Masters of efficiency

CORBIS

The story of a pharmaceutical reads a bit like a fairy tale. There's good and evil (the medicine and the disease), the battle between the two, and — if the author has any hopes of being published — a happy ending. But somewhere along the way, the story of how the good arose gets lost in the drama.

In the pharmaceutical industry, amid the glamour of novel mechanisms and blockbuster drugs, manufacturing is often perceived as dull and devoid of science. This misconception can send scientists joining the industry to jobs in the earlier stages of the drug pipeline before they've even considered manufacturing. Scientists with a gift for tackling scale-up issues, an eye for quality or a talent for squeezing efficiency from a highly regulated process may find that manufacturing offers great career opportunities.

"Many of the same skills are required in pharmaceutical manufacturing as in R&D," says Ron Tull, vice-president of human resources for global manufacturing and supply at GlaxoSmithKline (GSK) in Research Triangle Park, North Carolina. "Science helps us understand our product, how we formulate it, how we granulate it, how we blend it, how we coat it. It's a critical ingredient," he says.

Industry experts are seeing changes in the job market for drug manufacturing. Although career opportunities in manufacturing remain stable, their distribution may be shifting. With big drug firms focusing on their core strengths and their ability to cut costs, some companies are relying on contract manufacturing organizations to meet the needs of their pipeline, whereas others continue to hire, says Rich Pennock, regional director of Kelly Scientific Resources. Amgen, for example, had more than 300 manufacturing positions open across the United States in late July. "Everyday R&D is finding new proteins or new molecules to put through trials. It's not just Amgen, it's all over the industry," says Tony Jacobs, associate director for manufacturing staffing at Amgen in Thousand Oaks, California.

Investment in Europe is also growing. Many companies, including Wyeth and Altana Pharma, are establishing facilities in Ireland, one of the world's drug-manufacturing hubs. And the newly built National Biomanufacturing Centre in Liverpool, UK, will offer biotech firms the expertise and facilities to manufacture biopharmaceuticals for early-phase clinical trials. The facility could inject as many as 1,000 jobs into the area over the next 5–10 years. Central and eastern Europe have also been pegged as promising — particularly for generics manufacturing — attracting such companies as GSK, Servier and Sanofi-Aventis.

Luanne Shock: the process must be fast and flexible. Geoffrey Murgatroyd: do you like playing with cars or lawnmowers?

Within a company, manufacturing has two opposing key performance indictors. One calls for efficiency, whereas the other demands the flexibility to react to last-minute marketing forecasts. The challenge is to find the right balance. "We need to make sure that there is enough product, based on marketing forecasts, and that we produce it in a timely, flexible and fast way," says Luanne Shock, executive director of human resources, pharmaceutical operations, at Novartis in Suffern, New York. But from the outside, compliance is key. Like clinical trials (see Nature 442, 480–481; 2006), manufacturing is a highly regulated segment of the drug industry, and those who deviate too far from the script are liabilities.

Broadly speaking, manufacturing delivers products to the market as efficiently as possible. It oversees production, quality control and quality assurance. Team members develop scale-up processes and devise more efficient means of production. Typically, the team gets involved with a drug in the later stages of development, years after its potential was first identified by discovery scientists (see Nature 439, 886–887; 2006.

Production scientists transform raw materials into capsules, tablets and solutions. Scientists can find entry-level positions in the process scale-up area. At Roche's manufacturing facility in Nutley, New Jersey, scientists transform batches weighing less than 10 kilograms to a full batch size, which can hit 900 kilograms.

The position typically demands a degree in pharmacy, chemistry or chemical engineering. But the biotech arena also values life-sciences graduates and even those who have studied food science, because techniques such as fermentation are common to food and pharmaceutical production. Recent college graduates can frequently secure a production position with little or no experience.

Some of the best scientists for production jobs are those who are process oriented and enjoy machinery. "Years and years ago, we used to ask applicants: 'What are your hobbies?'," says Geoffrey Murgatroyd, vice-president of technical operations at Roche. "Anyone who said they liked to play with lawnmowers and cars had a priority because we knew they had an understanding of how machinery worked."

