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The Value of Water in Pharma Labs

Minimizing water waste can benefit the surrounding human and ecological community

 

Water is a critical element of pharmaceutical manufacturing. Without it, the processes required to manufacture pharmaceuticals, clean the lab and its equipment, ensure the final product quality, and keep manufacturing facilities running would be impeded.

 

The FDA’s regulations for the water used in the manufacturing of active pharmaceutical ingredients (APIs) states that, at minimum, the water should be drinking (potable) water quality. This means that the water used in the manufacturing of pharmaceuticals can come from the tap, but with the following stipulation: “If drinking (potable) water is insufficient to ensure API quality and tighter chemical and/or microbiological water quality specifications are called for, appropriate specifications for physical/chemical attributes, total microbial counts, objectionable organisms, and/or endotoxins should be established.”

 

 

Yet, the US Pharmacopeia has far stricter guidelines for what can be used in the manufacturing of APIs. The US Pharmacopeia is a book containing directions for the identification of compound medicines for the US, and it explains that the drinking water used in pharmaceutical manufacturing must be must be made to pass conductivity and total organic carbon (TOC) requirements for Purified Water (PW), with the additional requirement of passing an endotoxin test for Water for Injection (WFI); PW and WFI are explained to be the two grades of water most commonly needed for pharmaceutical manufacturing.

 

The processes used to get the PW and WFI to meet these requirements can be intensive, since microbiological contamination is a major concern for water used in critical cleaning of pharma equipment. The most commonly used techniques to deal with the presence of bacteria in water include reverse osmosis, electrodeionization and distillation, although ozone has been used as well.

 

Wastewater facilities have the ability to process and clean water of certain substances but are generally not equipped to completely eliminate the presence of all pharmaceuticals from the water supply.

 

Since this process is extensive, following the use of the decontaminated water, the question remains regarding where this water should go. In 2007, the Associated Press brought attention to research conducted that showed the presence of pharmaceuticals in our water supply. What further research into the subject found was that the source for this contamination was the presence of pharmaceuticals in our wastewater. Wastewater facilities have the ability to process and clean water of certain substances but are generally not equipped to completely eliminate the presence of all pharmaceuticals from the water supply.

 

In a paper published by The National Association of Clean Water Agencies (NACWA) and the Association of Metropolitan Water Agencies (AMWA), it explains, “Treatment processes can and do reduce the concentrations of pharmaceuticals in water, however, the degree of efficacy is often a function of chemical structure, cost, and energy. All treatment processes have some degree of side effects, such as generation of residuals or by-products.”[1]

 

The paper goes on to clarify that the question of whether pharmaceuticals are present or not is not the issue, as they are definitely present. It explains that “the application of ultra-sensitive analytical technologies to detect anthropogenic substances in water at one trillionth of a gram or less per liter will undoubtedly reveal that nearly every compound known to man will be detectable.” The question is instead “whether they pose a risk of harm to humans and wildlife that are exposed.”

 

What is concluded in the paper is there are continued uncertainties regarding the presence of pharmaceuticals in the water and its effect on human and ecological health. Research seems to show little effect on humans in general so far in the current amounts present in water, although the effects on wildlife, and specifically fish, have been far clearer.

 

Areas where there is runoff into lakes and rivers have resulted in fish having reproductive abnormalities, such as male fish that grow eggs in their testes due to the presence of female hormones from birth control pills in the water.

 

Ultimately, it ends up being the responsibility of the pharmaceutical manufacturer to decide whether they wish to be a “good neighbor” for their human and ecological community.

 

This presence of pharmaceuticals in wastewater can come from a few different sources. Consumers of pharmaceuticals may urinate or defecate out amounts of pharmaceuticals (since bodies don’t absorb all of the chemicals present), wash their bodies which may have pharmaceuticals on their skin, or even flush pharmaceuticals down the toilet. Yet, the question still remains regarding the role of pharmaceutical manufacturers in the contamination of wastewater. Currently, contamination of wastewater by manufacturers is not an area that is heavily regulated by the EPA, although the EPA does enforce regulations regarding hazardous pharmaceutical waste. Ultimately, it ends up being the responsibility of the pharmaceutical manufacturer to decide whether they wish to be a “good neighbor” for their human and ecological community.

