The need to save time and money in pharmaceutical development has never been greater
Regulators are making even more stringent demands for larger and longer clinical trials that give better proof of efficacy and are more likely to pick up safety signals. With ongoing cost pressures across the business, companies are always on the lookout for strategies and methods that might accelerate a product’s journey from idea to marketing authorisation, reducing R&D costs and maximising the length of time a product has to recoup its development costs before its patent expires and it’s exposed to generic or biosimilar competition.
Although meeting the demands of regulators must always remain at the forefront of a business’s strategy, there are numerous areas in which time savings might be made. One such area is in the manufacturing of the drug product. By introducing more flexibility into the manufacturing chain, it can be possible to give better efficiency, reliability and greater speed to market.
Advances in manufacturing technology are key to achieving this, although it is important to note that there must always be a good reason for making changes and improvements. Examples include projects that will reduce costs in areas such as labour, materials, logistics or downtime, or a combination of these factors. It might be designed to increase efficiency, improve a process’s yield or quality, or optimise a product’s availability or cycle time. Enhanced reliability is also an appropriate driver, as this can provide improvements in uptime, productivity or even a facility’s capabilities. And, finally, there is safety. This might be the safety of the patient taking the drug, the employees within the facility or even removing risks to the business or to future regulatory approval.
Any pharmaceutical company has a number of key manufacturing decisions to make for each individual project. How and where and by whom will that product be manufactured? Once that is decided, challenges still remain. Customised solutions may be required for specialty products or individually targeted treatments, and complex formulations might be necessary if a product with, for example, low bioavailability or that is highly potent, is to be delivered successfully. Commercial factors may also necessitate particularly aggressive project timelines.
Flexible manufacturing processes can assist in achieving these demands. They can also go a long way towards meeting unknown future needs that might be caused by uncertainty in what the company’s product portfolio will contain going forward.
The first step when deploying new manufacturing technology is to develop a thorough understanding of the current model. Typically, this involves a push model, with the aim being to meet new product introduction demands. However, this can prove costly, and may not be ideally “scaled” to meet all the specifications of an optimal manufacturing solution as the product is commercialised. A more efficient pull model is likely to be preferable. By focusing on the full list of requirements and pulling them together at the outset, the selection of optimal technologies, from machines to handling equipment, conveyancing and process flows, can be made in such a way that all of the requirements will be met.
The second step is to gain a deep understanding of the process or processes, and the available equipment and capacity. What is the production volume and how many units are there? What is the line speed rate and what is the restart capacity? What are the operation costs per hour or per unit, and are the overall production costs known? Furthermore, it is helpful if any potential breaking points or bottlenecks can be identified in advance. These might include operator expertise and other continuity risks, including market competition and any inputs, for example, when there is just a single supplier.
Third, developing a similarly good understanding of both products and customers will determine what is driving the need for new technologies and, therefore, any points at which a particular focus is required. If, for example, a new product introduction is the driver, then regulatory, project and risk management will be important. Alternatively, if the technology introduces the capability to manufacture a specialty product, such as one that is highly potent, then cost, engineering and employee health and safety issues will be to the fore, as well as time and regulatory constraints.
Once all this understanding has been acquired, the fourth step is to develop a manufacturing technology strategy and ascertain how it will fit with the overall aims and drivers of the business. How is continuous improvement in technology perceived, and what elements of the new strategy are best aligned with those existing values? If it is to succeed, the strategy must be carefully explained to the company’s leadership and the wider business. The starting point for this should be the short-term gains that will be made, followed by the long-term aims and benefits that the manufacturing technology strategy will bring to the business.
The fifth step is to develop a manufacturing technology roadmap. If this is done in a visual way, it will assist in providing a wider understanding of the project. It should communicate the overall business advantages it will offer, highlight pilot projects and reflect what the implementation should achieve and when. This roadmap should be aligned with the strategic plans. By splitting the process down into smaller components, it should be possible to show the industrial and value engineering aspects for individual business units, for a specific geographical location, or even for an entire manufacturing facility.
Step number six is to put the roadmap into action, by developing a deployment plan. This plan should be designed to communicate what is being done and to ensure that the plan fits in with the company’s goals and culture, and of course, what customers require. The ideal location for the deployment will depend on what those customers are looking for and where.
Finally, in step seven, ways in which the plan can be accelerated should be sought. This is best achieved via the discipline of project management.
Catalent’s manufacturing facility in Winchester (Kentucky, USA) is a mainstay of the company’s production capabilities, producing more than three billion tablets and capsules annually, and being responsible for the launch of more than 100 new products into the market since its inception.
Five years ago, it reached capacity and expansion was required to ease those volume constraints, as well as providing additional space to serve future expansion demands, including dedicated, custom manufacturing suites for specific customers. Such dedicated suites are an important way in which very specific customer requirements can be met. Their design involves Catalent working closely with the customer in a cross-functional team to create a list of process requirements. Usually, these will be dependent on the nature of the product, and can include environmental conditions such as the temperature and humidity, pressure differentials and the amount of space that will be required to make the product efficiently and securely.
One way to maximise future flexibility is to ensure that, at the outset, the shell space is designed in such a way that all conceivable requirements can be met. This includes the ability to expand the space to increase capacity, as well as the full range of services, including hot and cold water, a steam system, compressed air lines and air handling systems. Even if they are not required in the first instance, it is significantly cheaper to have such services in place at the outset, rather than having to re-engineer the space to install them retrospectively.
The initial stage of the Winchester expansion included the addition of three further processing suites, with capacity for fluid bed processing and encapsulation. A 50% increase was made to the laboratory space, alongside a significant increase in warehouse space that was sufficiently large to permit additional future expansion too.
A further, $52 million expansion was completed in 2015, with the installation of an additional fluid bed processing capacity, expanded analytical laboratories and an advanced, open facility design that provides flexibility to support the requirements of new customer programmes. Since that expansion, Catalent has announced an exclusive long-term supply agreement to produce Pfizer’s leading over-the-counter heartburn treatment, Nexium 24HR (esomeprazole), also marketed as Nexium Control outside the US. At the site, Catalent will formulate and manufacture the 20 mg proton pump inhibitor drug into enteric coated, delayed release pellets, using the installed fluid bed technology.
The ongoing focus on manufacturing technology is an important factor in being able to provide a faster, more efficient service to customers. If a particular technology is already in place and the capacity is there, it allows production to start very quickly. If new technologies are required, with an empty shell ready for fit-out (or a currently unused fitted-out suite that can be repurposed), the capacity can be online within 6–8 months. This is in stark contrast to the lead time for additional capacity that is being built from scratch, which will typically take 12–18 months to construct. There is, therefore, the potential to file and reach market up to a year earlier.
Of course, compliance must be at the forefront when designing the facility, and the process suites with the product in mind, with other considerations including the optimisation of the flow of both people and materials. By focusing on flexibility in manufacturing technology and laying the groundwork for rapid future expansion when required, that all-important speed to market can be optimised.