Due to its polarized composition, water has characteristics that allow it to be used in many ways in the pharmaceutical field. The capacities of absorption, adsorption and dissolution of water make it a versatile material and that is why its use is so widespread in the different pharmaceutical processes.The universal solvent property of water makes its use very popular for the synthesis of active compounds or for their cultivation. Water is also used in the purification steps of drugs. In addition to its presence during the manufacture of various pharmaceutical products, water can be stored for direct or indirect use during the administration of said product to various patients. Finally, it is widely used in the disinfection and sterilization of various equipment.

Since water is of primary importance in pharmaceutical operations and its quality must not be neglected, several international standards have been developed to ensure the quality of the water used and the safety of users. These standards, called pharmacopoeia, are exhaustive works regarding the different products, their methods of use, their composition and any other important information related to them. The three major pharmacopoeias available internationally are those of the United States (USP), Europe (EP) and Japan (JP). Although there are some differences among these pharmacopoeias, the main lines are very similar.

Water categories

Drinking water is a type of water with light treatment from different natural or stored sources. Natural sources can be a spring, a well, a river, a lake, or the sea. Depending on the contaminants present in the original source, the necessary treatment will be adapted to make the water fit for human consumption. Generally, to reach drinking water quality, the classical treatment includes desalination, softening, removal of certain ions, particle reduction and antimicrobial treatment.

Purified water is a higher quality water than drinking water. To be manufactured, purified water must come from a water source of drinking quality or better. Since this quality of water must meet the specifications of the applicable pharmacopoeia, it is important to monitor its chemical and microbiological purity. In addition, this type of water must be protected from recontamination and microbial growth. To achieve the necessary water quality, purified water can be treated using a combination of reverse osmosis, electro-deionization, and distilliation. Other ways can be used to achieve this water quality, but this is the most common.

Furthermore, Water for Injection (WFI) is recognized as the highest quality water for pharmaceutical use. It is a hypotonic solution intended for the preparation of a solution for parenteral administration. To achieve this type of water quality, pharmaceutical companies have access to several types of technologies. The use of double reverse osmosis coupled with other technologies such as ultrafiltration, deionization or ozonation can be one way. Being the ultimate water quality in pharmaceuticals, water for injection must comply with the applicable pharmacopoeias. This often means control of chemical purity and microbiology, including endotoxins, and protection against recontamination and microbiological growth.

Type of treatment

 Since high quality water must be created from potable water, we will briefly discuss the types of treatments that can be used for this step. Depending on the quality of the incoming water, the types of treatment used can vary greatly. Since there is a wide variety of basic treatment available on the market, we will only present the most common technologies.

First, coagulation/flocculation treatments and sedimentation basins are a very interesting option for the reduction of dissolved solids in water. Biological technologies such as aerobic and anaerobic treatments are ideal options for the reduction of biological oxygen demand (BOD) and chemical oxygen demand (COD). Then there are the different types of filtrations. Depending on the water input, filtration is a very effective step in the removal of certain viruses, bacteria, colloids, and many other contaminants.

Advanced treatment

Although the use of reverse osmosis is widespread in many fields, pharmaceutical reverse osmosis has some specificities of its own. Moreover,  when used alone, reverse osmosis is not sufficient to achieve the water quality required to manufacture water for injection. To do so, other advanced technologies must be added.Among these technologies, polishing with an electrodeionizer (EDI) can be used, coupled with other technologies such as ozonation or UV sterilization as well as the use of sterilizing filters with pores of 0.2micron or better to control bacteria. Nevertheless, to learn more about these types of systems, this article presents an overview of pharmaceutical purified water systems "Overview of a Pharmaceutical Purified Water System".

Identification problem

The difficulties of identifying pharmaceutical contaminants is not effortless. Indeed, whether we think of the identification of chemical compounds present in the effluent or their concentration, the variations between production batches make their identification difficult. Then, the origin of the contaminants is even more complex. Obviously, pharmaceutical industrial effluents are an important source of contamination. However, since the source is known, it is relatively simple to solve the problem as best as possible. Moreover, the compounds used are known to the pharmaceutical industry and can be treated on site depending on their nature.

