Concern about pharmaceuticals in our water supply has been in the public consciousness for a few years now. In 2009, the Environmental Protection Agency found traces of various drugs in fish caught in rivers that receive effluent from wastewater-treatment plants. The drugs were believed to come from doses that people had excreted or flushed down the toilet. In response, FDA updated its guidelines for disposing of drugs. New research, however, shows another potential source of drugs in our waterways.

French scientists investigated fish called wild gudgeon that lived upstream and downstream of a steroid-manufacturing facility owned by sanofi. About 60% of the fish downstream of the facility had both male and female sexual characteristics, as opposed to 5% of the population upstream. Researchers identified pollutants such as diuretics and anti-inflammatory agents in the river. The fish’s abnormalities could prevent them from breeding and also signal problems in other species.

“People think drug release is regulated, but it’s not,” said Joakim Larsson, a pharmacologist at the University of Gothenburg in Sweden, to Nature. But this lack of oversight may end: the European Commission is now considering whether to set limits on common drugs (e.g., ibuprofen and the contraceptive ethinylestradiol) in waterways.

Setting limits might prove difficult, however. Scientists have not yet determined safe limits for many pharmaceuticals in the aquatic environment, or how widespread the problem is, according to Susan Jobling, an aquatic ecotoxicologist at Brunel University in London who spoke to Nature.

The French researchers’ findings certainly are alarming, but regulators won’t have a solid basis for any decisions until more information comes to light. I’m encouraged that sanofi is cooperating with regulatory agencies, researchers, and ecological associations to investigate the scope and root of the problem. In the meantime, the pharmaceutical industry would do well to keep this story in mind, and perhaps review whether it can reduce the potential risks of its waste-disposal procedures.

Also see my previous posts about pharmaceuticals in water:

“Water without Side Effects”

“Hope for Bipolar Fish”

Several developments in 2004, particularly concerns about Merck’s arthritis treatment Vioxx, led patients and lawmakers to question the safety of marketed drugs. FDA received a lot of public criticism for not being vigilant enough, and the agency responded by re-evaluating its practices.

“The FDA’s shift in recent years to an increasingly cautious, risk-averse posture toward new drug approvals has had the unintended consequence of reducing investment in life-sciences innovation due to the significant additional time, cost, and uncertainty it has added to the drug-development process,” said Leff in written testimony to the US House of Representatives’s Energy and Commerce Committee. Medical research “is exploding with potential,” he added, but FDA’s new caution makes it hard for investors to earn returns.

But drug-approval figures seem to undercut Leff’s argument. In testimony before the same House committee, Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, cited a trend toward greater first-cycle approvals for priority new molecular entities (NMEs). The average first-cycle approval rate for priority NMEs has increased from 46% in 1992 to 68% to date, she said. First-cycle approval rates for standard NMEs have also increased from an average of 30% to 38%, according to Woodcock.

Woodcock also countered claims that FDA approves drugs more slowly than EMA. “Of the 35 cancer drugs approved by FDA or the EMA from October 2003 to December 2010, FDA approved 32—in an average time of 261 days,” she said, citing an article in Health Affairs. In contrast, “EMA approved only 26 of these products, and its average time was 373 days.”

Drugmakers’ lack of approved new drugs might have many causes. Now that the low-hanging fruit has been picked, drug discovery itself has become harder. Although FDA is a fair target for criticism, I don’t think the agency can be blamed for quashing innovation. With appropriate funding, scientific expertise, and federal help, drugmakers should be able to develop the new products that keep them and their patients healthy.

The cable is organized by region, and many of the drug and biologic facilities that it mentions are located in Europe. Among them are Baxter’s (Deerfield, IL) immune globulin intravenous facility in Vienna, GlaxoSmithKline’s (London) pertussis-vaccine facilities in Belgium, Novo Nordisk’s (Bagsvaerd, Denmark) insulin facility in Denmark, and Genzyme’s (Cambridge, MA) fill–finish plant in Waterford, Ireland. Contract manufacturers also are represented by Vetter’s Ravensburg, Germany, facility.

