Pressure to reduce costs, improve efficiency and reduce time to market is reflected in changing demands for manufacturing equipment, according to the latest research by Nice Insight
The main driver influencing all aspects of the pharma industry is the growing downward pressure on costs. Shifting markets, the end of the blockbuster era, government healthcare mandates and the linking of insurance reimbursement with medical outcomes are all affecting drug pricing around the world. In response, pharma companies are taking a range of different actions to reduce their costs and increase efficiency and productivity.
The recent significant rise in mergers and acquisitions is one mechanism by which companies hope to reduce costs through synergies and access to new therapeutic classes and/or regional markets. Outsourcing of manufacturing is on the rise, as is the use of third-party service providers for business activities traditionally considered core to sponsor companies, such as logistics.
Equipment needs across the value chain are changing, from initial discovery efforts to the packaging of final products
Interest in continuous processes is also intensifying, and emphasis is now on the deployment of equipment and technologies that enable higher production yields, the reduced need for purification and more rapid scale-up and commercialisation. As a result, equipment needs across the value chain are changing, from initial discovery efforts to the packaging of final products.
At the same time, the surplus equipment market has experienced strong growth due to the increased availability of high-quality equipment and the need of contract and generic manufacturers, and even branded drug companies, for low-cost equipment solutions.
Single-use, or disposable, technology is widely used in biopharmaceutical drug development, and more recently has begun to gain acceptance in biologics production at increasingly larger scales, including for commercial manufacturing. This interest is driven by the advantages that disposable technologies provide in terms of decreased capital expenditures and operating costs due to the reduction of cleaning and sterilisation steps and the need for validation. In addition, processes based on single-use equipment are more flexible, require shorter set-up times and have significantly reduced cross-contamination risk, all of which translates to a faster time to market and more robust and reliable production.
Numerous types of single-use bioreactors are employed for the production of the major types of biopharmaceutical products, including recombinant proteins and monoclonal antibodies. Different designs are also available for batch, fed-batch and perfusion reactions.
Disposable, technology has begun to gain acceptance in biologics production at increasingly larger scales, including for commercial manufacturing
While the initial focus was on the development of disposable technology for upstream processes, single-use formats are now available on the market for many downstream bioprocess steps, including filtration and chromatography. For instance, modular, disposable tangential flow filtration (TFF) systems can be readily integrated for the concentration of downstream biopharmaceutical process streams.
In fact, many newer single-use systems are designed for use in continuous bioprocesses, and disposable technology is an enabler for the implementation of fully integrated continuous biopharma production. Continuous manufacturing is attractive because it leads to more consistent products and processes, which equates to the consumption of fewer resources (raw materials, energy, water) and less waste generation, for lower operating costs. Capital costs can be lower as well.
For upstream biopharmaceutical manufacturing, perfusion has become a well-established process that affords high quality biologic drug substances with high productivity. Other types of upstream equipment under development include continuous centrifuges, acoustic resonance devices, and cell settlers.
For continuous downstream bioprocessing, simulated moving bed chromatography and, as mentioned above, TFF systems, are also available and being adopted by the industry. New flow-through absorbers are also being developed for integration with chromatography and virus filtration steps. Advances in process analytical technology (PAT) systems are also crucial to the successful implementation of integrated continuous bioprocesses.
The benefits of continuous processing are not limited to biopharma production. In fact, the industry has recognised the value of flow-through chemistry for the production of APIs and continuous tableting for many years. Although widespread adoption of continuous processing for small-molecule intermediates and APIs has not yet been achieved, most pharma companies and contract manufacturing organisations (CMOs) have the capability to perform continuous-flow chemistry at commercial scale using microreactor technology.
In addition to enhanced process and product consistency, flow chemistry enables manufacturers to perform hazardous reactions or use challenging conditions not possible in traditional batch modes. For example, highly exothermic reactions or reactions that involve highly reactive reagents can be performed using flow chemistry because only very small quantities of reagents and products are present at any given time and control of the reaction conditions is much greater.
On 20 April, the research branch of That’s Nice, Nice Insight, published results from its latest industry survey on Pharmaceutical Manufacturing Equipment. These buying trends are from the new study
In addition, because scale-up generally involves the use of more of the same microreactors in parallel, it can be achieved much more quickly without the need for extensive studies, and production can be flexibly scaled to meet demand. As with biopharma, reduced resource consumption and waste minimisation are additional benefits.
In fact, pilot- and small commercial-scale equipment with built-in parallel microreactors is now available for larger-scale continuous processes. Microreactors for the continuous processing of liquid/solid and multi-phase systems are also under development and offer the potential to expand the applicability of the technology. Efforts are also directed towards the development of continuous separation and purification technologies that have not traditionally been designed for this type of operation, particularly with respect to solids handling, and much progress has been made, particularly with continuous crystallisation at larger scales.
Flow chemistry enables manufacturers to perform hazardous reactions or use challenging conditions not possible in traditional batch modes
Effective online analytical capabilities are also leading to increasing implementation of online tableting systems for small-molecule drug product manufacturing. In this case, continuous processes generally have fewer steps and therefore reduce manual operations, which leads to increased productivity and safety. Again, better process control leads to improved product consistency and quality.
The smaller footprint of continuous tableting processes also leads to lower capital costs. Overall development times tend to be reduced as well. Recent enabling equipment technologies have included systems designed for the accurate handling of poorly flowing solids, even at very low material volumes. Progress has also been made in the development of the intelligent feed-forward and feedback loops and control systems that are required for the complete integration of all steps in the tableting process.
One of the fastest-growing segments of the pharmaceutical market is formulated drugs based on highly potent active ingredients (HPAPIs). This is largely attributed to the growing number of antibody-drug conjugates (ADCs) that have recently been approved or are in development. However, the highly potent components of ADCs must be manufactured in facilities with equipment and procedures designed to mitigate the risks they present. As the need for such specialised equipment has increased, innovative equipment manufacturers have begun to work with process engineers at HPAPI producers to develop systems with the necessary protective functionality.
Increasingly, HPAPI manufacturers are relying more on isolation and containment through equipment and facility design
Increasingly, HPAPI manufacturers are relying more on isolation and containment through equipment and facility design, and less on personal protective equipment. For instance, not only are reactors available in contained systems, but downstream purification equipment, including balances, rotary driers, pressure filter driers, and slurry vessels are being installed in isolators that meet exceedingly low occupational exposure levels. In the future, if single-use systems can be developed that are compatible with organic solvents, disposable technology would probably prove highly beneficial to HPAPI manufacturing.
At the same time, demand for used pharmaceutical equipment is also rising as the result of increased levels of industry consolidation and outsourcing. Companies acquiring or merging often turn to resource recovery (the sale of redundant facilities and equipment) to achieve initial and ongoing cost savings. Simultaneously, CMOs must rapidly expand their capacities to meet the requirements of sponsor companies that are outsourcing to achieve further cost savings and gain access to specialised technologies and capabilities.
Increasing demand for generic drugs, particularly in emerging markets, is also pushing these manufacturers to seek sources of readily available, low-cost process R&D, processing and packaging equipment. In fact, high-quality used equipment is often sold at 40–50%, and sometimes as little as 20%, of the original price. In addition, used equipment is immediately available.