Medicininių atliekų ES reglamentavimas

Chapter 31
Pharmaceutical Waste
S. Castensson
31.1 Introduction
Pharmaceuticals form a group of substances that are of considerable importance for society as healthcare tools. A variety of pharmaceuticals can now be detected in surface, ground, and drinking waters (Kümmerer 2004, 2008). This raises concerns about the potentially adverse environmental consequences of this contamination. The risk is directly proportional to the active concentration of the chemical substances in various environmental compartments, and pharmaceutical waste adds to that risk if it is not managed properly.

Pharmaceuticals are widely distributed, and there is a consistent global increase in the use of potent pharmaceuticals driven by drug development, an aging population in Western countries and the efforts to improve health in developing countries. Following this use is a corresponding increase in the generation of pharmaceutical waste. The reduction of waste generation and risk of any leakage of toxic drug substances into the environment from waste is an important task. The waste and disposal problem starts with the production of the active pharmaceutical ingredient (API) and finishes with the final disposal of a pharmaceutical product. During the manufacture and use of pharmaceuticals, lots of materials become contaminated with an API increasing the waste volume. Pharmaceutical waste is not only an environmental issue. Like other waste management, it is part of many peoples’ working conditions in respect to how it is handled, contained and disposed of. When the material entails a serious hazard, it requires special handling to ensure safety. Where there are issues with higher risk products, e.g., controlled drugs, increased security in handling pharmaceutical waste is also required. Proper pharmaceutical waste management is a new and highly complex frontier in environmental management. Occupational health and safety is a highly integrated issue in the management of certain pharmaceuticals like chemotherapeutics, and the waste generated from these involve a significant hazard. This chapter focuses on the handling and disposal problems of finished pharmaceutical products in the EU and USA, irrespective of being used or unused, and some related contamination problems.
31.2 Planning Waste Management
Pharmaceutical waste may be present in any of the common physical forms like solids, liquids and gases. The waste can be categorized in several ways, e.g., depending on source, physical state, hazard, security, handling and disposal.
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31.2.1 Legislation
Management of pharmaceutical waste is especially challenging given the complexity of the governing regulations.
European Union
In the European Union (EU), a legislative framework (outlined in Fig. 31.1) forms the base for practice. Waste management planning is based on three directives that describe the obligations: the Directive on Waste (75/442/EEC), the Directive on Hazardous Waste (91/689/EEC) and the Directive on Packaging and Packaging Waste (94/62/EC). The Directive on Waste (75/442/EEC) lays down requirements for all types of waste, unless they are specifically regulated by other directives. Pursuant to the two first directives mentioned, a list of wastes is included in a Commission Decision (2000/532/EC). Pharmaceutical waste categories are coded and fully defined by six-digit codes in the list of wastes in Chapter 18 (Wastes from human or animal health care and/or related research, except kitchen and restaurant wastes not arising from immediate health care) and in Chapter 20 (Municipal wastes; household waste and similar commercial, industrial and institutional wastes, including separately collected fractions). Cytotoxic and cytostatic medicines are considered hazardous waste and consequently subject to special provisions. Cytotoxicity means that the drug will harm or kill cells, and cytostatics are drugs used to block the growth of cancer cells. Cytotoxic drugs do not
Fig. 31.1. Overview of EU directives on waste (European Topic Centre on Waste and Materials Flows 2003). Regulations pertinent to pharmaceutical waste are shown in bold
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specifically affect cancer cells, but all dividing cells. This makes cytotoxic drugs extremely hazardous to living organisms. The EU strategy for waste management includes the prevention and precautionary principle to secure a reduction in the impacts of waste on human health and the environment and especially to reduce the hazardous substances in waste. Dir. 2004/27/EC amending Dir. 2001/83/EC on the Community code relating to medicinal products for human use and Dir. 2004/28/EC amending Dir. 2001/82/EC on the Community code relating to veterinary medicinal products both consider the precautionary and safety measures to be taken for the disposal of waste products, together with an indication of potential risks presented by the product to the environment. Member States are obliged to ensure that appropriate collection systems are in place for medicinal products that are unused or have expired.