Hospital waste is a more complicated problem because it is difficult to monitor, even though it is subject to biomedical waste regulations. Knowing that the different water treatment technologies all have qualities and flaws, it can be complex to identify the ideal technology for a hospital since the variations in concentration and contaminants are so intense that a system could be ineffective most of the time.

On top of this, the chemical compounds of the drugs used by different groups of people have a significant impact on the contamination of natural environments. When a drug is consumed, the body metabolizes it to make the molecule more polar in order to facilitate its absorption and excretion. Regardless of the route used to leave the body, the metabolized chemical ends up in the environment and very often ends its journey in water.

Difficult treatments

Like everything else, water treatment systems have strengths and weaknesses. That's why there is such a wide variety of technology. Depending on the technology chosen, the effectiveness against certain contaminants may vary.

Generally, municipal wastewater treatment plants are not designed for the treatment of pharmaceutical contaminants. For example, ibuprofen (Advil) is generally removed at a rate of at least 75%, which could be better considering the commonplace and sometimes daily use of this drug. Despite this, the withdrawal rate of Advils is not critical compared to some other molecules. Sulfamethoxazole, a widely used antibiotic, is only withdrawn at an average of 11% by municipal wastewater treatment plants.

Once "treated" by municipal plants, the effluent is then discharged into the environment despite the presence of pharmaceutical compounds. As for the compounds that could be removed from the water, they are generally found in the sludge, which is then deposited in landfills or used as fertilizer on agricultural land.

Obviously, the presence of contaminants in the environment has a strong impact on the organisms in contact with these contaminants. Although the use of sludge on agricultural land is a current and legal practice in Canada, the presence of pharmaceutical contaminants in sludge indirectly affects the efficiency of the land. In addition, it has been shown that long-term consumption of water contaminated with pharmaceutical compounds can have an impact on the human body. These impacts include respiratory problems, reproductive problems, and even chronic depression.

If only the problems related to these contaminants stopped there! But no, the antibiotic contaminants pose an additional challenge. As discussed above, some antibiotics such as sulfamethoxazole are extremely difficult to remove from water. However, this is not the main problem. Continuous exposure to any antibiotic has been shown to contribute to antibiotic resistance. Therefore, bacteria in the water can develop resistance to antibiotics in the same water. Thus, the effectiveness of these drugs can decrease dramatically and increase health risks.

Most common contaminants

Again, depending on the source, the contaminants vary greatly. For example, regarding hospitals waste, a study conducted in Quebec in 2021 identified 10 compounds representing the most toxic and commons contaminants found in the environment. These contaminants are the following:

Next, here is a short list of different contaminants that can come from industrial effluents

Although the data collected is from different locations, such as a hospital in Quebec and a water source located near a pharmaceutical plant in India, the same types of contaminants have been identified in water sources in the United States and elsewhere in Canada.

With more than 850 pharmaceutical compounds and some 12,000 approved drugs, the lists developed above are only the tip of the iceberg and the impact of every pharmaceutical compound in the environment should not be overlooked as they can be just as problematic.

Some possible solutions

Since pharmaceutical contamination can come from industrial effluents, hospital effluents or post-consumer secretions, identifying a solution is a major challenge.

In addition, because municipal treatment plants are not built to handle this type of contaminant, it is important to ensure effective treatment before discharging into local sewer systems or the environment. In many places, governments have intervened to manage the discharge of pharmaceutical effluents. In other places, such as Quebec, legislation is very flexible with these types of contaminants. In fact, in Quebec discharges into local sewers are mainly under municipal jurisdiction. For this reason, acceptance standards vary considerably from one location to another.

Are you interested in industrial wastewater management? Visit this article presenting the different types of discharges, the different legislations, and the possible problems.

Fortunately, social dogmas have been changing for some time and companies are adapting to them. Respect for the environment is becoming a major issue for any company and therefore, despite the absence of obligation, more and more pharmaceutical companies are opting for a more responsible use of water and ensuring a more efficient extraction of contaminants.

Pharmaceutical effluents

In short, the technologies currently used to treat pharmaceutical effluents are extremely efficient and versatile.These technologies allow the optimization of production lines by allowing the reuse of water and the recovery of several by-products such as solvents, acids, heavy metals and several other APIs. The recovery of by-products is usually done during the pre-treatment stage and this step can be very advantageous as it adds a weight of gold in the balance by allowing the recovery of products with a high economic value.

