A NEW KIND OF ENGINEER

THE PHARMACEUTICAL INDUSTRY NEEDED SOMEONE WHO COULD MANAGE THE EXPENSIVE TASK OF DEVELOPING DRUGS. ENTER THE PHARMACEUTICAL ENGINEER

Over the course of the 20th century, the average American's life expectancy went from 47 in 1900 to 77 in 2000. Although a number of factors led to this unprecedented jump, much of the credit belongs to the development of modem medicine. New medicines don't just save and extend lives. They also improve the quality of it, with treatments for everything from asthma and depression to acne and impotence.

But this cornucopia of good health comes at a cost, and a hefty one at that. In 2003 the Tufts Center for the Study of Drug Development pegged the cost of developing a new prescription drug at nearly $900 million. This puts the pharmaceutical industry in an unenviable position in America's healthcare debate. On the one hand, the aging population's increased pharmaceutical use creates greater demand for new medications while pressure to reduce the cost of those medicines increases as well.

To solve these problems the industry looks to a new breed of engineer-the pharmaceutical engineer-to streamline the complex scientific, business, and regulatory processes of bringing a drug to market. The term "pharmaceutical engineering" has a certain appeal, promising lucrative and fulfilling work within the pharmaceutical industry. But ask five different pharmaceutical engineers to define the field and you'll get five different definitions. Some say it applies to the late stages of the drug-making process, and others to issues-like lab design, air handling, and water purification-surrounding the running of pharmaceutical production facilities.

Most engineering educators take a broader perspective on the field. Fernando Muzzio, director of Rutgers University's pharmaceutical engineering program and a professor of chemical and biochemical engineering at the school, says that he sees pharmaceutical engineers' responsibility as the rigorous and systematic use of engineering concepts and methods to scientifically design, develop, and optimize pharmaceutical processes and products. Pharmaceutical engineers know pharmaceutical materials and how products and industry are related. They can also work alongside chemists, biologists, pharmacologists, and regulators.

Henry Wang, director of the pharmaceutical engineering program at the University of Michigan, sees the field in even broader terms. Not only does he consider the development of traditional medicines to be within pharmaceutical engineering's domain but also biomedical devices, biologies like vaccines and gene therapy, and diagnostics. He also cites the emerging 'omics' fields like genomics, proteomics, and personalized medicine as future avenues of pharmaceutical engineering pursuit. "I originally wanted to call it Healthcare Product Engineering," Wang says about the program he helped to start at Michigan, "but that didn't resonate with students and faculty."

But how can a field that's so nebulously defined systematize the complicated drug discovery process? Engineering educators say that because a pharmaceutical engineer has such a broad understanding of process, he or she has a better view of the big picture. "Pharmaceutical engineering really helps people step back and see the industry as a whole," says David Wild, an adjunct professor in Michigan's pharmaceutical engineering program and director of his own scientific computing consulting company, Wild Ideas Consulting.

"There are all these different stages in the drug discovery process, and each stage is dominated by a particular discipline," Wild explains. Historically, the people working in each of these stages-chemistry, biology, pharmacology, engineering, and manufacturing-have tended to do so without necessarily considering the work in subsequent stages. Because of this, scientists spend much time and money working on drug candidates that ultimately fail. According to the Pharmaceutical Research and Manufacturers of America, for every 5,000 potential medicines tested, only five will make it into clinical trials. Of those five, only one will be approved for patient use. In fact, experts attribute as much as 75 percent of the total cost of each marketed drug to the high failure rates of other drug candidates.

Quite often a candidate from one stage in the drug discovery process fails for reasons, such as toxicity or expense of manufacturing, that another stage might have predicted. The intensive clinical trial and FDA approval process-along with complex regulatory, business, and legal issues-can also slow a promising drug candidate's progress to market. And since a new drug makes its developer the majority of its money under patent protection, every delay is costly. Ideally, a pharmaceutical engineer can make the entire process faster, more efficient, and therefore more profitable. "I think the best way of looking at it is that it's all the processes of the pharmaceutical industry viewed from an engineering prospective," Wild says.

Of course, training engineers with such a breadth of knowledge in just one particular industry requires a complex, multifaceted approach. While most educators see interdisciplinary study, cooperation with industry, and knowledge of FDA regulations as essential components in training to become a pharmaceutical engineer, they have different ideas about pharmaceutical engineering education.

PROXIMITY TO PHARMACEUTICALS

Over the past decade, a handful of pharmaceutical engineering programs have popped up across the country. Not surprisingly, most of the universities that have pharmaceutical engineering also have close ties, both geographically and financially, to major drug-making corporations. New Jersey-home to the headquarters of more global pharmaceutical and medical technology companies than any other state or country, for that matter, in the world-boasts pharmaceutical engineering programs at Rutgers University, New Jersey Institute of Technology, and Stevens Institute of Technology. Michigan's Wang says his university's proximity to what was Warner Lambert and is now Pfizer's Ann Arbor facility certainly helped in developing that school's program.