United States of America
Laws governing pharmaceutical waste have existed for many years, and the goal of the regulations is to prevent harm to human health and environment. The following framework can be identified:
 The Resource Conservation and Recovery Act (RCRA) of 1976;  Clean Water Act;  Clean Air Act;  Environmental Protection Agency’s Audit Policy of 12/1995; updated 4/2000;  Community Right to Know Act;  Hospital/Medical/Infectious Waste Incineration Rule;  Land Disposal Restrictions Regulations.
Federal RCRA regulations apply to hazardous pharmaceutical waste. Hazardous wastes are divided into two categories: (1) listed wastes that appear on one of four lists of hazardous waste (F, K, P, and U), and (2) characteristic wastes exhibiting certain hazardous properties – ignitability, corrosiveness, reactivity, and toxicity. Pharmaceuticals are found on the P and U lists. Because of toxicity, some chemicals and heavy metals used in drug formulations appear on the D-list. Drug formulations containing these chemicals and heavy metals are of concern in solid waste landfill environment above certain concentrations. For non-regulated hazardous pharmaceutical waste, the best management practice is applicable. This practice encourages avoiding the drain disposal of any waste pharmaceuticals, with emphasis on those that are hazardous. It is always appropriate to manage drug waste at a higher level of care than required by regulation. When it comes to the proper disposal of prescription drugs at home the present federal guideline recommends unused, unneeded, or expired drugs are to be taken out of their original containers and thrown in the refuse. Where pharmaceutical return programs or community solid-waste programs exist, which allow the public to bring unused drugs to a central location, these are advocated as a proper disposal. A few medicines, mainly controlled drugs, are recommended to be flushed down the toilet for security reasons (Office of National Drug Control Policy 2007).
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31.2.2 Waste Sources
Spills/breakage, partially used vials and bottles, discontinued and unused preparations, and outdated pharmaceuticals are all scenarios where pharmaceutical waste is generated. In addition, the devices used to administer drugs and general compounding in hospitals and pharmacies add to the waste volume. A significant waste source is pharmaceutical dosage forms that contain large residues of API after normal use (see below). A transdermal patch is a dosage form designed to maintain a consistent release rate during the time of application to the skin. An excess of twenty times the amount of drug that will be absorbed is commonly loaded into the product. The surplus is needed to achieve the stable concentration gradient to provide a consistent drug release. When the API is an estrogen, the environmental concern of proper disposal of used transdermal patches is imperative as minute concentrations of endocrine disruptors are known to have detrimental effects on aquatic species and possibly on human health and development (Sumpter et al. 2005). Table 31.1 reviews transdermal patches marketed in Sweden 2007 that contain estrogens and the residual amounts after use.
31.2.3 Waste Streams
Pharmaceutical waste is not one, but many distinct waste streams that reflect the handling and usage of pharmaceutical products. Two main streams can be identified. The first is connected to the use of pharmaceuticals by people in primary care either for themselves or for their pets. This stream may also include the use of drugs in livestock farming. The second main stream is generated by hospital care and other care institutions and also establishments in which research activities may be included. Healthcare establishments for humans or animals produce a range of various wastes, which according to regulation belongs to five basic groups: municipal, medical, infectious medical, hazardous, and low level radioactive waste.
Unused Medicine
When a patient has finished a drug treatment, there may be some unused drug left. The unwanted or leftover drug can be disposed of by the patient at a pharmacy, another designated place, or it is disposed of in some other way. Drugs returned to pharmacies have been studied in Sweden since the 1970s in order to understand what drugs are returned and how much is left in the packs in relation to age and sex of the patients. A few studies have been published from other countries (Socialstyrelsen 2004). A comprehensive study in Sweden by Ekedahl et al. (2003) showed a return to pharmacies of 4.6% of the total sale in Defined Daily Doses (DDD) and 3.8% of totally sold packs. 51% of the packs had expired and 65% had more than two thirds left (38% were unopened). Data published from other countries generally report lower proportion of unopened packs; Great Britain 20% (Hawksworth et al. 1996), Germany 24% (Bronder and Klimpel 2001). Several international studies report that a larger proportion of unused medicines are returned by the elderly (Braybrook et al. 1999, Hawksworth et al. 1996). A
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similar skew is described by Ekedahl (2003) reporting 60% of the patients are ≥65 years old and return 64% of all packs. Figure 31.2 is adapted from the same study and shows how few patients return the majority of unused prescription drugs to pharmacies.
