The Man at Work Collection--Studies in Sustainability
Installment Eleven: “Sustainability in the Pharmaceutical Industry”
By Deborah L Jackman, PhD, PE, LEED AP™
by Vida Gabor, oil on panel
The use of herbs and other animal and plant extracts to treat disease is as old as human civilization. The Bible states,
“And on the banks, on both sides of the river, there will grow all kinds of trees for food…. Their fruit will be for food, and their leaves for healing.” (Ezekiel 47:12, ESV)
Yet, prior to the middle of the 19th Century, medicines were largely formulated and dispensed locally by traditional herbalists, shamans, chemists, and physicians, using naturally derived (i.e. non-synthetic) ingredients. The pharmaceutical manufacturing industry as we now know it, where drugs are chemically synthesized and manufactured in bulk at a centralized location and then dispensed through local pharmacies, began in the late 1800s, as an off shoot of the nascent synthetic chemical industry that began in Europe (especially in Germany). Today’s retail pharmacies do little of their own drug formulation, acting instead as a point of distribution of drugs which are centrally manufactured by pharmaceutical companies. The subject painting, The Apothecary, represents the transitional period, spanning a period of roughly the middle 19th through the middle 20th century, during which druggists (i.e. apothecaries), who were trained in chemistry and basic pharmacology, sold both pre-manufactured drugs and “patent” medicines, but also formulated drugs in-house to sell to local clientele. The assortment of chemicals, weigh scales, flasks, and other chemical paraphernalia displayed in the painting are evidence of the technical skills of the resident apothecary in formulating drugs for his customers. In addition to providing medicines to his customers, this apothecary likely knew his customers on a first name basis and could offer them moral support and a sympathetic ear. Today’s “Big Pharma” can offer us none of the human touch and compassion that the apothecary could offer, yet as a tradeoff, we can be assured of the efficacy and safety of the medicines we consume. For every traditional potion and drug formulation that healed our ancestors, there were many based on faulty science and superstition which poisoned or even killed. Arguably, we are in a much better place, in the early 21st century, in terms of having access to effective and life-saving drugs than at any time in human history. Yet, as with most technological advancements, there are also downsides. In addition to the loss of the “personal touch” that the apothecary could offer, Big Pharma has also introduced negative environmental impacts.
The significance of the negative environmental impacts for which the pharmaceutical industry is responsible is magnified by the sheer size of the industry. In 2012, nearly ten percent of all money spent on healthcare in the United States was spent on prescription drugs. Out of the $2.8 trillion dollars spent on healthcare overall, $263.3 billion dollars were used to purchase prescription drugs.  The pharmaceutical industry is big business, and like most big businesses, it has a huge environmental footprint. However, unlike many other industries, it has been relatively slow in recognizing and addressing its negative environmental impacts. The reasons for this tardiness are complex--the conservative nature of the healthcare community overall; large profit margins that until recently were largely unquestioned and which led to a degree complacency within the industry; and little public recognition of environmental threats unique to pharma--among others. In marketing products that have such a direct impact on human health, pharmaceutical manufacturers have been understandably cautious in changing manufacturing operations or processes that could in some way negatively impact product quality. This means that some of the techniques (for improving operational energy efficiency and minimizing pollution through the substitution of less toxic raw materials) that have become commonplace in the broader chemical industry, have been slow to arrive within Big Pharma. Historically high profit margins and little government scrutiny of drug costs meant that many energy conservation strategies that both reduce manufacturing costs and reduce the operational carbon footprint, and which have been broadly employed within the larger manufacturing sector, are only now being adopted by the pharmaceutical industry. And, until recently, the general public has been largely unaware of the dangers related to drugs entering surface waters through sewage treatment systems and persisting in the environment. However, the landscape is now changing and the pharmaceutical industry is being forced to more carefully consider its environmental impacts. It is slowly and cautiously undertaking a “greening” of its operations. This article will explore the negative environment impacts of the pharmaceutical industry and will look at recent initiatives intended to reduce these negative impacts.
