Rules rule

Last year, global spending on prescription drugs exceeded US$600 billion. Topping the sales list were drugs to combat high cholesterol levels, heartburn, schizophrenia and asthma. But regardless of their sales strength, every drug had one thing in common: each had been scrutinized by regulatory-affairs professionals before reaching the pharmacy shelves. Employed by the drug companies and contract research organizations, these experts assemble huge dossiers of data and oversee the mountain of paperwork required by the regulatory agencies that oversee the industry. "Our basic responsibility is to interpret the regulations and guidelines of the different regulatory agencies," says Ken White, vice-president of regulatory affairs at ICOS in Bothell, Washington. Regulatory-affairs professionals are an essential part of the drug-development process, and jobs in the field typically crop up wherever there is healthy investment in R&D. These professionals have a vast scope. They prepare, submit and monitor submissions to regulatory agencies, and get involved in manufacturing, labelling, marketing and post-marketing activities. Increasingly, their involvement begins during the R&D phase, where they help smooth the transition from drug development to clinical trials. Once a company identifies a promising compound, a regulatory-affairs team begins drawing up the plan that will guide the compound through development, clinical trials and onto the shelves. "We work with the scientific team during the preclinical phase to make sure that we have the right data," says Lisa Skeens, vice-president of regulatory affairs at Baxter in Deerfield, Illinois. "We are the liaison between the regulatory authorities and the company, the experts in understanding the regulations and the guidelines. We know through experience what the global regulatory agencies expect." Before starting clinical trials, which involve testing the compound in people, companies must submit an Investigational New Drug (IND) application in the United States, or in Europe apply for a Clinical Trial Authorization. These provide evidence that a compound is both safe and has some beneficial activity — in short, that it merits further investigation (see 'The regulator'). Preparing for the move These applications contain data from preclinical trials, including animal pharmacology and toxicology studies (see Nature441, 544-545; 2006), manufacturing information that ensures the drug can be produced safely and consistently, and detailed clinical protocols for the proposed human studies. Problems at this stage can delay or stop the drug's move into clinical trials. "The agencies provide guidance on how a new drug should be tested, but it's not always black and white. Interpretation makes regulatory affairs interesting and intellectually challenging," says Ann Readman, vice-president of regulatory affairs at AstraZeneca in Alderley Park, Cheshire, UK. The IND is a pivotal point in any compound's move from lab bench to market, but it is only the start of the regulatory-affairs professional's relationship with the drug. "Once you've filed an IND, you've opened yourself up to all kinds of responsibilities," says White. Any new animal studies, or changes to the manufacturing process or clinical protocol, must be submitted to the agency. Also required are annual reports on safety information from the clinical trials, and meetings with the regulatory agencies at key points throughout the studies. Recent safety issues, such as those involved in the TGN1412 clinical trial and the lawsuits surrounding the painkiller Vioxx, have led to heightened awareness and review of the approval process. Some regulatory agencies require industry to take a proactive role and investigate potential safety issues during the product's life cycle using a pre-approved risk-management plan, increasing the amount of work for staff, says Readman. The relationship with a drug may continue until the company stops manufacturing it. "They will work with that compound from the time it emerges from research, through development and post-approval; from birth to death of the product," says Susan Boynton, senior director of regulatory affairs at Amgen in Thousand Oaks, California. Being the link between their company and the regulatory agency, regulatory-affairs professionals have a rare combination of skills. A science degree is usually required. "We are looking first for people who are strong scientists, people with pharmacology, life-sciences and clinical–medical backgrounds," says Skeens. According to a 2002 North American survey, about 60% of them hold at least a master's degree, and nearly 20% have a doctorate. Those with bachelor's degrees and additional training can also make the cut (see 'Learning curve'). But they also must have leadership skills and be impeccable oral and written communicators. That combination of skills is rare in a scientist, says Skeens. Regulatory-affairs specialists need good judgement and the confidence to make predictions about how the regulatory environment is changing. They need a knack for investigating drugs with novel mechanisms of action or new therapeutic areas, such as monoclonal antibodies, years before these will reach the market. Scientists who enjoy strategic planning, working on communications, or having a business perspective also fare well in the profession, Skeens adds. People come from all kinds of backgrounds, says Joseph Scheeren, head of global regulatory affairs at Bayer HealthCare's pharmaceuticals division in West Haven, Connecticut. Some join regulatory affairs immediately after finishing their education; others make internal moves from development or discovery, he says. New recruits can expect to receive a lot of mentoring and coaching during the first two years of their job. Regulatory professionals with experience in a specific therapeutic area are especially appealing to companies that are expanding into new areas. Today's professionals see regulatory affairs as a career that offers continual learning and interaction with scientists and regulators. And with harmonization, changing regulations and the constant expansion of the therapeutic realm, it's never dull. "I've been in the regulatory-affairs area for almost 25 years, but I learn every day," says Scheeren. Word of mouth Scientists and students interested in moving into this area should contact organizations such as the Regulatory Affairs Professionals Society or the Organisation for Professionals in Regulatory Affairs. "These organizations help people get a broader understanding of what regulatory affairs is about," says Boynton, adding that people used to hear about the discipline mostly by word of mouth. "Most of us are very willing to give our time to sell our profession." Job availability in regulatory affairs is linked to the drug-development pipeline and many companies are currently expanding the size of their regulatory-affairs departments. "We are constantly looking for high-calibre candidates," says Boynton, whose department has doubled in size in the past four or five years. "It reflects the large number of new products that we are focusing on. The pipeline is very exciting." The regulatory-affairs profession is still young. It emerged in the 1970s and grew in popularity in the 1980s as the number of INDs skyrocketed. People's perception of it has changed radically over that time. "It's risen in its position in the company in terms of its contribution to the overall business strategy," says Boynton. Readman agrees: "In the old days, the regulatory-affairs function was seen as a negative place to be. They were the people who told you what the rules were." Today, the regulatory-affairs professional works alongside the scientist. "Their data are part of a much bigger picture," Readman says. "Source":[ http://www.nature.com/news/2006/060619/full/nj7096-1022a.html]

---