THORNTONLeading Pure Water Analytics

Pure Water Analytics for Pharmaceutical Applications

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Mettler-Toledo Thornton's successes in the semiconductor industry helped establish our role as the para-mount worldwide supplier of instrumentation for pure and ultrapure water treatment systems. Leadingpharmaceutical and biotech facilities rely on Mettler-Toledo Thornton instruments to monitor and control theirentire water treatment, storage and distribution systems. Mettler-Toledo Thornton has expanded its capa-bilities to provide state-of-the-art conductivity, TOC, pH, dissolved oxygen and temperature measurementsto meet the current global requirements for pharmaceutical waters. In 2001, Thornton joined Mettler-ToledoProcess Analytics group – gaining world-class technology, global distribution and technical support capabil-ities.

Mettler-Toledo Thornton Industry Participation As a technical leader in pure water measurements, Mettler-Toledo Thornton supports its staff members' participa-tion in the following pharmaceutical and biotech related organizations and conferences:

• United States Pharmacopoeia, Chair, Pharmaceutical Water Expert Committee• Pharmaceutical Research & Manufacturers Association (PhRMA), Advisor• PDA Meetings and Conferences, participant and featured “Industry Expert" • ASTM D19 Water Committee, Task Group Chairman• International Society of Pharmaceutical Engineers (ISPE) & INTERPHEX conferences, active membership, par-

ticipant and featured “Industry Expert” • Ultrapure Water Conference, participant organizer and conference leader

Mettler-Toledo Thornton instrumentation and sensors assure the best available technology to comply with UnitedStates Pharmacopoeia (USP), European Pharmacopoeia (EP), Japanese Pharmacopoeia (JP) and ChinesePharmacopoeia (CP). Validation, verification and service support from Mettler-Toledo Thornton is second to none.

Mettler-Toledo Thornton –leading Pharmaceutical Water measurement.

Mettler-Toledo Thornton – the leader in meetingglobal pharmacopeial requirements

Thornton provides total conductivity, temperatureand TOC solutions to meet worldwide regulatoryrequirements for Purified Water (PW), HighlyPurified Water (HPW) and Water forInjection (WFI). Thornton instruments& sensors exceed all requirements ofUSP <645> Water Conductivity,<643> Total Organic Carbon and2.2.44 Total Organic Carbon andconductivity tests described inPh.Eur. water monographs.

Pharmaceutical water measurement requirementshave been drastically revised in the last decade. Toimprove global manufacturing efficiencies, the UnitedStates Pharmacopoeia developed new requirementsfor Water for Injection (WFI) and for Purified Water,mandating <645> Water Conductivity and <643>Total Organic Carbon tests to replace antiquated wetchemical methods.

USP initiated global HARMONIZATION efforts with theEuropean Pharmacopoeia (EP), JapanesePharmacopoeia (JP) and Chinese Pharmacopoeia(CP) to help bring more consistency to worldwidepharmaceutical water quality requirements. Mettler-Toledo Thornton is positioned as the global leader forHARMONIZATION activities for conductivity and TOCmeasurements.

Conductivity and TOC were introduced as compen-dial tests for pharmaceutical waters originally inUSP 23 Supplement 5 (Nov 1996).• USP <643> and EP 2.2.44 are the principal TOC

compendia that establish limits, system suitabilityand limit of detection requirements.

• USP <645> Water Conductivity and conductivitytests listed in EP water monographs are the princi-pal conductivity compendia that establish limits andcalibration requirements.

Advantages of on-line testing Stage 1:• Real-time process information. Data may be logged,

providing water history• Easy and cost effective in-line measurements• Eliminates sample collection, handling and trans-

portation errors as well as costly Out of Specification(OOS) investigations

• Immediate alarms• In addition, temperature-compensated conductivity

remains an excellent technique to observe waterquality changes for process control

Fundamental Goals for USP Purified Water & WFI• Maintain/Improve existing water quality• Improve the reliability of the testing (using modern

instrumentation)• Reduce the number of tests• Make allowances for on-line, in-line testing• Support PAT initiatives for on-line process control

Pharmaceutical Water –conductivity and total organic carbon requirements.

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Instruments that meet USP Purified Water,Highly Purified Water, and WFI specifications.