Environmental Impacts of the Pharmaceutical Industry:
As noted earlier, the modern pharmaceutical industry is an off shoot of the synthetic organic chemical industry. Many of the same chemical techniques used to manufacture industrial solvents, coatings, paints, and plastics are used by the pharmaceutical industry to manufacture drugs. Thus, it is not surprising that many of the same environmental issues that occur in chemical manufacturing affect the pharmaceutical industry: high energy costs and a large carbon footprint, the treatment and disposal costs associated with contaminated waste water streams, the safe handling and disposal of toxic solvents, air emissions, etc. Solutions to these environmental challenges were originally pioneered by the broader chemical manufacturing industry and are well documented. They can be translated relatively easily into solutions applicable to pharmaceutical plants. For a sampling of the ways in which the pharmaceutical industry has adapted environmental controls and waste minimization strategies borrowed from the broader chemical manufacturing industry, the reader is encouraged to review references  through . References  and  focus on reducing energy consumption as a means of reducing the carbon footprint of a pharmaceutical plant through HVAC system improvements and process energy recovery strategies, respectively. Reference  discusses the use of a life-cycle assessment tool, the Fast Life-cycle Assessment of Synthetic Chemistry (FLASCTM ) to quantify the broader environmental impacts of a pharmaceutical manufacturing operation. FLASC allows not just the impact of energy use to be evaluated, but also the impact of toxic materials used during the manufacturing process. Finally, reference  builds the all-important business case that employing “green” manufacturing strategies isn’t just good for the environment, but also leads to lower production costs and can increase profitability.
In addition to dealing with impacts similar to those encountered by chemical manufacturers, the pharmaceutical industry must deal with the unique environmental impacts resulting from the pharmacologically active nature of their products. It is this second category of environmental impacts that are perhaps the greatest environmental challenge faced by pharmaceutical manufacturers today. The health dangers associated with the unintended release of pharmacologically active substances into the environment have only recently become widely recognized and discussed. Solutions are yet to be fully defined or implemented. Therefore, it is this second category of environmental impacts that will be the major focus of the remainder of this essay.
Provisions of the Clean Water Act (CWA) mandate that industries pretreat any waste water generated by their facilities before discharging it to publically-owned treatment works (POTWs) in order to remove hazardous substances that cannot be removed or neutralized during conventional sewage treatment processes used in the POTW. This has been the law of the land (in the United States) since the CWA was enacted by Congress in 1976. The pharmaceutical industry is no exception. It must pretreat its waste water to remove excessive solids, adjust water pH to relatively neutral levels, and to remove a predefined list of toxic organic chemicals and solvents, used during manufacturing processes. The list of substances that must be treated and the levels to which they must be removed are defined in the Code of Federal Regulations (CFR), Chapter 40, Part 439. What is fascinating to note, however, is that there is no requirement within the CFR that any residue of the actual drugs produced be removed from waste water prior to discharge to the POTW. What this means is that various drugs could be present in waste waters discharged from pharmaceutical manufacturers. There is no guarantee that such drugs would subsequently be destroyed by the POTW prior to discharge to surface waters because conventional sewage treatment processes are not designed to break down specific drugs. Many drugs are comprised of chemicals that are by design very stable, in order to ensure long shelf lives. Thus, up until recently, the possibility of trace levels of drugs entering our drinking water and inadvertently being ingested by humans and animals, has not been considered by regulators or addressed in a systematic manner.
