Pharmaceutical Water: A Critical Component in Medicine Production

Water plays a vital but often overlooked role in the pharmaceutical industry. Strict purity standards are required at every stage of medicine production to ensure patient safety. From raw material processing to final packaging, water is used extensively and must meet stringent quality benchmarks. In this article, we will explore the importance of pharmaceutical water, how quality is assured, and new technologies being adopted by manufacturers.
Water Standards for Raw Materials
Nearly all active Pharmaceutical Water and excipients require water during their manufacture. However, normal drinking water is unsuitable due to risk of contamination. Water used at this early stage must comply with compendial standards like those from the United States Pharmacopeia (USP). Key standards include limits on:
- Total organic carbon (TOC) - No more than 500 parts per billion of TOC is allowed to prevent impurities.
- Endotoxin levels - Bacterial fragments known as endotoxins must be under 0.25 endotoxin units per milliliter to avoid toxicity.
- Microbial growth - Heterotrophic plate counts must be less than 100 CFU/mL and total coliforms must be non-detectable to ensure sterility.
Strict adherence to these standards helps protect drug purity from the beginning of the production cycle. Advanced treatment systems reliably produce water that meets or surpasses limits.
Purified Water in Pharmaceutical Processing
Once APIs and excipients are blended and formulated into drug products, highly purified water is needed for manufacturing steps like granulating, coating, washing, and rinsing. Known as Purified Water, it must satisfy compendial specifications for tighter quality control. Key attributes include:
- Resistance - Purified Water should have a resistivity of at least 1 megohm-cm to eliminate ions and dissolved solids.
- Bacterial endotoxins - Levels must be less than 0.25 EU/mL.
- Microbial contamination - Heterotrophic plate counts of 10 CFU/mL or less are permitted.
Advanced purification systems using reverse osmosis, deionization, and ultraviolet treatment reliably output water surpassing USP Purified Water standards for critical production use. Proper system design and operation ensures a infection-free water supply.
Water Quality Assurance
Quality control of pharmaceutical water is of utmost importance. Comprehensive testing verifies treatment systems are working as intended. Major tests performed on a routine schedule include:
- TOC analysis - Measures overall organic compounds to confirm adequate removal down to parts-per-billion levels.
- Bacterial testing - Plate counts check for heterotrophic and coliform bacteria to be non-detectable or extremely low.
- Endotoxin testing - The LAL kinetic turbidimetric test quantifies endotoxins below maximum limits.
- Resistivity measurement - Checks Purified Water resistivity is within tight specifications.
Continuous monitoring with online analyzers also helps catch any excursions between lab tests. Calibration and preventative maintenance keeps water production equipment operating optimally to supply high-purity water meeting strict compendial and internal standards.
Feed Water Pre-Treatment
The starting point for pharmaceutical water production is often the public water supply or well water. However, raw source water may contain impurities requiring pre-treatment before advanced purification. Common pre-treatment steps include:
- Chlorine destruction - Adds sulfite to deactivated residual chlorine in municipal water sources.
- Carbon filtration - Removes trace organic chemicals and chlorine byproducts that RO cannot.
- Iron/Manganese sequestration - Chelating agents complex dissolved iron and manganese that could foul membranes.
- Hardness stabilization - Converts calcium and magnesium to non-scaling salts to protect reverse osmosis.
Proper pre-treatment results in feed water compatible with downstream purification technology like reverse osmosis, thus maximizing system efficiency and permeate quality. It is a critical first step in the water treatment train.
Reverse Osmosis: The Workhorse Technology
Reverse osmosis is used by virtually all pharmaceutical manufacturers to produce high-purity water from pre-treated feed sources. Key advantages of this process include:
- Dependable organic removal - RO effective at reducing TOC to parts-per-billion levels.
- Ion/dissolved solids rejection - Semipermeable membrane rejects ionized and large molecules at high percentage.
- Bacteria/virus barrier - Pore size of 0.0001 microns screens out microorganisms.
- Automation capabilities - RO systems can integrate online analytics and be controlled remotely.
New energy recovery devices are also helping boost RO efficiency. Overall, RO is relied on heavily in the pharmaceutical industry to deliver purified and high-purity “water for injection” used throughout manufacturing. It remains the standard primary purification technology.
Deionization: The Final Polish
While reverse osmosis achieves very high purity water, deionization is often the final step to produce ultrapure “water for injection” meeting stringent standards. Major types used include:
- Mixed bed deionization - Removes remaining ions using cation and anion exchange resins. Generates extremely high resistivity of18.2 megohm-cm or greater water.
- EDI - Features electrodialysis to intensify ion removal from RO permeate for higher quality.
- Column deionization - Flexible columns filled with adsorptive resins provide polishing of various volumes.
Supplemental treatment with activated carbon and ultraviolet may also be included to deliver pyrogen and organics-free water. Proper filtration and regeneration is key to maintaining deionizer capacity and surface purification for the highest quality pharmaceutical water.
With an increasing global demand for medicines, the pharmaceutical industry relies heavily on water of the strictest purity standards during production to ensure patient safety. From feed water pre-treatment through advanced technologies like reverse osmosis and deionization, manufacturers have implemented robust water treatment infrastructures and quality programs to supply purified water for all stages. As medicine needs rise, new treatment solutions continue advancing to provide the high-purity “water for injection” upon which drug manufacturing depends. Pharmaceutical water remains an absolutely critical process component. 

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