Large Molecule

Quality Management in the Digital Age

An operational approach such as Pharma 4.0 that connects all resources via the Cloud can be a really good thing

By Ethan Smith, senior director, Vault QualityDocs, Veeva Systems

Rapid changes in molecular science have ushered in a new era of innovative biopharmaceuticals. The emergence of targeted therapies, the increased prevalence of large molecule medicines, and huge growth in the number of treatments for orphan diseases are just some of the factors that are having a significant impact on how medicines are created and manufactured on a large scale. Life sciences companies are replacing the one-drug-fits-all approach for average patient populations with more personalized therapies. In fact, 42 percent of drugs in the pipeline today are personalized medicine, according to a survey by the Tufts Center for the Study of Drug Development.1

These specialized drugs that give smaller patient groups the best therapies based on their genetic makeup and other predictive factors are replacing blockbuster mega-drugs designed to treat larger populations. For instance, the few drugs used to treat high cholesterol in the past have since splintered off into many targeted therapies based on the genetic variables of specific patient populations. This approach springs from discoveries in genomics − the structure, function and mapping of human genomes − and it’s giving rise not only to targeted therapies, but also to highly specialized diagnostic tools and personalized therapeutic drug monitoring.

A powerful example of personalized drug development in oncology is Zykadia, an inhibitor designed for patients with advanced non-small-cell lung cancer who have a specific gene mutation that causes tumors to become resistant to existing treatment. The drug, developed by Novartis, is targeted at very specific patient populations. The approval was lauded by the FDA, whose director of the Office of Hematology and Oncology Products noted, “today’s approval illustrates how a greater understanding of the underlying molecular pathways of disease can lead to the development of specific therapies aimed at these pathways.”2

VAST POTENTIAL FOR TARGETED DRUGS
Due to the enormous potential of these therapies, the White House has requested an initial budget of $215 million for its precision medicine initiative. President Obama believes “the possibilities are boundless” for specialized drugs and his administration aims to collect genetic data from one million Americans so scientists can develop therapies tailored to individual patients.3

In response to the shift to targeted drugs, many large life sciences companies have started to diversify their product portfolios to include these medicines. One powerful motivation for this change is financial returns from traditional drugs are shrinking in the face of increased competition from generics. Nearly 88 percent of prescriptions now filled as a generic in comparison with just 49 percent in 2000.4

While specialized therapies can produce better outcomes for patients, they also present manufacturing challenges. For example, targeted biologics are typically larger than small-molecule medicines and are often derived from living cells, resulting insignificant challenges to manufacturers. Personalized medicines are typically made in small batch sizes and have a wide variety of product variants. Small-batch production can be cumbersome because after every production run, equipment must be stopped, reconfigured, tested, and validated before the next batch can be produced. The downtime from such stoppages impacts efficiency and time-to-market. The FDA has tried to address batch-to-batch quality requirements for years and plans to provide incentives to companies that raise manufacturing quality. When it comes to regulating small batch sizes, documentation is especially critical because it helps capture a detailed picture of each step for staff and outsourced teams globally, and for inspectors.

CHANGE IS ESSENTIAL
Life sciences companies that don’t make changes to stay at the forefront of targeted medicines will struggle. A major part of those changes is revamping operations by implementing “Pharma 4.0,” a concept which has the potential to revolutionize operations from the inside out.

Pharma 4.0 is an operational approach that connects all resources − human, informational, and technological − in one virtual network. This connectivity extends from within the company to beyond its walls and combines diverse technologies such as cloud computing and big data analytics. Pharma 4.0 helps companies transition from robust but inflexible mass-production processes to more agile, highly automated methods that create tailored products quickly and cost-effectively.

In contrast to Pharma 4.0, many life sciences companies still store and disseminate manufacturing information on paper. This increases risk and slows down quality-control processes by limiting knowledge sharing and hindering collaboration among employees and partners alike. The latest cloud-based content management applications free managers to quickly route quality content and data throughout the entire company and vendor ecosystem using an efficient system for review and approval. Because all data are in cloud-connected systems staff have the visibility and access they need to monitor key performance indicators, guide the manufacturing process, and respond to incoming patient data that triggers the production of personally tailored medicines.

Pharma 4.0 also aligns with the business world’s migration away from the desktop to the flexibility of mobile devices. Accessing information stored in the cloud via smartphone, for example, enable managers to work more efficiently by reviewing and approving quality content and data virtually anywhere.

In recent years, scientists’ deepening understanding of the biologic causes of disease has created unprecedented opportunities while simultaneously changing many aspects of drug development. There is huge potential for personalized medicine to revolutionize the treatment paradigm for patients, but the development of these increasingly precise treatments is also highly complex, resulting in changes in the way medicines are identified, studied, and manufactured. It requires nothing short of an operational transformation from the outbound flow of goods to the information flow back of real-time patient data. Such a drastic change can lead to disruption and uncertainty, at least for a time. But, by adopting Pharma 4.0, companies can successfully evolve and safely manufacture high-quality, precisely tailored medicines that give patients better lives.

REFERENCES
1.“Study of Disease and Development,” 2014, Tufts Center for Disease, For more, visit: http://www.phrma.org/sites/default/files/pdf/pmc-tufts-backgrounder.pdf

2. FDA News Release, U.S. Department of Health and Human Services, For more, visit: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm395299.htm

3. “Fact Sheet,” issued by The White House Office of the Press Secretary, January 30, 2015. For more, visit: https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative

4. “2015 Biopharmaceutical Research Industry Profile,” published by Pharmaceutical Research and Manufacturers of America (PhRMA), Washington DC, April 2015. For more, visit: http://www.phrma.org/sites/default/files/pdf/2015_phrma_profile.pdf

ABOUT THE AUTHOR
Ethan Smith is senior director, Vault QualityDocs, at Veeva Systems. He has extensive experience in content and business process management, developing and delivering innovative solutions to top tier life sciences organizations across the value chain from research and development to commercial operations, regulatory affairs, and quality and compliance. Ethan has held a variety of leadership roles in the consulting practices of Business Edge Solutions, PricewaterhouseCoopers, BearingPoint and Andersen Consulting, and holds a Masters of Public Health from Emory University and a BA in History of Medicine from the University of Pennsylvania.

He can be reached at ethan.smith@veeva.com.