REGULATORY AFFAIRS
Drug industry relies on those who navigate the ground between development and approval

The pharmaceutical industry is the most regulated of all industries. Think of any drug on the market today to treat a disease, a chronic condition, or even something as mundane--and confounding--as the common cold. No drug would be available without the teams of medical researchers and other specialists who worked to make sure it received Food & Drug Administration approval.

Regulatory affairs professionals are key, but perhaps overlooked, players in drug development. They are the primary communications link between the company and agencies such as FDA, and they are responsible for keeping up with the increasing scope and complexity of regulations both here and abroad.

In the pharmaceutical industry, regulatory affairs professionals have expertise in the legal and regulatory environments, as well as in clinical research protocols. They are the primary interpreters of the laws and regulations for other members of the company's R&D, manufacturing, and compliance staff. Regulatory affairs professionals must have a thorough understanding of the complex set of regulations within which FDA operates: 21 CFR (Code of Federal Regulations), Sections 1 through 1299. They also need to be familiar with regulations promulgated by a whole range of agencies: the Environmental Protection Agency, Federal Trade Commission, Occupational Safety & Health Administration, and Drug Enforcement Administration.

A good regulatory professional must also be aware of the subtleties of regulations worldwide. Keeping up-to-date on regulations is essential in regulatory affairs; changes in regulations can affect the clinical trials process, regulatory strategy, decisions on what kinds of trials are needed, and so forth. New areas evolve as science changes, so time is spent tracking changes in regulations all over the world. The stakes can be high; drug approvals--as well as delays or failures--are featured prominently in the media and can make or break a company.

Although the work emphasizes regulatory knowledge, it's not just for wonks. Scientific training is also valued and helpful. "Employers are looking for people who understand the science that's driving the process," says Sherry Keramidas, executive director of the Regulatory Affairs Professional Society. "Understanding the clinical process and some of the challenges of clinical care helps regulatory affairs professionals understand the clinical trials process and what is or is not possible," she explains.

Bonnie Charpentier, a Ph.D. chemist and vice president of regulatory affairs at Genitope, agrees. "The field of regulatory affairs has become increasingly more science- and issue-based and less rote and bureaucratic, as the speed of the pharmaceutical and biologics development has increased and the science has become more complex. A regulatory professional now spends more time on substantive scientific and medical issues and on planning for the experiments and clinical studies to achieve approval.

"Currently there is a need for regulatory professionals," Charpentier says. "To do the job well requires one to be a generalist, comfortable working across a range of scientific disciplines, and competent in asking questions and defining answers."

SCHOOLS Regulatory Affairs Degree And Certificate Programs While many regulatory professionals in drug companies picked up their regulatory education on the job, there are colleges and universities that offer degrees or certificates in regulatory affairs and other related subjects. Among U.S. universities, only the University of Rhode Island offers a Ph.D. in regulatory affairs, through its Department of Applied Pharmaceutical Sciences. The program enables students to specialize in various aspects of drug development and drug regulations pertaining to the development process. Several universities and colleges have master's programs, including those listed here: Temple University offers an M.S. in quality assurance/regulatory affairs. Long Island University's Arnold & Marie Schwartz College of Pharmacy & Health Sciences offers an M.S. in drug regulatory affairs. Massachusetts College of Pharmacy & Health Sciences offers an M.S. in drug regulatory affairs and health policy. San Diego State University's College of Sciences created an M.S. in regulatory affairs within its Center for Bio/Pharmaceutical & Biodevice Development. The University of Southern California launched an M.S. in regulatory science degree program in 2001. Other institutions do not have degree programs but offer certificates in regulatory affairs. For example, the University of California, San Diego, offers a variety of certificate programs through its post-bachelor's education program called The Extension. And the University of Washington offers a nine-month program in biomedical regulatory affairs.