"I think the programs are responding to a perceived need by the pharmaceutical industry to bring in a type of individual who is well-versed in basic engineering principles, but also knowledgeable of regulatory aspects, manufacturing operations found in the pharmaceutical industry and who can communicate with life scientists carrying out the basic research as well as other engineering, architectural, and pharmacy graduates," says Henrik Pedersen, professor in Rutgers pharmaceutical engineering program and chair of the university's chemical and biochemical engineering department.

Although only a decade old, the Rutgers program is one of the oldest in the country. Program director Muzzio credits Carlos Rosas-who, at the time, was Merck's vice president of manufacturing-for conceiving what has become Rutgers' pharmaceutical engineering curriculum. Muzzio says that back in 1994 Rosas took him under his wing and told him, then an assistant professor, that the industry could really use engineers who understood the entire drug development and manufacturing process. So Muzzio began an interdisciplinary program that would give Rutgers' students the option of that specialization. Merck even provided some $50,000 in startup money.

"I used the funding to get the attention of my colleagues," Muzzio says, "and we were able to hire a number of young and eager assistant professors." Since there were basically no programs training potential young faculty in pharmaceutical engineering at the time, the new faculty were sent to do internships in industry.

Even now, professors continue to go back and work with pharmaceutical companies so they can stay abreast of the latest technologies in the field. Muzzio himself recently did an internship with Bristol-Myers Squibb in pharmaceutical operations and statistical design of pharmaceutical operations for a course he plans to teach. "I am learning as much as I am teaching," he says.

The Rutgers program is primarily research driven. Most students are working toward their Ph.D.'s. Undergraduates can take half a dozen courses in pharmaceutical engineering and can do research with professors in the program. Often the graduate students spend some time doing an internship with a pharmaceutical company and then do their doctoral research on a project funded by that company. "This is very much hands-on work," Muzzio explains. "They are immersed in the culture of collaboration."

Unlike those in other pharmaceutical engineering programs, students from Rutgers don't graduate with a pharmaceutical engineering degree. Instead they specialize in pharmaceutical engineering. That specialization complements a degree in a more traditional field like chemical or mechanical engineering. Muzzio takes responsibility for not having a pharmaceutical engineering degree. "We wanted to serve the students by giving them the most flexible degree."

There are currently 15 faculty members in the Rutgers program. Although chemical engineering serves as the program's home base, materials science, mechanical engineering, industrial engineering, and the school of pharmacy are all represented. "Chemical engineering provides a natural foundation for the field of pharmaceutical engineering," Pedersen says. "New methods better able to describe pharmaceutical operations and provide a rational and robust basis for regulatory guidelines are what have driven and will continue to drive the pharmaceutical engineering field to develop its own identity."

At the University of Michigan, the college of engineering and the college of pharmacy jointly administer the pharmaceutical engineering program. Since the program's inception in 2000, 16 students have earned master's degrees in pharmaceutical engineering and a doctoral training program was established last year.

"We want the students to know both the product quality and process efficiency," says Wang, director of Michigan's pharmaceutical engineering program and a professor of chemical and biomedical engineering. So that students get a comprehensive view of the drug development and discovery process, Michigan brings in adjunct faculty from industry and government to teach alongside the school's science and engineering faculty.

The curriculum includes a core course in pharmaceutical engineering that Wang teaches. "Basically, I introduce the students to the industry, what are the engineering issues in drug discovery, and manufacturing," he says. There are also seminar courses with speakers from industry, the FDA, and academia. To get the broad, yet specialized base in pharmaceutical engineering, students also usually take advanced science and advanced engineering statistics, analytical chemistry, and a course in intellectual property from the business school. Most students opt to take a regulatory science course as well, although Wang says in the near future this course will be a requirement for all students in the program.

Research and practical training are also important components of the program. About a third of the students arc pursuing the degree part time while holding down jobs in the industry. Those who don't already have industrial jobs often choose to include internships or co-ops as part of their studies. Wang stresses that whatever project the students work on during these internships, they must be relevant to their training as pharmaceutical engineers. To that end, the students have both an industrial as well as academic adviser.

Jennifer VanRoeyen got her master's from the Michigan program in 2003 and currently works with ZS Associates, a consulting firm specializing in the healthcare industry. She has done two different internships, one with Eli Lilly and Merck on process development and one with Janssen Pharmaceutica, a Belgian subsidiary of Johnson & Johnson, on product development. VanRoeyen says that both experiences gave her an appreciation of all the opportunities the pharmaceutical engineering degree could provide. "As an engineer," she says, "it was a wonderful way to figure where I could fit in at a pharmaceutical company."

Another way that engineers gain specialization in pharmaceutical engineering is through continuing education courses. Michael F. Waxman is one of 30 professors who do outreach teaching in engineering through the University of Wisconsin. Students in the program get continuing education credit from the reputable University of Wisconsin without having to actually go to Wisconsin-which depending upon the season and your interests can be considerably less attractive than where the courses are usually taught. Las Vegas, for instance, is one popular location.