Quality control and assurance are also vital to the industry. Both positions require meticulous analytical scientists with a strong understanding of the regulatory environment. Quality-control scientists work in microbiology or analytical chemistry labs, and, depending on the facility's organization, test raw materials before they are mixed and the products as they come off the line. As new technologies are introduced, product testing will occur on the production line, perhaps changing the role of the quality-control scientist in the future.

Ron Tull: experience helps.

People in quality assurance ensure that drugs are made in a safe and compliant manner, following standard operating procedures and good manufacturing practices. They check batch documentation and may also liaise with the regulatory agencies and review critical paperwork. "People working in our site quality control determine if the product should be released," says Tull. Chemistry, biochemistry, microbiology and biology degrees are popular among this group, and the positions require up to three years' experience. Five years' experience in validation, process scale-up or manufacturing can lead to supervisory roles within manufacturing.

When choosing between candidates, experience and education are important but not always paramount. "The best people are those with an inquisitive mind, who don't accept things at face value, and who keep asking the important questions of why that happened," says Murgatroyd.

Angela Roberts, graduate development manager at AstraZeneca in Macclesfield, UK, agrees: "We need people who will constructively challenge what we do and don't take everything for granted. That's how we get continuous improvement."

Precision also ranks high, says Jay Stout, director of process development at Amgen's Enbrel manufacturing facility in West Greenwich, Rhode Island. "They have to be exacting and really have to know their science."

"Experience isn't required, but it definitely helps," says Tull. "If you have experience working for a pharmaceutical company, make sure you highlight it. You will get attention because you have worked within a regulated industry." Internships (see Nature 439, 504–505; 2006) and graduate-development programmes are great ways to get experience and learn more about different aspects of manufacturing, and employers often hire their interns after graduation, says Stout. Courtney Griffin, now a process validation engineer at GSK's manufacturing facility in Zebulon, North Carolina, spent three summers as an intern at the company during her undergraduate degree. "It's the best way to get your foot in the door," says Griffin.

The way to get ahead is to understand the cutting-edge technologies and processes being applied, such as lean manufacturing, Six Sigma (a data-drive approach to eliminating defects in a process) and process analytical technology, or PAT (see 'A lean sweep'). Some colleges and technical institutes also offer short-degree and certificate programmes in drug manufacturing.

As the pharmaceutical manufacturing industry adjusts to its current challenges, sharp and curious scientists will fare well if they can sniff out the jobs. Those with significantly more experience (upwards of seven years) are in high demand at many large companies. For those reluctant to begin their career in manufacturing, it's important to think strategically. Manufacturing introduces the more regulated side of the industry and can serve as a stepping-stone into other portions of the industry, including discovery or regulatory affairs. A first job in manufacturing could help you create your own fairy tale.

A lean sweep

Cars may seem no more like pharmaceuticals than aeroplanes are like oranges, but from a manufacturing perspective the two are intrinsically tied.

Henry Ford's principles of efficient manufacturing, first put into place by Toyota, lie at the core of today's pharmaceutical manufacturing business. As drug companies face increasing pressure to cut costs yet maintain the safety and quality of their complex products, they are taking lessons from the car industry to become 'lean' manufacturing machines.

"Lean manufacturing is sweeping the industry," says Angela Roberts of AstraZeneca. As a result of this newer trend, senior scientists, in addition to supervising associates, may find themselves re-engineering processes to cut inventory and cycle time, and reduce waste.

Angela Roberts: lean manufacturing takes over.

"We're borrowing from the automotive industry and the electronics industry, which have been challenged to find more efficient means," says Luanne Shock of Novartis.

In 2002, the US Food and Drug Administration (FDA) launched an initiative to bring twenty-first-century regulation to the drug industry. It challenged the industry to better understand and control the manufacturing process by implementing process analytical technology, or PAT, which aims to design and use processes that can consistently ensure a predefined quality at the end of the production line.

"The industry is moving towards online testing," says Geoffrey Murgatroyd of Roche. PAT brings machines and analytical techniques to the production line to give continued readouts of the product's quality. Roche is testing near-infrared spectrophotometry to assess the drug content of capsules as they are made.

"In the next five years we'll see a move towards increasing this process analytical technology — the FDA is pushing it," says Murgatroyd.

H.H.