Times are changing, and with it, the ways the pharma industry used to operate are also changing. The so–called ‘’conservative’’ pharma manufacturers are now looking beyond the traditional manufacturing model, exploring new avenues to accommodate unexpected sales forecasts and small volume production. As novel drug delivery therapies are evolving with time, pharma manufacturers now need manufacturing capabilities that are versatile enough to accommodate the market’s uncertain requirements and are more responsive. Flexible manufacturing is emerging as an apt solution that can overcome these challenges successfully.   

Why flexible manufacturing  

Traditional manufacturing setup comprising different equipment pieces for different processes are no longer enough to meet the production requirements of new drug products with small volume. Not only is this mode inefficient, but it also calls for more financial and physical resources. Also, the following trends emerging in the pharma landscape demand a versatile approach towards manufacturing to gain more efficiencies. 

1. Fast-track drug approval programs – Orphan drug development is currently in vogue because of the incentivisation by the regulatory agencies, the overall expedited drug approval process, and the exclusivity of these molecules. The shortened clinical development phase means the sponsors and CMOs must complete the chemistry, manufacturing and controls development, scale-up, process validation, tech transfer, and stability testing rapidly after the initial regulatory approval is obtained. To reach the market first is another reason why pharma companies aim to quickly wrap up their clinical and formulation studies. 

1. Commercialisation of biopharmaceuticals – In the past few years, the demand for biological molecules, immunotherapy, cell and gene therapy has increased significantly. However, manufacturing such biopharmaceuticals on a larger scale is still a challenge for many manufacturers because of the lack of previous track record and limited commercial success.   

1. Unpredictable sales forecasts – The new drug delivery therapies, including orphan drugs and biopharmaceuticals, are highly potent and are usually targeted to a small patient group. To manufacture such small volume, expensive drugs require a flexible production setup. Further, forecasting the final sales volume of such products is quite a challenge and involves volatility.  

1. Need for a balanced approach for the stakeholders – Currently, a large number of pharma companies outsource their products through CMOs, and the uncertainties in market demand can affect both of them. Sponsors can end up in either oversupply or undersupply of the finished product to the market, whereas CMOs can lose on the new opportunities because of the money tied up in costly goods and expensive inventories. A middle ground is required to provide favourable results to both the stakeholders.   

Different approaches to flexible manufacturing  

• Modular manufacturing   

Many pharma companies are opting for modular manufacturing capabilities to produce a wide variety of products from a single facility. Such an approach offers several advantages, such as accelerated equipment commissioning, faster changeovers, high versatility, and improved overall equipment effectiveness (OEE). The ‘’ballroom’’ concept of modular manufacturing involves using a large manufacturing area with no fixed equipment. The existing facility is broken down into modules to facilitate standardisation, simplified processes, re-use of designs, and actual modules in different implementations. The ballroom concept provides many benefits such as plug-and-play functionality, lower capital costs, a small manufacturing footprint, and reduced need for dedicated cleanroom space. Another concept of modular manufacturing is prefabricated manufacturing pods. These podular equipment systems are movable, faster to build, and can be assembled into multiple configurations. 

• Data-driven manufacturing  

The evolution of industrial revolution 4.0 is shifting the paradigm of traditional pharma manufacturing. The ‘’big data’’ and ‘’IoT’’ platforms provide excellent opportunities to the pharma manufacturers to convert the routine operational data into valuable insights and intelligence. Based on this knowledge, pharma companies can adopt proactive management mode and develop new strategies to optimise production and mitigate risks. With real-time process visibility, manufacturers can control the operations more efficiently and do better planning.    

• Single–use manufacturing – This technology has proved invaluable for manufacturing biopharmaceuticals. Single-use bioreactors are relatively quick and easy to install and are now widely replacing the traditional large steel-tank bioreactors. The fluctuations in the market demands can be easily accommodated by expanding or reducing the capacity of single-use bioreactors in a timely manner. Product changeovers and cleaning are faster than steel tanks, thus allowing the rapid start of a new production batch.   
• Continuous manufacturing – Compact-scale, capable of integration with in-line process analytical techniques, and highly adaptable, continuous manufacturing is becoming quite popular amongst pharma manufacturers. The inherent flexibility of continuous manufacturing allows a large quantity of product manufacturing within a much lesser time than a conventional setup. Pharma manufacturers can supply the product in response to just-in-time market requirements instead of maintaining extensive inventories to meet the spikes in demand. 

The way forward 

The diverse, complex product portfolios and uncertain, volatile market scenarios have forced pharma manufacturers to consider one more factor along with time and cost – flexibility. Fortunately, the progress in technology and the rise of IoT platforms have provided the pharma industry enough means to develop new strategic manufacturing concepts that would meet the current challenges. Flexible manufacturing definitely has the potential to accommodate the future demands of the pharma manufacturing set up and take it to the next level with outstanding results. The only question is how much the pharma industry is ready to embrace this new approach.