Used Medicine with Residue
All used packs will contain some pharmaceutical substance residues. Packs with visible residues should be classified as pharmaceutical waste, demanding handling and
Table 31.1. Transdermal patches containing estrogens authorized on the Swedish market 2007
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disposal procedures that give proper protection to people and the environment. An empty pack that has not contained hazardous API can be discarded as municipal waste if truly empty. However, a lot of pharmaceutical products are designed with a packaging that is not transparent. Here visual inspection is impossible and some of these, like tubes and aerosol cans, may contain substantial residues when used. It can be seen in Table 31.2 that several pharmaceutical dosage forms contain a significant residual amount even when used correctly. The controlled collection and disposal of these products after use will lessen the environmental risks.
Packaging materials and administration accessories consume a small, though significant proportion of natural resources. They can impact the environment through pollution caused by incineration and landfills. No pharmaceutical packaging is reused, but the outer packaging of pharmaceuticals is usually a non-contaminated material that can undergo recovery or recycling together with empty non-hazardous pharmaceutical packs by segregation as cardboard, paper, plastic, glass, and metals. Plastic is the most common packaging material, followed by cardboard and paper. The plastic material is dominated by polyethylene and polypropylene without notable environmental pollution problems. Other environmentally accepted plastic materials are acetal plastic, ethyl-vinyl-acetal plastic, polyamides, polyesters, polycarbonates, polyurethanes, and styrene plastics. Polyvinyl chloride (PVC) is questioned environmentally because of potential pollution of the environment during manufacturing and disposal. PVC is the dominant plastic in blisters.
Contaminated Material
Products such as personal protective equipment, materials used to perform routine cleaning and decontamination as well as spill clean up materials may become contaminated. When contamination with a hazardous material is suspected or known, the resulting waste will normally receive the same regulatory status as the original classified API component.
Fig. 31.2. Number of returned packs of prescribed drugs and number of patients returning divided on number of packs per patient. 5% of the patients are returning 36% (≥24 packs/patient); 10% are returning 50% (15–101 packs/patient); 69% are returning 22% (1–4 packs/patient)
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Sharps, needles and syringes with needles can be collected in containers made of hard plastic. There are also several devices available for cutting and collecting the needle, making it possible to segregate the syringe and the needle for separate disposal.
31.2.4 Collection and Segregation
Hospitals and Care Centers
In order for waste not to pose a threat to human health and the environment, they have to be properly identified, segregated and disposed of. Unfortunately, due to imperfect procedures, the waste from different groups becomes mixed together. As a result, the waste has to be managed at a higher standard according to regulation and thus requires costly methods of treatment. In reality, most waste produced by the healthcare sector is simply non-hazardous municipal waste that can be recovered and recycled. While the first priority has to be identifying, segregating and properly managing hazardous pharmaceutical waste, all other pharmaceutical waste should be collected and segregated in a systematic way for correct disposal. With proper segregation in place, the amount of infectious medical waste, hazardous waste and radioactive waste can be reduced to 2–25%, depending on the type of
Table 31.2. Pharmaceutical dosage forms with significant residues after normal use (adapted from Castensson and Riemsdijk, to be published)
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establishment and the scope of services it provides. The hazardous waste segregation system must be adapted to the waste treatment technology applied (Health Care Without Harm Europe 2005).
Non-Institutional Care
The results from a questionnaire sent to the associations for pharmacies in Europe in 2003 are presented in Fig. 31.3. In the Netherlands, Spain and Sweden, all pharmacies were active in the collection of leftover medicine. In nine countries, all pharmacies accepted taking back leftover drugs from the public, in five others some pharmacies would do this, and in one country no leftover drugs were accepted. In Belgium and France, some pharmaceuticals were segregated for recycling as donations, which is disparate to WHO Guidelines for drug donations from 1999 (Socialstyrelsen 2004). A European survey of twenty-eight countries performed by the European Federation of Pharmaceutical Industries and Associations (2007) indicated a formal product return scheme of leftover drugs in twenty countries. In Sweden (population 9 million) approximately five per cent of the drugs counted as DDDs collected from pharmacies will never get used. About seventy-five per cent of the leftover drugs are returned to pharmacies by the public for controlled incineration, which amounts to more than 900 tons yearly including packaging.