Some pharmaceutical industry apologists have scoffed at the idea that there is any validity to the concern that so-called active pharmaceutical ingredients (APIs) exist at any significant levels in pharmaceutical manufacturing waste waters discharged to local POTWs in the United States. These industry spokespersons argue that the monetary value of finished pharmaceutical products is so great, and the efficiency of drug manufacturing processes is so high, that APIs are essentially completely recovered from process streams before any waste water stream is discharged. Kessler  debunks this claim. She cites and summarizes a study conducted by the United States Geological Survey (USGS) between 2004 and 2009. In this study, researchers collected water samples from the receiving stream and effluent of three POTWs located in the state of New York. Two of the three POTWs received at least 20% of their receiving waters from large pharmaceutical manufacturers. Median levels of several APIs, including oxycodone, methadone, diazepam (Valium), and four other lesser known barbiturates and amphetamine compounds, of between 2 and 400 parts per million were present in the discharges from the two POTWs that received significant influent from the manufacturing plants. In contrast, levels of these same APIs in the discharge from the POTW that did not process effluent from pharmaceutical plants never exceeded 1 part per million and were typically considerably lower. Furthermore, very high maximum concentrations of 1,700 parts per million of oxycodone and 3,800 parts per million of metaxalone were found in the effluent associated with the two POTWs that served the pharmaceutical manufacturing plants. According to Kessler, at 1,700 parts per million, a person would only need to drink 1.4 liters of this effluent to receive dosages of oxycodone that would roughly equal those received when the drug is consumed as prescribed by a physician. Some researchers have subsequently noted that it would be unlikely that a person would drink effluent directly from a POTW, and that such waters are subsequently diluted, filtered, and disinfected by municipal drinking water plants before humans consume them, thereby further diluting the impacts of these APIs on human health. However, the effects on human health of many drugs at very low levels on a long term basis are not well understood. So the study results reported by Kessler should still be of concern. Furthermore, fish that live in and wildlife that drink from surface waters that are near the POTW discharges would receive much higher dosages of these APIs, which could negatively impact wildlife ecology. Many human drugs, including hormones (such as those found in birth control pills) and steroids have been shown to produce endocrine disruption in many species of wildlife. The most significant aspect of the USGS study is that it was the first study that proved that elevated API levels in surface waters can be attributed directly to pharmaceutical plant discharges. It has spurred additional research, which is ongoing.
Another pathway by which APIs enter our surface and drinking waters is via consumers. When a person is prescribed a drug, some of that drug is metabolized and some is excreted in sweat, urine, or feces. Excreted drugs eventually all end up in the sewage treatment system via waste water from toilets and bathing. A second route by which consumers allow drugs to enter the environment is when they dispose of drugs. When a consumer disposes of expired or unused drugs by flushing them down the toilet or washing them down the sink drain, such drugs also enter the sewage treatment system. And like the case of APIs entering POTWs directly from pharmaceutical plant discharges, the receiving POTW cannot fully treat or remove them. Solving this problem is far more difficult than solving the problem caused by direct pharmaceutical plant discharges because it involves treating thousands of different chemical compounds originating from millions of different sources. It would be relatively easy from a purely technical standpoint for pharmaceutical manufacturers to develop additional treatment processes to ensure removal of APIs from their effluent. Granted, such manufacturers would likely balk at the added cost and would heavily lobby the government to not enact the required legislation. But, assuming these political barriers could be overcome, it is an easy technical problem to solve, largely because it involves treating well-defined point sources. In the case of APIs introduced by consumers, both the large array of possible drug types and the need to alter human behavior present immense challenges.
Since the completion of the ground-breaking USGS study cited by Kessler , there has been an explosion of research on the subject of APIs in the environment—both those originating directly from pharmaceutical plant discharges and those caused by improper disposal of drugs by consumers. An excellent source that summarizes much of this on-going research is found at the USGS webpage dealing with the subject of emerging contaminants in the environment .
Addressing APIs in the Environment:
As noted earlier, APIs enter the environment both as point source discharges from pharmaceutical plants and by the actions of consumers who excrete drugs or who dispose of unwanted drugs inappropriately.