Clean-In Place (CIP) and Steam-In Place (SIP) Applications aresome of the most demanding applications in pharmaceuticalproduction. Steam and harsh chemicals are used to clean pip-ing systems prior to use and between batches. Sensors in thisapplication must measure accurately and also withstand contactwith chemical cleaning agents and pressurized steam withoutremoval from the system.

Glassware and cage washers are commonly used inpharmaceutical and biotech research and production to ensurecleanliness of glassware, and sanitary containment for animals.Soap concentrations and rinse water purity are measured forcompliance.

The multi-channel 770MAX and two-channel 2000instrument systems are ideally suited for these vali-dated applications. With two and four-electrodeconductivity sensors installed, these instruments havethe dynamic range to measure pharmaceutical waterand the concentrations of chemical cleaning agents,soap concentrations or pressurized steam. For wash-er applications, a pH sensor can also be used tomeasure soap concentration.

THORNTON 770MAX offers the highest quality and reliability for pharmaceutical and biotechnology water systemsto ensure compatibility and simplicity in calibration, validation and verification of a high purity water system. One770MAX instrument supports:

• Up to 6 multiparameter sensor inputs• Up to 16 measurement types and 8 current outputs• NIST and ASTM traceable standards for all conductivity sensor calibrations• NIST traceable certificates for instruments and calibrators• USP, EP, JP regulation conformance for calibration and performance• Certified 316L electropolished stainless steel sanitary sensors• User-programmable alarm setpoints, pre-programmed USP setpoints for PW

and WFI, and new EP setpoints for PW, HPW and WFI (effective July, 2004)

THORNTON 770MAX optimizes cost-of-ownership with a reduced cost-per-measurement-point, using multiplesensor types with patented Smart Sensor technology connected to one 770MAX instrument. Multiple inputs forany combination of conductivity and/or resistivity, total organic carbon, flow, pH, ORP, dissolved oxygen, pres-sure, level and temperature are possible.

The proven industry leaderThe 200CR, the original member of the 200 series family of conductivity/resistivity, pH, temperature and flowinstruments, offers unmatched performance and value for a wide range of conductivity measurements – especiallyfor USP and EP Purified Water, Highly Purified Water, and Water for Injection applications.

pH for demanding high purity water applicationsThe THORNTON 200pH system includes numerous pH sensors for pharmaceutical and biotechnology waterapplications, plus a high purity pH sensor with a sealed flow chamber to prevent CO2 contamination from the air.

This pH sensor ensures stable performance in high purity water, where CO2 control is essential.

The 200CR features:• One or two channel measurements for a wide conductivity measurement range• NIST and ASTM traceable standards for all conductivity and temperature sensor

calibrations• NIST traceable calibration certificates for instruments and calibrators• USP, EP, JP regulation conformance for calibration and performance• Certified 316L electropolished stainless steel sanitary sensors• User-programmable alarm setpoints, including pre-programmed USP setpoints

for PW and WFI, and new EP setpoints for PW, HPW and WFI (effective 07/04)

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Measuring total organic carbon (TOC)in Pharmaceutical Waters.

• Continuous flow design, no batch measurement cycle• 770MAX Smart Sensor interface• Two TOC Sensors connect to one 770MAX, with four channels remaining for other available sensors• Real-time continuous monitoring for precise data trending and better process control• No gases or reagents to handle, store or replace and no moving parts minimize routine maintenance intervals• Meets USP <643>, <645> and EP 2.2.44 requirements for the Pharmaceutical industry

NEW! 5000TOC SensorWith the addition of the 5000TOC Total Organic Carbon Sensor, the770MAX becomes the first on-line transmitter to offer multiple TOC andconductivity measurements on a user-configurable multiparameterinstrument platform.

The 5000TOC Sensor is designed for all pharmaceutical waterrequirements. Low detection limits, fast, continuous response, and nochemicals are key features meeting industry requirements. The 5000TOCSensor is in compliance with USP/EP TOC and conductivity tests.

