COMPENDIAL WATERS IN INTERNATIONAL PHARMACOPOEIAS

Water is employed as ingredient in many processes, formulations and products. The International pharmacopoeieas (USP, Ph. Eur., JP) define as “Water For Injection” only the compendial water used as an excipient to parenteral solutions. ISPE Glossary distinguishes

– WFI in bulk: “Water for the preparation of medicines for parenteral administration when water is used as a vehicle”;

– Sterilized WFI: ” (Water) for dissolving or diluting substances or preparations for parenteral administration before use”.

The finished water meets all the chemical requirements for PW (Purified Water). With an additional bacterial endotoxin parameter, is the specific WFI character. Since endotoxins are produced by microorganisms that are prone to spread in the water, the equipment and the procedures used by the production lines to purify, store and distribute WFI must prevent the build-up of endotoxin and minimize microbial contamination in the system.

 

DISTILLATION IS THE MAIN WAY TO PRODUCE WATER FOR INJECTION (WFI)

The main metod of WFI production is distillation; most pharmaceutical WFI is produced by this system. Ph. Eur. pharmacopoeia admits only distillation as a method for producing compendial Water For Injection. USP pharmacopoeia admits also a “purification process proven to be equal to or superior to distillation”, while JP pharmacopoeia admits, in addition to distillation, the reverse osmosis (RO) plus ultra filtration (UF). However, all three pharmacopoeias pose the same limit for the endotoxine level (0.25 euml), for TOC values, (ppb ≤ 500), for the bacterial load (<10, Colony-Forming Units / 100 mL) and for the value of conductivity (1.3 µS/cm@25°C). 

 

WATER FOR INJECTION IN BULK*

PHISICAL / CHEMICALPh. Eur.USP
AppearanceColorless, clearNot defined
Conductivity≤ 1.1  μS/cm@20°C≤ 1.3 μS/cm @25°C
TOC ≤ 0.5 mg/L  0.50 mg/L
Nitrates NO₃≤ 0.2 ppmNot defined
Aluminium  10 ppbNot defined
MICROBIOLOGICALPh. Eur.USP
Bacterial count≤ 10 CFU/100 ml≤ 10 CFU/100 ml
Bacterial endotoxins< 0.25 IU/ml< 0.25 EU/ml

*update: January 31, 2021

 

Source: EMA/CHMP/CVMP/QWP/496873/2018. Release: 13 November 2018. Note that the finished water meets all the chemical requirements for PW (Purified Water). And, with an additional bacterial endotoxin parameter, the water meets the specific WFI character. Since microorganisms that are prone to spread in the water produce endotoxins, the equipment and the procedures used by the production lines to purify, store and distribute WFI must prevent the build-up of endotoxin and minimize microbial contamination in the system.

 

There are two basic technologies, that have marked the history of the pharmaceutical industry: the Vapor Compression (VC) distillation system, by vapor compression stills, and the Multiple Effect (ME) distillation system, by multi stage stills.

The FIRST advantage of Vapor Compression is a higher energy efficiency  (low cost by quantity produced) (see our related site: vapor-compression-distiller.com).

The FIRST advantage of Multiple Effect distillation is less moving parts  (with lower maintenance requirement).

 

MULTIPLE EFFECT VS VAPOR COMPRESSION TECHNOLOGY

PARAMETERSMULTIPLE EFFECT DISTILLERVAPOR COMPRESSION DISTILLER
OUPUT FLEXIBILITYReduced  output modulationCapacity ranging from 0 to max.  cap. of the still
TEMPERATURE FLEXIBILITYWFI output 85÷99°CWFI output from infeed water T + 10°C till 99°C
HEATING MEDIA FLEXIBILITYIndustrial steam or electricityIndustrial Steam and/or electricity
COOLING WATERHigh consumption depending on quantity of columnsNo cooling water required
FEED WATERSI02 < 1 ppm, amines free resins (in case of DI), double stage  RO preferredSI02 <30 ppm, Single stage RO or even softened water acceptable
FEED WATER INPUTMust be higher than primary steam pressure< 1 bar
WFI OUTPUTAtmospheric pressure1 / 1.5 bars
PREVALIDATION  (endotoxin challenge)YesYes
HEAVY METALSFreeFree + elimination of chlorine solvents
MOVING PARTSFeed pumpCompressor, Recirculation pump
PURE STEAM FROM 1ST COL.PossiblePossible
STRESS CORROSIONVery high. “Rouging” percentage higherVery low
CLEANABILITYMore tough than VCDMore easy than MED
START UPSCADA (15 min for steam heatingSCADA (15÷40  min, for steam heating)

Multiple Effect – Vapor Compression – COMPARISON TABLE © Bram-Cor 2021 – Data can change without notice