Drug Making Breaks Away From Its Old Ways

By Jonathan D. Rockoff

For decades, drug makers have used cutting-edge science to discover medicines--but manufactured them using techniques dating to the days of the steam engine.

But now, the industry is moving toward a major upgrade. GlaxoSmithKline PLC, Johnson & Johnson and Novartis AG are among the companies building facilities to make drugs differently. Biotechs including BioMarin Pharmaceutical Inc. and Vertex Pharmaceuticals Inc. are deploying--or about to--elements of the processes in their production.

Under the new approach, raw materials are fed into a single, continuously running process. Many other industries adopted such a "continuous-manufacturing" approach years ago, because quality can be checked without interrupting production--with weeks shaved off production times and operating expenses cut by as much as 50%.

Until recently, pharmaceutical companies have been stuck making drugs the old-fashioned way, mixing ingredients in large vats and in separate steps, often at separate plants and with no way to check for quality until after each step is finished. Any desire to modernize was partly blunted, industry officials say, by the high margins netted on the industry's string of billion-dollar-selling drugs.

But companies have lost most of their sales from those blockbusters due to competition from low-price generic versions, prompting a hard look at their operations and expenses. It also helps that industry officials expect that the Food and Drug Administration, once viewed as a potential obstacle because it must sign off on a company's drug manufacturing, will support the moves.

The FDA, seeing an opportunity to "improve the overall quality" and reliability of drug manufacturing, began pushing for change in 2004, said Janet Woodcock, who heads the agency's drugs center.

"The pharmaceutical industry has been so slow to adopt approaches embraced by other industries, but I think the time is now," FDA Commissioner Margaret Hamburg said during a tour of Vertex's new continuous-manufacturing line in South Boston, which would be one of the first such facilities to go into production if a new cystic-fibrosis drug gets approved in mid-2015.

A key challenge companies are confronting: developing the expertise and skills to run the new kind of production, said Paul McKenzie, who had overseen J&J's drug manufacturing before taking over the company's medical-device R&D this year.

At a factory in Puerto Rico, J&J has built a line that could manufacture the HIV/AIDS medicine Prezista starting in 2016 using the new techniques, if regulators approve. The main ingredients will still be made elsewhere, but J&J aims to manufacture 70% of its "highest-volume products" using the processes within eight years, Mr. McKenzie said.

Meantime, GlaxoSmithKline is building a $29 million continuous-manufacturing facility in Singapore to make respiratory-drug ingredients, starting in 2016. "The industry has a lot more quality and cost pressure now, so we need to transform our manufacturing paradigms," said Mark Buswell, Glaxo's head of advanced manufacturing technology.

J&J, Glaxo and most other companies remaking their manufacturing intend to use the new approach for the final stages of drug production, not the manufacture of ingredients. However, Novartis is building a line at a Swiss plant that would make drugs continuously from the start of ingredient production through the end of coating tablets, according to Markus Krumme, who heads Novartis's continuous-manufacturing unit.

The upgrades should substantially reduce the risk of product-quality failures, because companies will be able to make any needed corrections throughout production, not just after a batch is finished, officials said. The changes will also cut waste because companies won't need to throw out entire batches if a problem turns up. And production times will drop since the steps will no longer be performed separately, often in different places.

As a result of such benefits, companies will save an estimated 30% or more in operating costs, according to Bernhardt Trout, director of the Novartis-MIT Center for Continuous Manufacturing, which has been developing the new technologies with funding from Novartis.

Continuous-manufacturing plants themselves are expected to cost much less than the $150 million that a traditional drugmaking factory costs because they require less equipment and less space, said Marcus Ehrhardt, who leads PricewaterhouseCoopers' life-science operations business.

The Vertex facility's linked pipes, valves and hoppers take up only 4,000 square feet, compared with a 100,000-square-foot traditional factory, said Hayden Thomas, a Vertex manufacturing official. If the company's new cystic-fibrosis drug gets approved, the facility would make 100,000 tablets in an hour, rather than the four to six weeks that would be needed to make a batch at a traditional plant.

The biotech had been using contract plants to make its drugs. In early 2012, the board decided the company should build its own, continuous-manufacturing plant, despite a cost exceeding $30 million, because its speed would enable the company to make high volumes of cystic-fibrosis tablets as soon as the drug got approved, said Vertex Chief Executive Jeffrey Leiden.

Dr. Leiden said there were "hiccups" erecting the new plant, including the challenge of designing software to run the complex machine. To reduce the risk that the plant wouldn't pass FDA muster, Vertex said it consulted the agency throughout the plant's design, construction and testing.

Write to Jonathan D. Rockoff at Jonathan.Rockoff@wsj.com

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