Total Organic Carbon (TOC) measurement conformance is clearly defined within the USP <643> and EP2.2.44.as a replacement for the Oxidizable Substances Test. TOC measurements are required to pass specified tests toensure system suitability performance for compliance in pharmaceutical water systems. Thornton InstallationQualification (IQ) and Operation Qualification (OQ) documentation simplifies the compliance process. Thorntonprovides the fastest in-line TOC measurements, without additional chemicals or reagents, to meet globalregulations.

550TOC AnalyzerThe Thornton 550 TOC Analyzer is uniquely designed to provide continuous real-time validated TOCmeasurements in less than 1 minute with 2-second display updates and minimal start-up time and maintenance.

• Accurate, validated TOC measurements for compendial requirements orprocess control – either in-process or in the laboratory

• Truly continuous analysis and rapid measurement updates• Display TOC, resistivity or conductivity and temperature from one unit• No chemicals, reagents, or membranes are required for TOC measurements• Small, portable analyzer• Quick and simple system suitability tests for global regulations compliance

On-Site Instrument Operation &Calibration Training WorkshopsThornton’s Operator Training Courses are tailored toeach customer’s requirements. The course is con-ducted in a classroom setting where interactionbetween instructor and participants is encouraged.Each attendee is supplied with material detailing thecourse content. Instruments are provided for hands-on participation. The areas covered in this trainingprogram focus on Thornton instrumentation,calibration, and maintenance specific to your facility.Additional technical topics may be added orsubstituted as requested.

Traceable Instrument CalibrationThornton offers instrument calibration and validationservices traceable to national standards, industryguidelines, and/or regulatory requirements (includingUSP <645>, USP <643>, and EP 2.2.44). Servicesusing factory-trained technicians are available at ourfacilities in Bedford, Massachusetts or on-site at yourlocation. Each calibrated/validated instrument is sup-plied with the appropriate calibration documents.

Specialized Conductivity CalibrationsChoose one of seven unique conductivitycalibrations to fit your application needs, fromstandard calibrations to customer-specifiedtemperature and ASTM verification points. Systemcalibrations are also available where the instrumentand sensors are calibrated together, optimizingsystem accuracy.

Service & Calibration ContractsA Thornton representative will provide on-site servicefor items covered under the agreement. Theseservices include, but are not limited to:

• Calibration/validation of instrument and sensorsystem

• Issuance of appropriate documentation• Identification and verification of all software

revisions• Minor repairs or adjustment of instruments at a

discounted labor rate• Installation and validation support services• TOC System Suitability Test services

THORNTON Meters

THORNTON Calibrators

Precision Multi-meter

Calibration Lab

National Institute ofStandards & Technology

(NIST)

THORNTON Sensors

THORNTON ReferenceSensors

American Society ofTesting & Materials(ASTM) Solutions

Traceabi l i t y L ineage

Outstanding training and technical servicesempower the Thornton user.

www.thorntoninc.com

info@thorntoninc.comwww.thorntoninc.com

ML0100 Rev.B 07/05

Mettler-Toledo Thornton, Inc.36 Middlesex TurnpikeBedford, MA 01730 USATelephone: +1-781-301-8600Toll-Free: 1-800-510-PURE

Customer/Technical ServiceTelephone: +1-781-301-8690Toll-Free: 1-800-642-4418Cust Service Fax: +1-781-271-0214Tech Service Fax: +1-781-271-0675

© Mettler-Toledo Thornton, Inc. – Subject to Technical Changes

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EuropeMettler-Toledo ThorntonPhone: +49 2066 50 99 057Fax: +49 2066 50 99 058cmaughan.thornton-europe@t-online.de

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ThailandMettler-Toledo Limited272 Soi Soonvijai 4, Rama 9 Rd.Bangkapi, Huay KwangBangkok 10320 ThailandPhone: +662 723 0300Fax: +66 2 719 6479MT-TH.ProcessAnalyticalSupport@mt.com

United KingdomMettler-Toledo Ltd.64 Boston Road Beaumont LeysLeicester, LE4 1AWPhone: +0116 235 7070Fax: +0116 236 5500enquire.mtuk@mt.com

United StatesMettler-Toledo Thornton, Inc.36 Middlesex TurnpikeBedford, MA, 01730 USAPhone: +1 781 301 8600Fax: +1 781 301 8701info@thorntoninc.com

For representation in other countries,please consult our web site.

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Worldwide officesensure prompt, local sales support.