Poor Marie Antoinette got a bad, and likely undeserved rap for the phrase "let them eat cake." which she may not even have said. (Credit to Sofia Coppolla for presenting a more balanced view of the princess in her 2006 film and to Stefan Zweig for one of the first balanced biographies). In light of a recent report from the Associated Press (click here for one condensed summary) about high levels of pharmaceuticals in the municipal water supply, one pharma pundit (who has a blog on our site) recast the infamous quote. A large part of the problem stems from consumers, who dump expired pills or medications down the drain. However, what about industry's role? Drug companies are meeting EPA standards, but EPA standards haven't yet taken into account the impact of this unforeseen waste stream. The analytical science required and the cost of toxicological tests make it highly unlikely that there will be any regulations set any time soon. APIs play some role in the problem. One pharma professional recalls his years at a generic drug manufacturer, where all the process water was recycled and used to irrigate the grounds (although nobody would eat any of the lush fruit growing there). Last summer, studies of water discharge of pharmaceuticals in India offered some insights. API manufacturing expert Girish Malhotra has some views of his own on this subject. The key, he says, is intelligent process design and adoption of Quality by Design. Girish writes extensively about QbD on his blog. Below, an excerpt from reporting as it appeared in Chemical Week. Researchers at Gothenburg University (Gothenburg, Sweden), led by Joakim Larsson, have identified pharmaceuticals, some at levels unprecedented anywhere in the world, in wastewater discharged from pharmaceutical manufacturing plants near Hyderabad, India. The findings were published July 6 online by the Journal of Hazardous Materials. The researchers’ findings are based on an analysis of effluent from a wastewater treatment plant operated by Patancheru Enviro Tech (Patancheru, India), which serves manufacturing plants owned by about 90 drug manufacturers including Dr Reddy’s (Hyderabad), Nicholas Piramal (Mumbai), and Mylan Laboratories (Canonsburg, PA) at Patancheru, near Hyderabad. The treatment plant receives 1,500 cu meters/day of wastewater and discharges effluent into the Nakkavagu river, a tributary of the Manjira river, from which the city of Hyderabad sources its drinking water The researchers identified 59 pharma products in the effluent, of which 21 were present at concentrations above 1 micro-gram (µg)/liter and 11 were found at concentrations above 100 µg/liter. "To the best of our knowledge the concentrations of these 11 drugs were all above the previous highest values reported in any effluent," the researchers say. Several broad-spectrum antibiotics were discovered within the effluent, raising concerns about resistance development among local people. The antibiotic ciprofloxacin was the most abundant drug in the effluent and was present at a concentration of 31,000 µg/liter. The concentration corresponds to a discharge of about 45 kg of active pharma ingredient (API) during a 24 hour-period—equivalent to the average amount of ciprofloxacin consumed in Sweden, which has a population of nine million, over a five-day period. Several companies in the Hyderabad area produce ciprofloxacin, the researchers say. The total volume of the 11 most abundant active substances released into the effluent over a 24-hour period would cost more than €100,000 ($136,000), even if generic brands were selected, if they were purchased as final products in a Swedish pharmacy, the study says. Larsson stands by the study’s findings and says that "the production cost for the active ingredients would only constitute a very small fraction of the price of the final products." The financial cost of the waste to the manufacturers is about 100th of the price of the final product, an unnamed pharma manufacturing expert says. It had been widely accepted, prior to Larsson’s study, that the main route for human pharmaceuticals entering the environment was via domestic wastewater treatment plants. "Arguments have been raised that highly controlled production processes, as well as the great value of the drugs, would ensure that only minor amounts of active substances would escape," the researchers say. "To our best knowledge there is no publicly available peer-reviewed information available that can confirm or reject this claim." The study raises questions about the effluent streams of pharmaceutical manufacturers in other parts of the world, Larsson tells CW. The study’s results demand an increased focus on the potential release of APIs from production facilities in other regions, he adds. Other experts agree, including an unnamed former pharma plant inspector at the U.S. EPA, whom—like Greenpeace—suggests that the pollution in Petancheru is the result of inadequate capacity of the waste treatment plant. Additionally, inefficient production processes mean that high levels of waste are coming out of plants producing APIs in the West, as well as India, he says. "It’s inefficient as hell, but as consumers we’re prepared to pay a high price for the medicines," the former EPA inspector says Later, Girish commented to the magazine, API concentrations at high levels have a toxicological influence on the environment and should be controlled. However, he says that there appear to be few if any collective ecotoxicological standards for many chemicals. Malhotra suggests that industry must establish individual and respective safe toxic levels of various organics and control them to below defined levels in water bodies and soil around production plants. Malhotra says there are two ways to bring the toxicity of disease-curing chemicals below toxic levels: By improving pharmaceutical processing and manufacturing technologies, and reducing organic levels in effluent waste. We will be covering this issue in our next issue of Pharmaceutical Manufacturing, along with a look at what pharma is doing to "walk the talk" about sustainable development.