are available. Once production is no longer needed, they can be dismantled, transported and relocated elsewhere.
In 2011 the FDA’s Dr Janet Woodcock, Director, Center for Drug Evaluation & Research, stated: “Manufacturing experts from the 1950s would easily recognize the pharmaceutical manufacturing processes of today.” Just a few years on, continued innovation in manufacturing technologies and engineering by the industrial processing sector, combined with the pharmaceutical industry’s unwavering commitment to adopt faster and more agile processing technologies, is leading to rapid modernization. The upshot will surely be safer, cheaper and more accessible drugs for the whole world.
GEA’s H. McCoy Knight, VP North America, APC Pharma, notes: “Using a QbD approach, drug manufacturing cycle times — from API to product release — can now be measured in hours rather than weeks. The clear benefits demonstrated by the use of ConsiGmaTM technology are facilitating the switch to continuous manufacturing and helping the pharmaceutical industry to produce higher quality products, enhance drug safety, reduce its industrial footprint and decrease waste, which provides significant advantages to governments, companies and patients alike.