Addressing point source discharges by pharmaceutical manufacturers is not a technical problem (because needed treatment technologies are well-understood), but it poses a formidable political challenge. Revisions to 40 CFR Part 439, the government regulations governing waste water discharges from pharmaceutical plants, would be required in order to mandate pretreatment of APIs. Our current political climate features a dysfunctional Congress coupled with a pharmaceutical industry that heavily lobbies the government for favorable legislation. Between 1998 and 2012, the pharmaceutical industry spent a whopping $2.6 billion dollars  on lobbying activities. Given these conditions, the likelihood of any immediate regulatory change is low. Ironically, hope for changes in how pharmaceutical companies operate with regard to APIs in the environment may rest with the industry itself. Various industry publications have begun to feature articles about this problem and some discussions have begun about the costs associated with allowing APIs to enter the environment via waste water discharges. Costs include both lost revenues by allowing drugs to be discharged (as opposed to being recovered and sold) and potential liability costs associated with adverse health events being causally linked to APIs. If there is one thing that Big Pharma is responsive to it is profit, so perhaps tying self-regulation to profitability will ultimately result in voluntary reductions of API discharges.
How to address APIs that enter the environment by way of inappropriate disposal by consumers or due to excreted drugs is challenging from both a technical and behavioral perspective. Technical complexity is the result of trying to quantify the impacts of literally thousands of different types of drugs—each with its own potential side effects and each requiring different types of disposal and destruction strategies. Some progress is being made on the local and state government levels to create drug “take back” programs, loosely modeled on various “clean sweep” programs that many municipalities instituted in the 1970s and 1980s to keep consumers from dumping harmful substances like pesticides and waste oil down the drain. Drug take back programs attempt to incentivize consumers to dispose of drugs appropriately by providing convenient means to drop off unused or expired drugs rather than to dump them down the drain. As with any strategy that requires people to modify their behavior, the keys to success are sustained public education as to the dangers of improper drug disposal and patience, since such behavioral modifications require time to become established. Addressing APIs that enter the environment through excretion of drugs is perhaps the most difficult issue of all because people can’t prevent drug excretions by behavioral modification short of not taking needed drugs. As environmental research into the impacts of APIs continues, it is likely that certain drugs will be identified as more problematic than others (e.g. hormones and other endocrine disrupters). It may then be possible to require upgrades to unit treatment processes at POTWs to incorporate treatment technologies that target especially problematic classes of drugs. Flyborg, et.al.  piloted changes to a POTW in Sweden that involved adding nanofiltration and ozonation to existing treatment processes in order to remove 95 different drugs. All but three were successfully removed down to desired levels. The authors indicated that the remaining three drugs could have been removed were the POTW to use a tighter nanofilter. However, using a tighter nanofilter was not determined to be cost effective. This study illustrates the trade-offs we must make between removing unwanted contaminants and keeping POTW operations cost effective. Such tradeoffs must occur in the context of a larger societal conversation.
Daughton and Ruhoy  provided what is probably the most far-reaching discussion of how to deal with APIs that enter the environment through excretion and improper disposal by consumers. Their focus is on ways that the healthcare system can address the problem by preventing inappropriate prescribing. They coin the phrase “PharmEcovigilance”, which is an extension of the well-understood (within the pharmaceutical and healthcare industries) practice of pharmacovigilance. Pharmacovigilance involves the collection, detection, assessment, monitoring, and prevention of adverse drug reactions through a system of patient and physician reporting and ongoing medical research on appropriate uses and dosages of drugs. Daughton and Ruhoy propose to extend this to drugs that enter the environment post-consumer. Their proposed system of PharmEcovigilance would include a number of far-reaching and controversial strategies including:
- Physicians should encourage patients to take all drugs prescribed so as to reduce the need to dispose of unwanted drugs
- Physicians must practice so-called “rational” prescribing, in which they limit prescribing drugs for off-label uses without good reason and limit the prescription of antibiotics (which when they enter the environment promote antibiotic resistant strains of “superbugs”) except for confirmed cases of bacterial infections (since antibiotics are ineffective against viruses.)
