Michelle Hoffman, editorial director of Pharmaceutical Technology.

Michelle Hoffman

1977—Orlando Bloom was born, and Elvis Presley died. Jacques Chirac was elected mayor of Paris, Indira Gandhi resigned her post as India's prime minister, and Jimmy Carter pardoned most of the Vietnam draft evaders. It was the year in which 

 won the Academy Award for Best Picture, 

 debuted, Jay Leno appeared for the first time on Johnny Carson's "Tonight Show," and the last episode of "The Mary Tyler Moore Show"aired. The Oakland Raiders beat the Minnesota Vikings, 32-14 in Superbowl XI, and the Concorde began regular passenger service between New York and Europe. Studio 54 opened its doors for the first time. That year, before Rosalyn Yalow shared the Nobel Prize in Physiology or Medicine, and after 

 premiered on TV, the first issue of this magazine was published. 

1977 was a time when the medical research community felt especially confident about its ability to vanquish infectious disease; the United Nations had declared that smallpox had been officially eradicated worldwide one year prior. The emergence of HIV and AIDS, which would shake that confidence, was, of course, still a few years away. The war on cancer raged, and a new technology on the horizon filled many in the drug-development field with a great sense of possibility. Monoclonal antibodies had been discovered a couple of years earlier, and researchers set out almost immediately to demonstrate how these highly specific molecules might be used to attack cancer cells with near-surgical precision. Most of those efforts were met with disappointment, and by the 1990s, many had become skeptical that mono-clonal antibodies would provide the much hoped for "magic bullet." Had that technology panned out, the revolution in biopharmaceutical manufacturing may have happened a bit earlier than it did—and more publicly. But as it was, the genetic revolution snuck up on the industry. 

In 1974, investigators learned how to splice together unrelated pieces of DNA, but because they were working with lowly bacteria, the revolutionary nature of their accomplishment wasn't immediately apparent. Perhaps, more people took notice in 1976 with the incorporation of Genetech, the world's first biotechnology company, which was founded to commercialize the pharmaceutical inventions that came out of those obscure splicing experiments. We are just now—30 years later—seeing the fruits of the genetic revolution. In 2006, two biological products entered the world's top 10 bestseller list for the first time. 

To accommodate these new technologies, new manufacturing procedures are being invented. And with those, come new regulations. As we speak, the US Food and Drug Administration is grappling with the appropriate ways to monitor biopharmaceuticals and the processes used to make them, particularly in the case of generic biologicals. 

None of which is to say that the formulation and manufacture of small-molecule drugs has remained stagnant. Far from it. Drug makers now have at their disposal an increased arsenal of tools and techniques with which to address century-old problems of solubility, bioavailability, and drug delivery, to name a few. The methods for grinding, drying, analyzing, and purifying compounds of all stripes have become increasingly efficient—as are the methods for discovering these compounds. Overall, these 30 years have been remarkable for the changes that have come about and the ideas drug developers have for the industry's direction in the future. 

But the pharmaceutical industry isn't the only one to evolve these past three decades. The business of publishing has also undergone revolutionary change. I refer, of course, to the invention and widespread use of the Internet. While print hasn't disappeared (yet), the Internet has opened up unimagined possibilities for sharing information. So we at 

, as part of a community of dynamic inventors, are also innovating. This month, we unveil our redesigned website (

). You can see the fruits of our labors (and imaginations) unfold in the coming months as we increase and improve our interactive offerings and make the website an invaluable companion to the magazine. So, here's to you and us and sharing our mutual quest for innovation and excellence over the next 30 years.

Articles

Thirty years ago, the world was a very different place; so was the pharma industry.

Standing the Test of Time

The US Food and Drug Administration has always found itself with a nearly impossible balancing act. On one hand, it is responsible for the safety and efficacy of drugs released on the market—a process that requires a lot of care and no small amount of time. On the other hand, with so many promising new drugs in the pipeline, the agency is under pressure to speed approvals to get much needed, sometimes desperately needed, drugs to market as quickly as possible. What to do? Expediting drugs to market suggests rushing some safety tests. Performing time-consuming and sometimes irrelevant analyses of drug safety might delay drugs from getting to the people who don't have time to wait. 

Critics of FDA feel the agency's budget has been imbalanced, historically favoring speed to market over safety. In a 2005 policy statement, the Consumers Union, publisher of 

"Tens of thousands of people have died and been injured under the current system, which emphasizes getting drugs to market, while giving short shrift to determining the safety of those drugs once they are in the marketplace and in use by millions of Americans".

As this issue went to press, the Senate sought to redress that imbalance. In approved legislation, the Senate increased funds to FDA for postapproval surveillance of drugs. The additional funds are to be paid by companies that "use" FDA—that is, pharmaceutical and biotech companies submitting drugs for marketing approval. In addition to improving the agency's premarket process for assessing drug safety and efficacy, the  Prescription Drug User Fee Act (PDUFA) provides funds to track the safety of drugs once they are released. According to a May 9, 2007 report in the 

, the bill doubles the maximum civil fine to $2 million for any drug maker that violates an FDA safety plan. FDA could also order changes in a label or require additional clinical trials for a drug that's already on the market. (Under the current system, clinical testing is not resumed after the drug is released.) Furthermore, the bill requires the government to establish a public database of clinical trials and their results, making it "difficult for drug companies to hide evidence of safety problems," which, noted the 

 report, some lawmakers felt had been the case in the past. 

The bill has received widespread approval among representatives of the pharmaceutical industry. In a statement issued the day the bill was passed, Billy Tauzin, president and CEO of Pharmaceutical Research and Manufacturers of America (PhRMA), said, "In general, the legislation passed by the Senate will preserve—and even strengthen—the FDA's ability to do its job."  

I am delighted that postapproval surveillance is coming into equilibrium with preapproval surveillance. But oversight can be more rigorous still. Specifically, I am concerned about the drug's introduction to the public. I am concerned about direct-to-consumer advertising. The PDUFA bill that just gained approval in the Senate sets aside funds for FDA to review these ads and empowers the agency to impose fines for false or misleading commercials. But I wish it had gone further. 

Consumers Union conducted a survey of direct-to-provider and direct-to-consumer ads produced between January 1997 and November 2002, and its findings, summarized in the 2005 report, included "a broad and disconcerting range of misleading messages." The report went on to say that in spite of an "upturn in strong warning letters," for which the Union congratulated FDA, nothing had changed in the "type of abuses detected" in 2005. 

 A widely cited statistic holds that two-thirds of all drug withdrawals occur within the first three years of release, so several organizations—Consumers Union and the Institute of Medicine among them—have suggested imposing a two- or three-year moratorium on these ads following a drug's release. That would give drug manufacturers and regulators time to gather accurate safety data about the drug and, said Consumers Union, "result in a major reduction in the use of drugs eventually found unacceptably risky."  

With Senate approval, PDUFA will now go to the House for a vote—expected in July. Perhaps between now and then, US representatives will impose the advertising moratorium and make the bill one that truly protects the public from unsafe drug claims as well as unsafe drugs.  

Perhaps Congress can help FDA meet its multiple oversight demands.