Continuous manufacturing (CM) introduces the biggest transformation in pharma manufacturing in decades. The promise: lower cost, faster production, higher quality and speed to market. But CM is not just about new technology and manufacturing methods – it impacts the entire supply chain and forces a recalibration of supply strategies.
CM is not a new concept. In many industries continuous processing, a highly automated production concept integrating multiple chemical production steps, has become very common. The benefits that can be realized by switching from batch to continuous manufacturing are obvious. However, CM has not found broad application in pharma until now.
A new landscape of opportunities
Chemical pharma production has not changed much over the past 50 years. Due to high profitability and regulatory barriers for change, pharma organizations were not particularly keen on introducing changes to their existing production environments. Traditionally companies apply conventional batch approaches with separate process steps throughout the production – from blending raw materials to formulation and packaging of the final product – with quality checks at each stage. These operation methods meet regulatory requirements and work together effectively, but the breaks between the single steps cause inefficiencies and extend the overall processing time considerably – with an increasing risk of (mainly human) errors during the starts and stops.
In contrast, CM uses sensor technology and in-line analytics to measure the critical physical and chemical properties and processing conditions in real-time, steering the production process automatically. This allows for an uninterrupted flow across multiple production steps from raw materials to synthesis to final dosage form. With a series of compelling benefits:
15-30% reduction in production (i.e. conversion) cost
About 50-70% less manpower required due to automation
Considerably higher OEEs (75%+)
60-80% reduction in end-to-end batch lead time (i.e. time taken from raw material dispatch to finished product quality release)
50% reduction in product deviations
50-70% reduction in time needed for quality control (according to CM implementation at Pfizer and GSK). Up to 40% reduction in power consumption
50-70% smaller physical footprint of the equipment
Considerably faster scale up if CM is already applied in clinical trial stage
Considerably faster tech transfers since processes are fully automated
Many of these advantages also fit the agendas of regulators who are pushing for higher quality and reliability in manufacturing to ensure safety and affordability of drugs. The US Food and Drug Administration (FDA), for example, encourages pharma organizations to implement continuous manufacturing concepts and offers accelerated approval processes for that matter. Regulators in Europe and Japan are expected to follow.
Innovators in the game
A substantial landmark towards the integration of CM in pharma production was reached in April 2016: Johnson & Johnson had been working for several years to switch the production for its HIV drug Prezista for its Janssen plant in Puerto Rico from batch to continuous manufacturing. The regulatory approval from the FDA – the first of its kind – was a ground breaking achievement.
Companies like GEA offer modular, scalable and easy to integrate tools meeting all applicable process requirements. There is considerable partnering going on to increase ‘off the shelf’ readiness. These partnerships are being instigated by pharma companies, equipment vendors and technology companies, and even contract manufacturers.
A recent partnership between Siemens and GEA, for example, will bring an integrated continuous tablet manufacturing line to life. GlaxoSmithKline has teamed up with Pfizer, GEA and G-CON Manufacturing to design a next-generation portable, continuous, miniature and modular (PCMM) prototype for development, clinical trials and commercial manufacturing of oral solid dose forms. The production-on-demand (POD)-based mini factory has a 60 percent smaller footprint than conventional production facilities, can be shipped by truck to any location and has a setup time of less than a year. Regulatory approval for CM provided, using a PCMM solution, manufacturers can rapidly duplicate the POD and efficiently manufacture their product in the quantity needed close to the target market.
Overcoming existing legacy structures
In most cases the introduction of CM does not start on a green field. The biggest hurdles for the introduction of CM are existing – already written-off - legacy production facilities and the required regulatory efforts to switch existing products to CM in all affected target markets. With ongoing investments in digital technologies to incrementally optimize existing batch and semi-batch operations, a hybrid batch and CM strategy will most certainly lead the way into the CM era. However, CM is not a mere technical solution. It requires significant investments and forces pharma companies to assess the implications of CM on their supply strategies. New capabilities and skills must be developed, bought or acquired through partnerships. It takes the combination of production technology, process engineering and regulatory knowledge as well as experience in transforming manufacturing and supply operations to bring CM to life.
Thinking beyond the business case
For pharma, this is an exciting time. Though initial investments for the transition from batch to continuous manufacturing are high, CM is becoming a priority and many pharma organizations are currently exploring initiatives. Companies are convinced that CM is the future of pharma. Without a doubt, a solid understanding of the business case for individual CM initiatives and clearly planned and evaluated migration scenarios are vital. However, a transformation of that magnitude also requires strategic moves. Pharma companies need to act now to build the required long-term capabilities and partnerships to reap the benefits of more cost efficient, reliable and scalable operations.