The technological advancement of membrane bioreactors has made them a technology of choice in the pharmaceutical industry. When a biological treatment is adopted, the high retention of sludge offered by these bioreactors and their relatively low cost offers interesting results to the pharmaceutical industry. Indeed, in addition to drastically decreasing the total dissolved solids in water, these bioreactors have proven to be effective against more than 10 estrogens. However, it is important to remember that the complete removal of all pharmaceutical contaminants is extremely complex, regardless of the technology used. This is why pharmaceutical companies often use a combination of technologies during the water treatment process.

On the advanced treatment side, tests that are still being conducted today have identified technology combinations that offer better removal rates. For example, titanium dioxide combined with UV technology and hydrogen peroxide has demonstrated a very effective removal rate against phenol. Secondly, electrochemical oxidation treatments using hydroxyl radicals have demonstrated very impressive removal rates against ethinylestradiol, diclofenac, carbamazepine, propanolol and ibuprofen.

To make a long story short, other advanced treatments such as ultrasound treatment and wet air oxidation also have promising characteristics. Tests are showing increasing efficiencies in the removal and recovery of contaminants from pharmaceutical wastewater. The combination of advanced treatment technologies, called hybrid treatments, seems equally promising towards achieving optimal treatment.

Conclusion

Considering the strong expansion of the pharmaceutical sector and the diversification of the products and by-products used in the process, the technological advancement of water treatment follows the curve without exceeding it. In order to ensure a viable future for our society, it is imperative to identify sources of solutions to reduce the impact and presence of pharmaceutical contaminants in our lives.

Although treatment technologies are becoming more and more diversified and studies are still being conducted to find new solutions, emerging water purification technologies are very often used exclusively for the manufacture of pharmaceutical products. In other words, for financial reasons, effluent treatment systems are rarely as efficient as the initial system. In short, technological advancement must be accompanied by ingenuity, rigor and good will to ensure a clean future for our society. Fortunately, more and more pharmaceutical companies are showing imagination and good faith in their use and discharge of water.

If you have any questions or suggestions regarding this article? Leave a comment below or write to us at: [email protected]

Sources

• Boucher, V. (2021). Élimination des composés pharmaceutiques des eaux de rejets hospitaliers par oxydation par voie humide. (Mémoire, Université Sherbrooke, Sherbrooke).
• ChandrakanthGadipelly, AntíaPeŕez-Gonzaĺez, GanapatiD.Yadav, Inmaculada Ortiz, Raquel Ibań ̃ez, Virendra K. Rathod, et Kumudini V. Marathe. (2014). Pharmaceutical Industry Wastewater : Review of the Technologies for Water Treatment and Reuse. Accessible from https://pubs.acs.org/doi/abs/10.1021/ie501210j
• Harold Schwartz, Lesya Marushka, Hing Man Chan, Malek Batal, Tonio Sadik, Amy Ing, Karen Fediuk & Constantine Tikhonov . (2021). Pharmaceuticals in source water of 95 First Nations in Canada. Canadian Journal of Public Health, 112 (1) 133-153
• World Health Organization. (2012). Bonnes pratiques de fabrication de l’OMS : eau à usage pharmaceutique. Accessible from https://www.who.int/medicines/areas/quality_safety/quality_assurance/FR-GMPWatePharmaceuticalUseTRS970Annex2.pdf?ua=1
• World Health Organization. (2020). Good manufacturing practices : water for pharmaceutical use. Accessible from https://www.who.int/medicines/areas/quality_safety/quality_assurance/QAS20_842_rev1_gmp_water_for_pharmaceutical_use.pdf?ua=1
• United States Environmental Protection Agency. (2014). Pharmaceuticals in municipal wastewater. Accessible from https://www.epa.gov/water-research/pharmaceutical-residues-municipal-wastewater
• Vikas Chander, Bhavtosh Sharma, Vipul Negi, Ravinder Singh Aswal, Prashant Singh, Rakesh Singh, Rajendra Dobhal. (2016). Pharmaceutical compounds in drinking water. Journal of Xenobiotics, 6 (5774).
• Y Guo et al 2017 IOP Conf. Ser.: Earth Environ. Sci. 63 012025