In the year 2011, a statement was made at the AAPS annual meeting that experts of today in pharma manufacturing would have no trouble maneuvering through the state of operations prevalent in the 1950s. Less than a decade later, the pharma manufacturing business has grown leaps and bounds. The torchbearer to this progress is the quest for flexible, consistent, efficient and sustainable manufacturing. It is taking the pharma manufacturing industry by storm.
In today's market scenario, the pharma manufacturing industry is directing its forces to counter a number of challenges pertaining to quality, ineffective manufacturing processes and increased regulatory compliance requirements. Key challenges being:
a) $50 billion/year in cost arising from inefficient drug manufacturing processes
b) Increased frequency of drugs in short supply
c) Rising drug recall and quality-related regulatory notifications
In the pursuit to achieve efficient and economical manufacturing outcomes, the pharma industry has evolved to bring about a significant transformation.
Maturing manufacturing technologies
Until recently, single-use technology had very limited usage in the world of pharma manufacturing. With the proliferation of its use for a large number of applications - both in the downstream and upstream processes - this narrative is changing. Single-use technology is driven by the need to lower operating costs, reduce contamination risks and promote the ease of handling. In addition, it offers higher flexibility for facility design and elimination of the clean-in-place operations. Of course, these technologies are also periodically updated to meet growing market demands as well as evolving regulatory compliances.
Modular manufacturing is witnessing a surge in adoption rate owing to its flexibility and economical operating costs. It involves classification of the manufacturing facility into smaller functional blocks or modules that can then be used for the horizontal and vertical expansion of the phases or operations. Apart from the scalability and their ease of movement, there are advantages in terms of reduced validation and potential for re-purposing.
Another groundbreaking innovation is portable manufacturing - the usage of pre-assembled units built elsewhere and then transported to and integrated into the operating facility. Pfizer’s Portable, Continuous, Miniature, and Modular (PCMM) approach to development and manufacturing takes this a step further. The modularity aspect is inherent in the PCMM – different components of a production line are produced as individual modules at different locations and then shipped to a central location to be assembled. GE Healthcare’s KU Bio - a configurable, integrated, single-use biomanufacturing platform fitted with services like HVAC, Electrical and Plumbing – is an example of pre-fabricated modules that can be used both as a new facility or to rapidly scale up an existing facility or module.
However, the biggest shift would be the transition to Continuous Manufacturing, a combination of enabling technologies that need to work together cohesively and in tandem achieve quality and commercial viability, as well as manage the inherent risks from environmental conditions. This is, driven by speed-to-market consideration based on scalability, reduced CAPEX, better performance criteria (e.g. Yield and Cycle Time), consistent product quality and improved sustainability/environmental considerations. This is a great opportunity for the industry to blend the manufacturing technology with other allied products and vendors to accelerate technology adoption and drive uniform standards. However, the technology and processes needed to make drug-based products need to be continuously developed and subsequently demonstrated commercially. While the smaller molecules have a smaller challenge given the history in the chemical industry, the story is different for biopharma. The newest kid on the block is Additive Manufacturing, popularly known as 3D Printing. The process for 3D printing facilitates tailoring the size, and aids improved or consistent drug release profile. While there is the first FDA approved 3D printed drug and the Regulatory Agencies have guidance and regulations to support faster adaption of such emerging technologies, the path to large scale adoption appears to be a long way for now.
Journey so far and the road ahead
Each of these manufacturing technology segments is at a different level of maturity and possibly needs other developments before they become commercially available.
● Single-use technologies are heavily exploited today and provide the benefits of smaller, more flexible and often modular facilities and rapid scaling.
● Portable manufacturing, on the other hand, is expanding with the USP of lift and shift capability and the use of prefabricated or pre-engineering modules for specific unit operations.
● Additive manufacturing is in its exploratory stage holding the promise of ‘make on-demand and make local’ while holding the potential for recipe securing.
● Continuous Manufacturing is an emerging technology. The high potential to resolve batch-to-batch variability, enable real-time release, and reduce manufacturing footprint make it an attractive proposition.
The industry, however, has been traditionally averse to change and from the Business 4.0 perspective, it needs to embrace risks to remain relevant. Collectively these technologies have the power to transform the pharma and biopharma manufacturing ecosystem with the potential for significant value creation and newer business models.