The university offers as many as 30 different short courses in highly specialized aspects of pharmaceutical engineering. Waxman says for two or three days he'll teach an in-depth course on some facet of pharmaceutical engineering to a class of 20 to 150 students, depending upon the subject. Waxman says his students are chemists, biologists, and engineers that work for pharmaceutical engineering companies around the world.

Waxman says continuing education courses like his are attractive to the pharmaceutical industry because they give engineers specific knowledge they need and generally do not learn in school. And because people working in the industry teach the courses, students also keep up to date with the newest technologies and methods and the latest government regulations. "My students leave appreciating the education they get because they know what they need when they're working in industry," Waxman says. "They can use what they've learned the next day."

Educators from Rutgers and Michigan also say their students find the pharmaceutical engineering training to be highly rewarding. "We never have any problems placing our students. They are vigorously recruited by industry," Rutgers' Muzzio says. "I think this is going to be one of the most active growth areas for the profession."

Michigan's Wild echoes this sentiment: "The people who have pharmaceutical experience and the piece of paper to prove it are really going to have the advantage in terms of jobs."

[Sidebar]

THIS LITTLE PILL WENT TO MARKET

By the time a potential drug is taken by a human, it has spent about six-and-a-half years in the discovery/preclinical stage of drug development. During this stage, researchers perform laboratory and animal tests to determine how safe the drug is, how well it works to treat a particular disease, and what type of formulation will be most feasible for the particular compound.

Once completed, the company that made the drug must file an Investigational New Drug Application with the U.S. Food and Drug Administration (FDA) before the drug can advance to clinical trials. For every 5,000 compounds that go through the preclinical stage, only five will advance to human testing.

The human clinical trial phase of the drug development process occurs in three phases. In Phase I the drug is given to a group of 20 to 100 healthy volunteers to study the drug's safety. Researchers also learn how the drug works within the body: how it's absorbed, metabolized, and excreted, as well as how long it is effective. On average, it takes a year and a half to complete this phase.

During the two years of Phase II, clinical trials are conducted on 100 to 500 volunteers with the disease that the drug is being approved to treat. They will take the drug in order to evaluate its effectiveness and to see if there are any side effects.

Phase III clinical trials expand Phase II testing to between 1,000 and 5,000 patients in clinics and hospitals. At this stage, doctors monitor patients closely to confirm the efficacy observed in Phase II and to look for any adverse reactions from long-term use. Phase III can take up to three and a half years.

Once a drug successfully progresses through human clinical trials, its maker will compile all the data generated from the trials and submit it to the FDA in the form of a New Drug Application (NDA). The average NDA weighs in at 100,000 pages. The FDA review and approval process at this stage lasts about a year and a half. For every five drugs that enter human clinical trials only one will get the FDA's nod.

On average, the rigorous drug approval process lasts anywhere from 10 to 15 years, according to the Tufts Center for the Study of Drug Development. The center also estimates that it takes more than $800 million to get to this stage. But even after a drug goes on the market, its maker must periodically submit reports to the FDA. And some drugs must go through additional Phase IV trials to identify any adverse long-term effects. Aftermarket testing can add nearly $100 million in costs, bringing the final tab of drug discovery and development to about $900 million. Still, the hefty costs and high risks haven't kept drug companies from trying to bring new products onto the market. The Pharmaceutical Research and Manufacturers of America says that its member companies spent about $32.1 billion on research and development in 2002.

PERSONAL PHARMACEUTICALS

Ever wonder why a medication that works well on some might have absolutely no effect on others or might even make them violently ill? The answer, scientists say, is locked in our DNA.

Over the last few years, scientific advances like proteomics, DNA microarrays, and the sequencing of the human genome have given researchers insight into how DNA influences the diseases we get and how we respond to different medications. Scientists predict that because of this new genetic perspective on diseases and medications, we'll someday be able to walk into our doctor's office, take a simple genetic test, and get medicine that is tailor-made for us.

Pharmaceutical engineering educators agree that personalized medicine will play a big part in the future of their discipline. And although they say that their programs include faculty and courses in the "omics"-genomics, proteomics, pharmacogenomics-they caution that despite breathless media reports, personalized medicine is still very much in its nascent stages. "We can dream up all these things," says Fernando Muzzio, director of the pharmaceutical engineering program at Rutgers University, "but to make them real we are going to need the same basic engineering fields."

Muzzio adds that pharmaceutical engineers already have plenty of exciting challenges that can impact people's lives and healthcare. "It might not be the sexiest area of work, but it is the area where what we do could reach millions of people tomorrow," he says. "If we can improve the reliability of pediatric formulations, for example, then we can help kids right now. It doesn't matter if we're not being interviewed by Newsweek."

[Author Affiliation]

Bethany Halford is a freelance writer based in Baltimore.