ABOUT A YEAR and a half ago, Rebecca Braatz transferred to a regulatory affairs position at Roxane Laboratories, a subsidiary of Boehringer Ingelheim located in Columbus, Ohio, where she prepares and submits Abbreviated New Drug Applications (ANDAs) to FDA. Braatz has a B.S. in chemistry and 15 years of experience at the bench. After working in analytical development for six years at Roxane, Braatz explains why she chose to move into regulatory affairs: "I knew that I enjoyed the pharmaceutical industry and wanted to stay with it if possible. I chose regulatory affairs because it involves a lot of writing, which I enjoy, and it appeared to be a logical next step after working in analytical development. I can continue to use my chemistry knowledge in putting together the chemistry, manufacturing, and controls [CMC] sections of the applications. My knowledge of the company and the pharmaceutical production process has grown immensely, and it's been fun to follow projects from the beginning all the way to launch."

At the senior level, regulatory affairs professionals should be able to look at the big picture and think strategically. "They should understand how the regulatory process affects the bottom line," Keramidas says. "They need to be able to evaluate risk: what you can or cannot do and what the consequences are for the company and the regulatory process."

Regulatory affairs professionals need to be highly organized. Attention to detail is critical because FDA approval depends on the data submitted as part of the New Drug Application (NDA). Every new drug since 1938 has been the subject of an approved NDA prior to U.S. commercialization.

Orin Tempkin, who works in the CMC regulatory group at Novartis, agrees: "The CMC documentation we provide to FDA and other global health authorities is highly detailed, with the amount of detail gradually increasing as you go from clinical trials to market. The content of regulatory documentation must be carefully considered and constructed to make sure it fulfills the demands of published regulatory guidances, giving sufficient information but not excessive or unnecessary details that might provide for too little flexibility."

Regulatory affairs professionals need strong communication and facilitation skills because drug development is a team effort. "I interact with many other groups in the company to get documents needed, such as batch records, production equipment information, packaging specifications, and technical reports," Braatz says. "This interaction has been a very valuable learning experience. While working in regulatory affairs, my knowledge of the company and the pharmaceutical production process has grown immensely."

Communication and organizational skills are also extremely important in dealing with government agencies. Antony Wright, an associate technical director at Strem Chemicals, says: "FDA has a huge job. It's important to help them as much as possible. The key is to have an open attitude toward regulatory compliance."

Tempkin considers interacting with FDA staff to be an exciting part of the work. "A graduate education in chemistry is excellent training for successfully interacting with FDA, because you have to make strong scientific arguments to support your company's products, as well as answer challenging questions that arise from the review of regulatory dossiers. It reminds me of defending a Ph.D. thesis."

THE DRUG DEVELOPMENT process is carefully defined by FDA. The first step is preclinical studies, which test a drug on animals to determine possible toxic effects. Clinical trials, which follow if warranted, are conducted in three stages to gather data for the NDA. FDA then conducts a regulatory review based on the data in the NDA. A final step is postmarketing surveillance, which monitors and evaluates a drug's safety after it's approved and marketed, especially when a company receives reports of adverse drug reactions.

Regulatory affairs professionals perform a wide range of activities in the drug development process, which vary depending on the product line and the size of the company. As Keramidas explains, "Many [professionals] are involved in the process from actual development--bench research--all the way through the life cycle of the product. Some will have been bench scientists or clinicians and may get involved in different processes. If the company is a start-up, they're involved in both the research and the regulatory process."

Because Strem Chemicals is a small company, Wright does all of the regulatory work for its active pharmaceuticals business, serves as the quality control manager for pharmaceuticals, and contributes to Strem's nonpharmaceutical business.

In contrast, global companies have a more extensive approach to regulatory affairs. For example, Tom Scalora, a regulatory affairs manager for GlaxoSmithKline, focuses on over-the-counter drugs. GlaxoSmithKline has a local regulatory affairs group, which deals primarily with the local geographical market; an international group, which handles general international issues; and a central group, which oversees the entire global picture. Scalora personally handles North American regulatory affairs for the oral health care product line; his associates do the same for other products.

