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The Next Generation of Biotech Manufacturing

Biologic medicines are complex and hard to make, which helps to explain why biotech manufacturing plants are huge and expensive to build. Amgen scientists have created a new biomanufacturing paradigm that is leaner, greener, more flexible and productive, and less costly to build and operate. The next-generation technology is advancing Amgen’s goal of bringing the biotech revolution to more patients around the world.

Throughout the early decades of the biotechnology industry, one of the biggest hurdles involved in making a biotech drug was making enough of it. Unlike conventional pills and tablets made through chemical processes, biologics require the protein-producing machinery only found in living cells. But it’s difficult to coax cells into making large amounts of a protein, and the yields from the early processes used to generate biologics were often meager.

To ensure that patients would not have to wait for a medicine due to insufficient supplies, biotech companies built huge manufacturing facilities. Today, a typical biotech manufacturing plant contains more floor space than a dozen football fields, with a footprint that often includes separate buildings for quality testing, utilities, and a warehouse. The medicine-making cells are grown in massive stainless steel bioreactor vessels, and the process of feeding the cells and extracting the protein is supported by miles of pipes.

While the current generation of biomanufacturing plants has greatly increased the supply of biologic medicines, the cost of this investment mirrors the size of the plants themselves. A conventional facility can take four years and more than a billion dollars to construct. That cost represents a steep hurdle to overcome as the biotech industry seeks to expand its manufacturing base and reach more patients in regions around the world.

From visionary concepts to reality

About 10 years ago, scientists at Amgen began to brainstorm more efficient and economical ways to manufacture biologic therapies. In laboratories and pilot plants, they started to test new technologies that could make the process leaner, greener, faster, more productive, and less expensive (see video above). Inside Amgen, this effort was first known as “Manufacturing of the Future,” a term that was dropped when the vision for the future began to overlap with the present.

The new paradigm can be seen at Amgen Singapore Manufacturing (ASM), a biomanufacturing plant unlike any previous plant. ASM is the first commercial facility to incorporate next-generation technology and processes. The plant’s formal opening took place on November 20, 2014—just 17 months after ground was broken to mark the start of construction. The validation process needed to start commercial production is well underway.

“The benefits of next-generation biomanufacturing are immense,” said Amgen Chairman and CEO, Bob Bradway. “We are able to build one of these new facilities at a quarter of the cost and in half the time of a conventional facility, and we think we can operate it at one-third of the operating expense.”

In addition to saving money, the Singapore plant solves a problem inherent in standard facilities. “Conventional plants are often built around a single product, and everything needed to make that product is welded into place,” said Alison Moore, Amgen senior vice president, Process Development. “To ramp up production of another product, you need to retrofit the facility, so it is costly and complex to adjust to a changing product portfolio or changing demand. Most importantly, that impacts the speed at which a drug is available for sick patients.”

To solve that problem, the Singapore plant has adopted a flexible, modular design. Conventional facilities use fixed bioreactor vessels that hold up to 20,000 liters of cells and growth media. By contrast, ASM will deploy 2,000-liter vessels that are portable and accommodate single-use bioreactor bags. Thanks to higher-yielding cell lines and more productive cell culture processes, these smaller, modular bioreactors can produce as much protein as the massive tanks currently used at conventional plants.

Flexible plants to support Amgen’s research strategy

Most importantly, though, the modular design will enable plant operators to easily switch between different types of equipment to make different products. That’s a critical capability for Amgen because the company now employs 11 different drug modalities, or structural formats.

“Amgen’s research teams employ a ‘Biology First’ approach, where we strive to understand the biology of a disease before designing the right medicine to treat it,” said Moore. “That’s a core strategy, and we don’t want our scientists to be constrained in the types of drug modalities they can use. Our manufacturing infrastructure needs to support this strategy, and a key way for us to do that is to have modular manufacturing.”

The Science Behind
Next-Generation Biomanufacturing

A look at the key scientific and technical achievements that have enabled Amgen to introduce a new biotech manufacturing paradigm in Singapore.

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The smaller bioreactors will also accelerate technology transfer between Amgen’s pipeline and ASM. Commercial production in Singapore will be done at the same scale using the same processes and technology as Amgen’s clinical supply facilities. “That will greatly reduce the time and expense of scaling up new processes and transferring them from smaller pilot plants to commercial manufacturing plants,” said Moore. “Eventually, a facility like Singapore could be used to make both the clinical trial supplies and commercial supply for some of our medicines.”

The modular, compact design will also lower the plant’s environmental impact. With a footprint of just 120,000 square feet, ASM will provide major decreases in energy expenses as well as reduced carbon emissions and solid waste. Single-use bioreactors will also greatly reduce the amount of water needed to clean and sterilize equipment.

Some of the new technologies being implemented in Singapore are also being adapted to make Amgen’s other facilities more efficient, said Esteban Santos, executive vice president for Operations. “We are enhancing our manufacturing technology and processes across our network to help ensure that we can deliver for patients today and in the future.”

Every patient, every time

As the biotechnology industry expands globally, millions of additional patients will be gaining access to biologic medicines. This growing demand for treatments, combined with cost constraints and increasingly complex global supply chains, have put pressure on the industry’s ability to manufacture adequate supplies to meet patients’ needs.

“Patients around the world depend on Amgen to reliably provide high-quality medicines,” Santos observed. “We have an outstanding track record, and our teams around the globe are working very hard to ensure we continue to deliver for patients.”

Next-generation biomanufacturing represents a comprehensive solution to many of these challenges. A facility like ASM is sized to ensure supply for the global market, but smaller plants can also be built to meet the needs of specific regions or countries. “Over time, our manufacturing network could evolve from one that is dependent on a couple of large anchor sites to a more dispersed network that includes small, fast-to-construct, easy-to-operate plants that ensure local supply of our medicines,” said Madhu Balachandran, an executive vice president who oversaw the development of the new strategy at Amgen. “That would greatly facilitate our expansion into countries where biotechnology has yet to realize its potential. I don’t think we have fully imagined all the benefits that could accrue from the next-generation biotech manufacturing as it matures.”

For more information about the science of biotech manufacturing and Amgen’s capabilities, visit www.amgenbiotech.com.

USA-CRP-042597