Fig. 31.3. Results of a European survey 2003 on the collection of unwanted medicine at pharmacies from the public. Shaded boxes confirm the questions presented in the questionnaire (adapted to Socialstyrelsen 2004); a: most on request, b: one chain active, c: unopened, essential and listed drugs with remaining shelf-life, d: narcotics, e: “normal” pharmaceutical waste is disposed of with other waste for incineration, f: no references
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In the USA, there is no national program or regulation for the collection of unused and expired drugs, but local programs are encouraging people to dispose of them at designated drop sites.
31.2.5 Treatment and Disposal
According to the European Waste Catalogue, pharmaceutical waste is classified by six-digit codes:
 18 01 01 (18 02 01) Sharps (non-infectious);  18 01 03* (18 02 02*) Special requirements in order to prevent infection;  18 01 08* (18 02 07*) Cytotoxic and cytostatic medicines;  18 01 09 (18 02 08) All other medicines;  20 01 31* Cytotoxic and cytostatic medicines;  20 01 32 All other medicines.
The codes within brackets represent waste involving animals, and the codes marked with an asterisk are considered hazardous waste. The use of incineration as a disposal method is regulated in the EU by the directive Incineration of waste (2000/76/EC). The method has the drawback that it may cause pollutants. This is handled by regulations stipulating limit values on the emission to the atmosphere. Also, the temperature of the gases in the process should be at stipulated values depending on the waste content. In the EU, the incineration technology is widespread for disposal of the solid waste (see Fig. 31.3). However, liquid waste may be disposed of down the drain, as environmentally adapted procedures just recently have come into focus. In the USA, hospital pharmaceutical waste is generally discarded down the drain or in landfill sites, except chemotherapy agents, which are often sent to a regulated medical waste incinerator. The statutory definition of hazardous waste provides sound reasoning for broadening the range of chemotherapeutic drugs that should be managed as hazardous waste. The statute defines the term “hazardous waste” to mean a solid waste or combination of solid wastes that because of its quantity, concentration, physical, chemical, or infectious characteristics may (1) cause, or significantly contribute to an increase in mortality or an increase in serious irreversible, or incapacitating reversible, illness; or (2) pose a substantial present or potential hazard to human health or the environment when improperly treated, stored, transported, or disposed of, or otherwise managed (Hospitals for a Healthy Environment 2006). Pharmaceuticals are designed to be resistant to biological degradation. Wastewater treatment plants are designed to remove conventional pollutants such as suspended solids and biodegradable organic material, but they are not designed to remove low concentrations of synthetic pollutants such as pharmaceuticals. The removal efficiency of various wastewater treatment technologies appear to be chemical-specific. Land filling pharmaceutical waste should be avoided, both for environmental and security reasons. Drugs added to a landfill will eventually leach into groundwater or be deliberately pumped out from its leaching beds.
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Thermal destruction of discarded drugs provides the closest match to best management practice at this time. Non-incineration medical waste treatment technologies may sometimes be an alternative for pharmaceutical waste (Health Care Without Harm Europe 2004).
31.3 Minimizing Pharmaceutical Waste
There are inherent limitations in the practice of substituting a hazardous drug since this hazardous nature of the API often provides the therapeutic effect. However, an environmentally preferable product choice can sometimes be made. This concerns firstly those products that may contain heavy metals or persistent, bioaccumulating and highly toxic ingredients or very persistent and very bioaccumulating chemicals. Source reduction is an important key to reducing the amount and toxicity of waste. One way to decrease the volume of unused medicines is to have a greater choice of packaging sizes. Smaller packs, especially when initiating a new longer treatment and individualized dispensing have great potential to decrease the amount of leftover drugs. Working groups in medical establishments monitoring and enhancing a waste reduction program will greatly influence the amount of waste that is destined for ultimate disposal. Detailed procedures in performing a program can be found in Hospitals for a Healthy Environment (2006) and Health Care Without Harm (2005). The potential benefits of waste minimization for society are environmental risk reduction and cost reductions. Healthcare establishments win better compliance with regulatory standards, enhanced occupational health and safety and improved community relations.