Scalora interacts with the international and central groups almost daily because his product line is distributed worldwide. He also performs all of the research and interpretation of the regulations for new oral care products and claims. Scalora is familiar with regulations in other countries, but the local groups in those countries are the experts for their regions.

Keramidas also notes that regulatory affairs personnel are becoming involved in the laboratory, asking what it's going to take to test and get that product approved, and looking ahead to the regulatory part of the process. They may consult with other departments and get involved in the planning of clinical trials. Regulatory affairs staff are also beginning to influence the structure of data collection.

As a product goes through the review process, regulatory affairs professionals are looking at requirements for manufacturing, packaging, and advertising. Manufacturing gets involved with quality assurance and quality control; packaging, labeling, and advertising will also interface with manufacturing. There are stringent regulations everywhere that govern these spheres. Regulatory affairs personnel work with distribution and make sure the processes meet regulatory requirements. As the product is used, regulatory affairs is involved in reporting any adverse effects from a drug to FDA.

NETWORKING AND career transitions seem to be the most common way to go into regulatory affairs. The scientists interviewed for this article didn't start out their careers in this field. Wright, for example, found a second career at Strem Chemicals after retiring from Dow Corning.

Novartis' Tempkin received a Ph.D. in organic chemistry and moved to industry as a process research chemist. After a postdoc at Merck, he started at Sandoz Pharmaceuticals, and after two years in the process research labs at Sandoz, he began looking for a position outside the laboratory. After Sandoz and Ciba Geigy merged to form Novartis, he learned of an opportunity through his network in the R&D quality assurance group, which was responsible for the quality and Good Manufacturing Practice compliance of investigational drug substances and drug products used in clinical trials. In this position, he became acquainted with several colleagues in the CMC regulatory affairs group, and his interest started to grow, particularly with the idea of using his scientific background to interact with FDA to get new drugs approved. Internal networking and cultivating internal contacts helped him make the transition to the CMC regulatory group.

Jean-Paul Gleeson, an associate scientist in the pharmacokinetics, dynamics, and metabolism group at Agouron Pharmaceuticals, a Pfizer subsidiary in San Diego, received a bachelor's degree in general chemistry. Gleeson didn't decide to go into pharmaceuticals until he did an internship at Agouron. The internship and another class in pharmaceutical sciences sparked his interest in regulatory affairs. Experts visited the class from various pharmaceutical and biotech companies to talk about scientific careers, and regulatory affairs sounded most interesting.

Currently, his job includes characterizing the pharmacokinetic compounds of Pfizer candidate compounds, which requires him to write reports for project summaries. The summaries are eventually used to write applications for FDA approval or to update FDA on the company's current knowledge of a drug's safety in the investigator's brochure.

Gleeson's advice to anyone interested in regulatory affairs is "to get experience in small companies. This opens up the door more than an education (such as a master's degree or a certificate in regulatory affairs) does. The most important thing to have is a good network to help you succeed in getting the right positions, and a good general knowledge of the regulations and guidance documents that pharmaceutical companies must follow."

Gleeson also recommends pursuing regulatory affairs certification (RAC) through the Regulatory Affairs Professional Society, which has been awarding certification since 1990. Exams are given annually in November for the initial certification; recertification depends on continuing education and professional development. Candidates must have a bachelor's or equivalent plus three years of regulatory experience.

RAPS administers both a U.S. and a European Union certification exam. The EU exam was given for the first time in November 2001. Both exams cover the specific region's regulations for biotechnology and health care products including pharmaceuticals, medical devices, biologics, and cosmetics. RAPS Executive Director Keramidas says most of the members are very actively engaged in the profession, part of the basis for recertification.