Chemical suppliers also make an appearance. BASF’s Ludwigshafen, Germany, plant is called the “world’s largest integrated chemical complex.” And the cable asserts that Siemens’s Erlangen, Germany, location provides “essentially irreplaceable production of key chemicals.”

The leaked cable contains no revelations. The mentions of the Siemens and BASF facilities are no surprise, nor is it a shock to know that Hoffman–LaRoche’s (Basel) headquarters is an important supplier of Tamiflu. Any interested journalist or college student could have found this information—which is public, after all—through a bit of research. I’d argue that the leaked cable does no significant harm, nor does it aid any would-be terrorist.

The cables that revealed diplomats’ candid assessments of international leaders could complicate relations between the US and other countries. But the leaked CFDI list actually could benefit the pharmaceutical and biopharmaceutical industries—and the world at large—if it prompts the cited companies to take steps to secure their facilities.

First, Novartis agreed to pay as much as $152.5 million to eligible class members, including current and former sales representatives and entry-level managers. The plaintiffs apparently are satisfied with the settlement, which allows “full compensation” for the women, thus “ensuring that every woman who worked at Novartis over the past eight years has been compensated fairly,” according to David Sanford, the plaintiffs’ lead lawyer, in a press statement.

Even better, Novartis agreed to spend $22.5 million on programs designed to ensure fair treatment of all members of the company’s sales force. For example, Novartis will revise its sexual-harassment policy and training to stress that it will not tolerate inappropriate behavior or comments. The company also will work to ensure that employees can raise concerns safely and that the complaints are addressed promptly. Novartis also will revise its performance-management process, which could help prevent raises and promotions from being withheld on the basis of sex.

Perhaps the most important part of the agreement is the company’s pledge to retain an external specialist who will identify and remedy, with recommendations from the plantiffs’ lawyers, unjustified gender disparities. If the specialist is sufficiently motivated and perceptive, his work could go a long way toward closing the gender gap that apparently exists at the company. This arrangement could be a model for the pharmaceutical industry, which, like other industries, still suffers from discrepancies in pay and opportunity that fall along gender lines.

I suggest that Novartis’s new specialist investigate whether women are equally represented in the company’s management positions. It still seems to me that too few women are promoted to these types of jobs, and companies would reap various benefits from having more women managers.

The settlement between Novartis and the plaintiffs promises to help reduce gender inequality at the company. The outside specialist’s oversight in particular gives me hope that Novartis will be held to account if its policies result in discrimination. The pharmaceutical industry as a whole should take note of this settlement and remember the still unresolved problem of gender-based inequality.

The suit was brought by Novartis employees whose primary responsibility is to visit physicians’ offices, drop off drug samples, and deliver scripted messages about the company’s products. Echoing the opinion of much of the pharmaceutical industry, Novartis argued that these workers are outside salespersons and therefore exempt from overtime pay under federal and state law.

The case finally reached the US Court of Appeals for the Second Circuit, which rejected Novartis’s reasoning. The decision might have been influenced by the US Department of Labor, which took the unusual step of filing an amicus appeal brief in support of the sales reps. This decision likely will affect the entire pharmaceutical industry, which faces several similar lawsuits filed by sales reps seeking overtime pay.

At first glance, the decision seems like good news for pharmaceutical sales reps. But the obligation to pay overtime might become another excuse for drug companies to cut their sales forces. In response to the recession, pharmaceutical manufacturers have laid off thousands of reps as a cost-cutting measure. Even without the recession, reps have been on shaky ground as physicians become increasingly unwilling to meet with them. As a result, companies have sought alternative ways of reaching doctors such as e-detailing.

I’m happy to see the Department of Labor and the Second Circuit protect sales reps’ right to fair compensation. On the other hand, I still fear for the reps’ jobs under the current market conditions. Maybe new blockbusters would be the best cure for these workers’ job insecurity.