31.4 Conclusion
Pharmaceutical waste management is especially challenging, given the complexity of the problem. Proper management of hazardous pharmaceutical waste is first priority, but careful consideration should be given to manage all pharmaceutical waste. As research data accumulate on the adverse impacts of pharmaceutical waste on human health and the environment, application of the precautionary principle becomes increasingly relevant. A rewarding challenge is to find all possible ways to minimize pharmaceutical waste and reduce its harmful nature. Over the long term it would be possible to tackle the problem with reference to where the problem starts, i.e., the use of pharmaceuticals and the product itself. A correct diagnosis and intervention with pharmaceuticals combined with increased surveillance and follow-up will optimize the outcome of the treatment and reduce the chance for leftover medicine. Many elderly people use more than ten prescription drugs simultaneously, and this polypharmacy is an important reason why drugs become unused. With more personalized drug therapies and medicine interventions, and with better characteristics of the API it is possible that less adverse effects may be observed, leading both to better compliance and less unused medicines. Personalized dosing and package size are product design features effectively reducing waste generation.
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Braybrook S, John DN, Leong K (1999) A survey of why medicines are returned to pharmacies. In: Pharm J 263 No 7063. Pharmacy Practice Research Papers: Proceedings of the British Pharmaceutical Conference; Sept 13–15; Cardiff, UK Bronder E, Klimpel A (2001) Unused drugs returned to the pharmacy – new data. J Clin Pharmacol Ther 39:480–483 Castensson S, Riemsdijk J van (to be published) Pharmaceutical dosage forms causing waste problems Ekedahl A (2003) Unused drugs returned to pharmacies – a few patients return a large proportion of unused drugs. J Soc Adm Pharm 20:257–258 Ekedahl A, Wergeman L, Rydberg T (2003) Unused drugs in Sweden measured by returns to pharmacies. J Soc Adm Pharm 20:26–31 European Federation of Pharmaceutical Industries and Associations (2007) EFPIA take back survey 2007. Personal communication European Topic Centre on Waste and Materials Flows (2003) Preparing a waste management plan: a methodological guidance note. [cited 2007 Oct 30]. Available from: waste/plans/pdf/wasteguide_ final.pdf Hawksworth GM, Wright DJ, Chrystyn H (1996) A detailed analysis of the day to day unwanted medicinal products returned to community pharmacies for disposal. J Soc Adm Pharm 13:215–222 Health Care Without Harm Europe (2004) Non-incineration medical waste treatment technologies in Europe. Available from: [cited 2007 Oct 30] Health Care Without Harm Europe (2005) Waste reduction in healthcare services. Available from: http:/ / document&id=1188 [cited 2007 Oct 30] Hospitals for a Healthy Environment (2006) Managing pharmaceutical waste: a 10-step blueprint for health care facilities in the United States. Available from: 41506.pdf [cited 2007 Oct 30] Kümmerer K (ed) (2004) Pharmaceuticals in the environment. Sources, fate, effects and risks, 2nd edn. Springer-Verlag, Berlin, Heidelberg, New York Kümmerer K (ed) (2008) Pharmaceuticals in the environment. Sources, fate, effects and risks, 3rd edn. Springer-Verlag, Berlin, Heidelberg, New York Office of National Drug Control Policy (2007) Proper Disposal of Prescription Drugs. Available from: http://www.whitehousedrugpol [cited 2007 Oct 30] Socialstyrelsen (2004) (Swedish National Board of Health and Welfare) Kasserade läkemedel. Förslag på åtgärder för att minska mängden överblivna läkemedel. (Discarded drugs. Suggested measures for reducing the amount of leftover drugs). Available from: Publicerat/2004/8474/2004-103-12.htm [cited 2007 Oct 30] Sumpter JP, Johnson AC (2005) Lessons from endocrine disruption and their application to other issues concerning trace organics in the aquatic environment. Environ Sci Technol 39:4321–4332

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