- Physicians should prescribe trial prescriptions in cases where a patient has not received a particular medication before. This would reduce instances of the patient disposing of a full prescription of a drug that turned out to be ineffective in treating that patient.
- Physicians should consider prescribing placebos to some patients whose conditions might resolve on their own, but who demand that the physician prescribe them a medication.
- The healthcare system should increase its vigilance of patients who might engage in “doctor shopping” as a means to get unneeded prescriptions of drugs.
- Physicians must ensure that patients understand the hidden dangers of over-consuming drugs and should work with patients to reduce the numbers of different medications that patients are prescribed unless there is a clearly demonstrated medical benefit for multiple drugs.
- Educate consumers about the appropriate means of disposing of unused or unwanted drugs.
- And, perhaps, most radical of all, in light of Western medicine’s reliance on drugs—prescribe exercise, good nutrition, and sufficient rest instead of drugs, whenever possible.
It seems appropriate to end this essay with the PharmEcovigilance proposals of Daughton and Ruhoy foremost in mind because they represent the coming full-circle of attitudes in the pharmaceutical and healthcare industries. In the days when the Apothecary practiced his profession, effective listening and communications with patients in order to customize their treatment was deemed as important as the drug that was ultimately prescribed. Such a personalized approach should be returned to today, not only to help prevent the negative environmental impacts of APIs, but to reduce overall healthcare costs, and to better serve patients.
References and Further Reading:
- “National Health Expenditures, 1960 through 2012”, the United States Center for Medicare and Medicaid Statistics, Retrieved on December 10, 2014, from http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/tables.pdf
- Goldschmidt, N., “First Steps for Sustainable Bio/Pharma HVAC”, Engineered Systems, August, 2009, p. 26-34.
- Nikolova, D., Ivanov, B., and Dobrudzhaliev, D. “Energy Integration in Antibiotic Production using Heat Storage Tanks”, Trakia Journal of Sciences, Vol. 9, No 4, 2011, pp 30-38.
- “Filling Gaps during Carbon Footprint Studies to Design Green Pharmaceuticals”, conference presentation sponsored by Glaxo Smith-Kline, Inc., at the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable, November, 2013.
- Ramesh, D., “Cost Cutting Becomes the Pharma Industry’s Mantra: Green Technology Gains Importance,” Chemical Week, September 28/October 5, 2009, p. 24-28.
- Kessler, R., “Pharmaceutical Factories as a Source of Drugs in Water,” Environmental Health Perspectives ,Vol.118, No. 9, September, 2010, p. A383.
- “Emerging Contaminants in the Environment”, United States Geological Survey webpage, retrieved on December 17, 2014, from http://toxics.usgs.gov/regional/emc/
- Potter, W., “Big Pharma's Stranglehold on Washington,” The Center for Public Integrity, February 11, 2013, retrieved on December 16, 2014, from http://www.publicintegrity.org/2013/02/11/12175/opinion-big-pharmas-stranglehold-washington
- Flyborg, L., Björlenius, B., and Persson, K.M. “Can Treated Municipal Wastewater be Reused after Ozonation and Nanofiltration? Results from a Pilot Study of Pharmaceutical Removal in Henriksdal WWTP Sweden”, Water Science and Technology, 61.5, 2010, p.1113-1120.
- Daughton, C.G., and Ruhoy, I.S., “The Afterlife of Drugs and the Role of PharmEcovigilance”, Drug Safety, Vol. 31(12), 2008, p. 1069-1082.
In Spring 2015, look for the twelfth and final installment of this essay series. In “Its Just Good Business,” we will explore the ultimate driver for successfully addressing the environmental concerns discussed throughout the series—the economics of sustainability. We will look at innovative economic models that can be used to help justify sustainable practices. The painting which will inspire this discussion is The Money Lenders, by Dutch painter Quinten Massys (1465/66-1530)