Scientists previously have observed active pharmaceutical ingredients (APIs) in our water supply, thus spurring calls for an investigation. The US Geological Survey (USGS) now has conducted the first study in the United States that assesses pharmaceutical manufacturing facilities as a potential source of pharmaceuticals in the environment.

The group discovered that effluent from two wastewater-treatment plants in New York that receive more than 20% of their wastewater from pharmaceutical facilities had concentrations of pharmaceuticals that were 10 to 1000 times higher than outflows from 24 plants nationwide that do not receive wastewater from pharmaceutical manufacturers. Among other APIs, USGS found 3800 ppb of the muscle relaxant metaxalone and 1700 ppb of the analgesic oxycodone in wastewater-treatment plants’ effluent.

One goal of the study was to help officials develop effective water-management practices. Indeed, current practices may be insufficient. A recent European study found that treatment failed to remove the majority of pharmaceuticals from incoming wastewater, and these drugs were still present in the river waters receiving the treated water. On the positive side, European researchers found that single pharmaceuticals in river waters posed no significant risks, probably because they were highly diluted. But pharmaceuticals often are present as mixtures that could have greater, unknown toxic effects on ecosystems.

USGS has done us all a favor by quantifying the levels of APIs in the effluent from treatment plants, but this should be the first step in a longer process. We need to gain a clearer understanding of APIs’ potential effects on ecosystems so that we can set limits on these chemicals. Ultimately, we must use data from USGS and future studies to find better ways of removing APIs from wastewater. I think that these steps are crucial to safeguarding our health and to protecting our environment.

On Friday, the US Treasury released details about its Therapeutic Discovery Project Program, which was created by the Affordable Care Act to support small pharmaceutical and biopharmaceutical companies’ research efforts. The program’s goals are to promote the development of new therapies, create US jobs, and increase US firms’ competitiveness.

Companies with 250 employees or fewer can apply for tax credits worth as much as 50% of the cost of qualifying research investments. Each company could earn a maximum credit of $5 million. To provide an immediate boost to the industry, the credit will cover research investments made in 2009 and 2010. To startup firms that have not yet become profitable and thus cannot take advantage of a tax credit, the Treasury will offer grants.

On Friday, the Internal Revenue Service published guidance that explains how firms can apply to have their research projects certified as eligible for the credit. Projects must show “significant potential to produce new therapies, address unmet medical needs, reduce the long-term growth of healthcare costs, and advance the goal of curing cancer within the next 30 years,” according to a statement from the US Treasury. The application period begins on June 21, 2010 and lasts through July 21, 2010.

It’s heartening to see the US government try to encourage the development of new treatments, especially in a difficult economy. With luck, the industry’s pipelines and the country’s patients will both benefit. The Therapeutic Discovery Project Program should remind industry of just how valuable R&D scientists are, and I hope it encourages small firms to hire more of them. The program might just put a spring back in the step of these researchers.

EPA recently listed pharmaceuticals such as erythromycin and estradiol as candidates for regulation in drinking water. It also will look for 125 pharmaceuticals or related chemicals at 50 water-treatment plants. The results of the research could lead EPA to draft drinking-water standards. EPA had not previously included pharmaceuticals on its list of candidates, but now recognizes their potential adverse health effects.

Many unused drugs get into the water supply after they are flushed down the toilet. But the US Food and Drug Administration wants to develop programs to return unused drugs, thus preventing them from entering the water supply. Many communities created drug-return programs this year. In these programs, the drugs usually are incinerated to destroy their active ingredients. For the time being, FDA has updated its recommendations about which medicines should be flushed and how.

