The Changing Face of Pharma Technology
Continuous Processing / Flow Chemistry
Continued growing interest in continuous processing reflects expectations that technological innovation can benefit operations across the board.
Pharma and biopharma manufacturers are seeking ways of increasing efficiency and productivity to reduce costs and time to market while at a minimum maintaining current product quality levels. Continuous processing for the production of both small- and large-molecule drugs offers the potential to increase efficiencies and product quality/consistency, while also reducing the manufacturing and environmental footprints and overall costs of operations.
While this potential has not yet been confirmed in many cases, most large and many small pharma/biopharma companies and contract manufacturing organisations (CMOs) have invested in continuous manufacturing equipment and technology to investigate its potential benefits.
A Pharmaceutical and Biotechnology Outsourcing Survey of more than 2,300 outsourcing-facing pharma and biotech executives consider technological innovation as important for improving key operations within the pharmaceutical and biopharmaceutical sectors.
With continuous operation and ongoing inline analysis, process parameters are more closely monitored and maintained at optimal values, leading to more consistent processes and product quality, which in turn can reduce waste generation, product losses and downtime. Because the process runs for long periods of time, smaller reactors can provide large quantities of product. A smaller footprint often equates to lower capital expenditures and can allow for reduced energy, water and raw material consumption, which means lower operating expenses.
Greater automation and reduced human intervention are other important benefits particularly for the production of highly potent APIs and formulated drugs. The smaller environmental footprints of continuous processes are also becoming increasingly important as the pharma industry moves towards implementation of green chemistry principles and considers values such as process mass intensity (PMI) and environmental factors (E-factors).
Minimum cake height is a third of what can be achieved in batch - Improves washing quality
No agitator - No crystal shear!
Automatic wash calculation and dispense - minimises solvent use and reduces waste
Typical moisture content:
Solvent exchanged during process sequence to reduce drying times
Successful industrial product trials with both UK Pharma and Fine Chemical
There are unique benefits for small-molecule production using flow chemistry. Perhaps the most important is the ability to carry out hazardous reactions that would not be possible in a batch process. Because only small quantities of reagents, intermediates and products are present at any given time in a flow reactor, exposure to toxic or energetic substances is minimised, and process parameters such as temperature and pressure can be readily controlled.
Quality - mathematical accurate dosing and wash system ensuring repeatable results meeting the highest standards of cake production.
Safety - Mini batches of high value or volitile API can be easily periodically drawn and tested meeting your codes of practice. Encapsulated system under vaccuum ideal for hazardous material handling.
Validatable - 'Your' credibility, 'our' assurance. Our continuous processing technology is unpresidented.
It is the only validatable end-to-end continuous processing/flow chemistry system available worldwide.
Patented with 20 novel claims.
Control - process and costs
Precision Controllability - The HMI's allow complete autonamy over recipe dynamics. Multi mini batches can be momentarily paused for sampling and corrected if nesscesary. With continuous processing, instead of producing one large scale batch, it creates multi mini batches within the continuous carousel ports. If an API becomes compromised, it is easily detectable as you can make visual checks. If there's ever an issue you lose just a fraction of your valuable API media compared to batch process where losses can be highly substancial and costly.
Slow adoption rates
Despite the clear advantages and real potential, the adoption of continuous process is proceeding relatively slowly. The main reason for this is the need for further technology development. In the biopharma industry, perfusion technology has been available for many years, but practical continuous solutions for down-stream processing have only recently begun to reach the market. Similarly for small-molecule API production, while some downstream processes, such as distillation and extraction, are well suited to continuous operation, others – particularly solids handling – are more challenging.
The lack of clear regulatory guidelines also acts as barrier to adoption of continuous manufacturing. Harmonised guidelines that are accepted by regulatory bodies around the world are needed to ensure that the monitoring of product outputs from continuous processes is conducted in a consistent manner. Additional approvals of continuous processes and experiences with auditing of continuous process steps are required before this situation can be adequately addressed.
Overcoming industry objections. Answering mis-conceptions before they are voiced.
Re-inforcing Continuous USPS...'Unique Selling Points'
Traceability / Regulatory
Providing PROOF that AWL machines deliver proven results.?
What evidence do we have to substanciate our claims
PAT (Process Analytical Technology.
In-line analytical monitoring that provides real-time data is crucial for effective implementation of integrated continuous processes. Not only is the information necessary for maintaining optimum operating conditions at each step, it is also necessary to ensure that changes in one step do not affect other integrated downstream processes.
Continuous crystallisation .....