HOW DOES regulatory affairs certification enhance someone's employment prospects? "We find at the newer professional to midprofessional level there is a definite influence on salaries," Keramidas says. Certified professionals "earn anywhere from 5 to 15% more than their peers. We're also finding a very large proportion of senior professionals who are certified. The impact on those salaries is minimal because at that level, other factors are involved in salary calculations. In addition, many companies--both large and small to midsize--are now beginning to indicate that RAC is a desirable qualification."

Charpentier concurs, "When we're hiring a regulatory person, we look at a great many factors. Earning the RAC may indicate that a relatively less experienced person has gone to the trouble to get training and certification, and is therefore viewed favorably."

Braatz's advice for anyone considering a transition into regulatory affairs is to become educated about the field. "Get to know someone in the regulatory group and start asking questions. I would also suggest joining a professional society, like RAPS. It offers many short courses and conferences, ranging from the beginner level to experienced, and its monthly publication and website are very informative." Braatz is considering pursuing her M.S. in regulatory affairs through Temple University. (See page 78 for more information about regulatory affairs degree and certificate programs.)

"My experience in technical writing, computer skills, broad knowledge of chemistry, process engineering, and the ability to educate myself by reading regulatory material has made the difference," Wright says. "I really enjoy Strem, the challenge of doing everything by the book but still being efficient, and working with many contacts outside the company."

Industry experience in regulatory affairs is a valuable commodity. If you're looking for a career transition and are interested in public service, you could transition to a government agency such as FDA to review drug applications (see page 58). However, FDA is experiencing some growing pains and faces some administrative challenges in the near future. Among them, the agency has experienced tremendous growth with the passage of bioterrorism legislation, providing it with 800 additional employees, and it received permission to hire another 450 staffers under the Prescription Drug User Fee Act.

"Most FDA reviewers are overloaded already," Charpentier says. "If additional work is to be done to support antibioterrorism activities, it will require additional personnel and careful management of focus and resources. I don't know how these efforts will affect the drug approval process. I share the concerns of many that the advances made in terms of speed of approvals should not be allowed to lose ground." At a confirmation hearing in October, FDA Commissioner Mark McClellan acknowledged that reducing high reviewer attrition rates is a top priority.

Another area of transition is the clinical research organization (CRO). According to the Association of Clinical Research Organizations, there are literally hundreds of CROs worldwide employing a workforce of nearly 100,000 professionals. CROs provide independent product development services primarily for the pharmaceutical, biotechnology, and medical device industries. Companies in these industries often outsource product development services to CROs in order to manage the product development process more efficiently and cost-effectively. In 1992, estimated CRO market size was $1 billion; today that number is over $6 billion and growing.

DRUG DEVELOPMENT is long, risky, and expensive, and those characteristics mean regulatory affairs personnel have their work cut out for them. Agouron's Gleeson notes: "It is becoming harder to get a drug approved than it was in the 1990s, when the government was more concerned with not being able to treat a disease than they were regarding the safety of pharmaceuticals. This creates opportunities for new regulatory affairs professionals and also challenges to get drugs approved."

"The challenges occurring in regulatory affairs are largely the same as those in the pharmaceutical and biologics fields in general," Charpentier says. "Advances in genomics and proteomics are examples of knowledge and expectations expanding quickly. Regulatory professionals must be able to keep up with scientific advances in order to do their jobs effectively," she adds. "Regulations and guidelines lag behind scientific advances; a good regulatory person can interpret existing regulations as they apply to new developments and define what questions need to be resolved with regulatory authorities when the regulations are not clear."

Regulatory affairs provides an in-depth overview of the full spectrum of drug development, from clinical trials to marketing to postapproval activities. As members of the drug development team, regulatory affairs professionals play a very important role in new drug approvals.

"Regulatory affairs is becoming increasingly influential in the overall drug development process and increasingly populated by highly trained scientists and medical professionals," Charpentier observes. "Years ago, regulatory affairs was often just a place where paperwork was done. There is still a lot of paperwork, although much of it is now in electronic format, but science and strategy now take precedence."

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