 

And some do make that decision. For some companies, the decision is less humanitarian and more economic, since putting back their spent water into the process to be used again can save money. Joe Manfredi, president of the consulting firm GMP Systems, worked on a project where they “put roughly 35 gal./min. (of 50 gal./min.) of wastewater, which normally would have been sent to the sewer, back into the front end of the system.”[2] Although this costs the company more than if it used municipal water, there is only a limited amount of feed water available for the company to use, causing reuse of the water to become the best choice.

 

For other companies, they use spent water after it is run through another reverse osmosis system “to sprinkle their lawns, run cooling towers, run their boilers or flush toilets.”[3] These systems have the ability to also benefit the company economically, as they can save 15-30% of their regular water usage by using spent water. Ultimately, one of the benefits of this process is that before the water is reused, it is first cleaned, meaning the water is placed back into the environment without the same presence of pharmaceuticals, which the wastewater treatment plants may or may not be able to eliminate if they are solely responsible for the elimination process.

 

Clearly, the decision to reuse spent water is one that is not only sustainable economically, but also more sustainable for the surrounding communities and ecological systems.

 

By Alana Hippensteele, Editor, American Cleaning & Hygiene

 


[1] National Association of Clean Water Agencies and Association of Metropolitan Water Agencies. (n.d.). Pharmaceuticals in the Water Environment. Washington, DC: Author.

[2] Swichtenberg, B. (2007, August 20). Achieving Clean Pharmaceutical Water. Retrieved October 14, 2019, from https://www.pharmamanufacturing.com/articles/2007/130/.

[3] Swichtenberg, B. (2007, August 20). Achieving Clean Pharmaceutical Water. Retrieved October 14, 2019, from https://www.pharmamanufacturing.com/articles/2007/130/.


 

Critical Cleaning Innovations

 

Tougher residues need more effective detergents

 

The biopharma industry, including cosmetics, supplements, botanicals, and more, is ever expanding, ever improving, and ever changing. Whether this means gentler enteric tablet coatings, more effective creams, lotions and ointments, purer botanical extracts and resins, biosimilars, personalized medicine, or hosts of other advances, critical cleaning must rise to the challenge.

 

Critical cleaning, almost exclusively achieved via aqueous detergents, is a level of cleaning that directly impacts the value of the final product. This covers the entire biopharma industry spectrum where drug potency, purity and quality are increasingly scrutinized processes. Analytical techniques have improved, allowing for more accurate and precise cleaning evaluation. Demands for end user and drain safety, biodegradability, water-resource efficiency and other desirable detergent attributes continue as well.

 

Many of these new advances are highly adherent and have difficulty emulsifying residues that often require “elbow grease,” or mechanical action. Stronger detergents can, at times, solve the need for extraneous mechanical energy. This can mean increases in pH, increased rinsing, or other hazardous/undesirable detergent attributes.

 

The innovative answer is to be not just effective, but also end user safe, aqueous, free-rinsing, interfering residue-free, biodegradable, as well as dye, fragrance, brightener, and filming corrosion inhibitor-free.

 

Furthermore, manual cleaning, mechanistically, is far superior to automated cleaning; that which foams emulsifies best. Applied mechanical energy (scrubbing, soaking, sonication or elbow grease) is able to ‘supercharge’ high foaming detergents.

 

However, sometimes high foaming detergents are not the right choice. For example, a 5000 L reactor/holding tank/mixing vessel often uses an automated clean-in-place system. While impingement provides some mechanical energy, when formulated properly, most of the cleaning is done via chemistry. High and low pH balances compensate for fewer usable cleaning mechanisms. Higher (or lower) pH rapid hydrolysis compensates, in part, for less effective emulsifying capability of the low foaming surfactants.

 

The role of water, intrinsic of course to aqueous cleaning, is often overlooked.

 

The role of water, intrinsic of course to aqueous cleaning, is often overlooked. Another characteristic of properly and innovatively formulated detergents is to be not just free–rinsing, but easily and efficiently rinsing. Free-rinsing ensures the surface will be left residue free. When formulated for ease of rinse, valuable time and water cost can be saved.

 

As new compounds or applications arise in the future, scientists will continue to rise to meet the cleaning challenge. New detergents are always on the horizon to ensure even safer and more effective, efficient and complete critical cleaning.

 

By Michael Moussourakis, Senior Director, Technical Marketing and Strategic Affairs, Alconox Inc.