I’m glad that EPA is beginning to monitor pharmaceuticals in our water. The agency’s new study will help us understand the magnitude of the problem. I think FDA’s goal of universal drug-return programs is commendable because it would all but eliminate concerns about pharmaceutical contamination of drinking water. It’s reassuring to see public officials take steps to address potential hazards such as this one. Maybe 2010 will sharpen our government’s focus on the public’s well being. I’ll ring in the new year with a drink to your health!

At first blush, it looks like drugmakers took a beating. The New York Times said that the drug industry receives “harsh treatment” in the bill. In June 2009, President Obama and the Pharmaceutical Research and Manufacturers of America (PhRMA) agreed that the industry would provide $80 billion in rebates and discounts on branded pharmaceuticals over 10 years. The House bill would require drugmakers to provide another $60 billion in rebates over the same period, making a total of $140 billion in concessions.

These rebates might have been what Ken Johnson, PhRMA’s senior vice-president, had in mind when he said in a press release that the House bill would kill tens of thousands of jobs in the pharmaceutical industry. Yet the additional rebates might not be included in the healthcare-reform bill that the Senate eventually passes.

The House bill also would enable the government to negotiate the prices that Medicare pays for drugs, a policy that the industry has so far opposed. On the other hand, the bill would not allow Medicare to create a formulary. This omission essentially vitiates Medicare’s price-negotiating power, said Steven D. Findlay, senior health-policy analyst of Consumers Union, in the New York Times article.

Ultimately, I think it’s too soon to draw conclusions about what healthcare-reform legislation will mean for the pharmaceutical industry. The Senate has yet to pass its own version of the bill. The Senate bill might not, for example, require the additional rebates from the industry that the House bill does. It might, as the House bill does, give biologics protection from generic competition for 12 years. And after the Senate passes its bill, it will have to be reconciled with the House bill.

Despite its initial alarm, PhRMA seems determined to withhold its judgment. “This is a three-act play, and a good critic doesn’t write a review after the opening scenes,” said Johnson in the press release. Time will tell what shape the final legislation takes. It is at least conceivable that the industry could gain from healthcare reform. The law that Obama finally signs could expand the industry’s market, increase drug sales, and provide incentives for innovation.

That’s why news from Ecuador made me do a doubletake.

Last Monday, Ecuadorean President Rafael Correa gave local officials the power to issue compulsory licenses that enable Ecuadorean companies to bypass patents and produce inexpensive versions of various drugs. Correa’s decree did not specify which, or even how many, drugs’ patents could be bypassed. The licenses, issued according to the World Trade Organization’s rules, are intended to expand access to medications and improve public health.

To my surprise, Pfizer (New York), GlaxoSmithKline (GSK, London), Bayer (Leverkusen, Germany), and others reacted to the announcement with equanimity. In a statement, these and several other companies said, “We accept the democratic decision … to use this extraordinary legal measure, observing the rights and responsibilities” laid out in international law. “No legal right of any kind can take precedence over the interests of public health,” they added.

This reaction is 180° from the opposition that Brazil and Thailand faced in 2007 when they used this tactic. The International Federation of Pharmaceutical Manufacturers and Associations criticized Brazil for not collaborating with Merck (Whitehouse Station, NJ) before its government issued a compulsory license for the AIDS treatment Efavirenz. After Thailand issued a compulsory license for Abbott’s (Abbott Park, IL) Kaletra, the company said it would no longer register new drugs for sale in that country.

I could not find statements responding to Correa’s directive on these companies’ websites and I don’t know why they reacted differently than Merck and Abbott did in 2007. Maybe Pfizer, GSK, Bayer, and the other companies coordinated their response to improve their public images. Or maybe their statement reflects a changed attitude about the limits and ethics of patent protection.

Whatever their motivation, these companies’ endorsement of compulsory licenses will likely set a precedent that makes other drugmakers more willing to accept this legal measure. Compulsory licensing is sanctioned and regulated by international governments and trade organizations. I think it can be a valuable tool that saves patients’ lives, and I’m heartened by the thought that Big Pharma might be more tolerant of this measure in the future.