In an industry that tends to lag behind others on matters of technology transformation, today’s market pressures are creating an increasingly imperative need for change in pharmaceutical manufacturing practices. The pharmaceutical industry is heavily regulated, and therefore, inherently more complex. An overhaul of operations into the digital era can be disruptive to the supply of life-saving medicines.  

However, in order to address the challenges that innovative therapeutics, pricing pressures, and global supply chains present, the adoption of digital solutions has become essential. This means moving beyond all paper-based document management systems, leveraging Big Data, artificial intelligence, industrial internet of things (IIoT), and machine-learning for a meaningful impact on pharmaceutical manufacturing to improve processes and quality.

Cathal Strain, President of Neo PLM, a provider of Product Lifecycle Management solutions for pharmaceutical companies and process manufacturers, discusses the need for change in manufacturing practices and the next generation of technology that can help drive innovation.  –KB

Contract Pharma: What are the latest breakthrough technologies being implemented by pharmaceutical manufacturers?

Cathal Strain: Despite an abundance of innovation in new drug therapies, this century has not seen a corresponding adoption of truly breakthrough pharmaceutical manufacturing technologies. In the small molecule sector—the industry’s largest—continuous manufacturing is now a focus area, especially in new drug development. However, that focus has yet to yield any significant advances. The evolution pattern recalls that of process analytical technology (PAT), whose implementation has substantially lagged expectations after starting with great fanfare in the early 2000s. In the large molecule sector, the rise of single-use technologies is seen as a significant trend, at least for lower-volume manufacturing.

However, none of these initiatives would qualify as a “breakthrough.” At best, the last two decades have been a period of slow evolution for pharma manufacturing in terms of new technology adoption. It is time for Big Pharma to fundamentally change the way it thinks about manufacturing.

There was a time when pharma companies eagerly embraced emerging technologies, such as automation, to evolve their manufacturing operations. That was before the great shift to outsourced production began some 25 years ago. Since then, the industry's appetite for manufacturing innovation has diminished. The manufacturing supply chain remains mired in paper-based processes and production records—starting with initial tech transfer from R&D and continuing throughout the product lifecycle.

CP: How is digitization impacting manufacturing operations?

CS: Digitization, or digital transformation, is the buzzword of this era. However, discussing digitization in pharma manufacturing is difficult considering the paper-based paradigm that continues to dominate shop floors and critical business processes. Many software vendors are casting their products as pathways to digitization, but the same technologies have essentially been available for the past 30 years. These technologies provide a necessary foundation, but the reality is that digitization has not begun to impact pharmaceutical manufacturing operations in a meaningful way.

CP: What are some of the critical factors for success? What hurdles must be overcome?

CS: For myriad reasons, pharma manufacturers must move aggressively to participate in the digital revolution that began in other industries—and the consumer world—over 20 years ago. The biggest barrier to progress is the fact that pharma executives have seen no urgent need to evolve their manufacturing operations. Ongoing innovation is critical in other industries, driving the cost reductions and product quality improvements that companies need to survive and compete. However, pharma manufacturing has not been exposed to those same pressures. The industry can still afford inefficiency and regulatory authorities continue to accept antiquated paper-based processes.

Another hurdle—rarely discussed in the open—is the notion that increasing transparency into pharma manufacturing may reveal problems that could, in turn, present regulatory risks. This attitude must change. Scientists and engineers are driven to uncover and solve manufacturing problems to improve product quality and plant productivity. They can only achieve these objectives with access to comprehensive digital data and advanced analytical tools.

Pharma must make up a great deal of ground quickly to truly enter the digital age:

•    Paper- and document-based business processes, from initial product development through shop floor manufacturing, must become obsolete.

•    Product definition and process knowledge management must be completely digitized. Again, this must occur throughout the product lifecycle, starting with initial tech transfer from R&D. And digital transformation is about more than implementing document management systems. It means placing digital process design, modeling and simulation at the center of the manufacturing systems architecture.

•    Manufacturers must deploy much more robust measurement and control systems on the shop floor. Just as automation has revolutionized other manufacturing industries, recipe-based automation is the only pathway to innovation in drug making. Advanced automation will be an essential component of continuous manufacturing, wherever that technology will be used.

•    With a strong foundation in place, pharma will be well positioned to achieve full digital transformation. Newer technologies that fall under the “Big Data” umbrella—such as cloud-based services, the industrial internet of things (IIoT), artificial intelligence and machine-based learning—will become accessible and drive a new era of innovation.

CP: Taking into consideration the unique challenges the pharmaceutical industry faces bringing operations into the digital era, what steps can it take to minimize the disruption of the supply of medicines?

CS: The dilemma facing pharma manufacturers is digitizing their operations without disrupting the supply chain or raising regulatory concerns. A phased approach to digital transformation can help strike this balance.

We have established the need to replace document-based approaches to tech transfer, process knowledge management and quality assurance with an integrated digital structure that puts process design, modeling and simulation at the center of the IT architecture. This shift is foundational to digital transformation, but will require significant business process re-engineering. The good news is that it can be achieved without negatively impacting shop floor operations. On the contrary, a digital design-centric approach will enhance shop floor operations substantially by automating the creation of recipes for manufacturing execution and control systems.

That said, pharma manufacturers have underachieved when it comes to implementing the shop floor technologies required to enable fully recipe-driven manufacturing operations. The necessary level of process automation cannot be attained quickly. One step pharma manufacturers can take toward shop floor digitization—while not ideal—is implementing MES to achieve a paperless, Electronic Batch Record environment. MES vendors must do their part by providing more innovative solutions that allow customers to deploy EBR cost-effectively. Manufacturers should ultimately be striving for end-to-end process automation. To enable this transition, control system vendors must also make their wares more accessible from a cost standpoint.

Finally, pharma manufacturers must digitize downstream activities such as batch review and release and advanced process analytics. That will open the door to leveraging the technologies driving Industry 4.0 such as IIoT, machine learning and artificial intelligence.

CP: What do you anticipate for the future of the pharmaceutical manufacturing industry?

CS: The FDA issued its industry guidance “Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach” in the early 2000s. That document encouraged the increased use of information and digital technologies—particularly PAT. In the intervening years, initiatives such as quality by design (QbD) and right-first-time manufacturing have received a great deal of attention. Yet for all this discussion, little has changed.

Moving forward, however, the status quo is unsustainable. The workforce is increasingly comprised of those that are digital savvy. Pharma manufacturers cannot expect a laboriously document-intensive industry to inspire the finest engineering minds. To attract top talent, pharma manufacturers must empower their workforces with the best possible tools for the job. That means equipping shop floors with technologies that provide the comprehensive digital data necessary to truly ensure the highest product quality and manufacturing efficiency.

Peter Drucker said, “You can only improve what you can measure.” Taking a step back, it is also true that you can only prove what you can measure—and that includes pharmaceutical product quality. Today’s paper records don’t prove much, no matter how many signatures they bear.

It is time for pharma manufacturers to set their sights on the digital age. I anticipate they will.

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Cathal Strain is CEO of Neo PLM, the company that pioneered digital design-based Process PLM. Cathal founded Neo in 2011 with the vision of bringing third-millennium PLM capabilities to pharmaceutical companies and other process manufacturers. Today, leading pharmaceutical manufacturers are deploying Neo’s technology at sites around the world. Cathal previously spent over 30 years at Pfizer, where he led the design, development and implementation of the world’s first integrated PLM solution for process manufacturing.