Weighing and Analysis in the Laboratory

2News

Pharma & Biotech

Recording every measurement and relevant activity within Farmasierra’s

quality control lab, is a complicated and challenging job. Thanks to the

direct integration of METTLER TOLEDO equipment into the company’s

LIMS system, the lab is now functioning as a completely electronic and

paperless environment while remaining fully regulation compliant.

Quality is the utmost parameterFounded in June 1996, Farmasierra, based in Madrid, Spain, is a group of companies whose mission is to offer a global service of manufacturing, distri-bution and marketing of pharmaceuti-cal products, testing everything from raw materials to end products. The imple-mentation, tracking and monitoring of quality is a key function of the quality control laboratory ensuring that prod-ucts and services comply with the quality parameters demanded by regulatory and sanitary authorities.

Farmasierra uses a variety of equipment from METTLER TOLEDO in order to measure weight, density and refractive index and to carry out potentiometric and Karl Fischer titrations. As instruments

in the lab are constantly running, the issue of correctly recording every mea-surement and relevant activity within the entire quality control laboratory is a critical and challenging task and one the company was interested in automating and managing completely electronically.

Going paperlessJose M. Senra, head of the quality control laboratory at Farmasierra, approached METTLER TOLEDO in order to find a solution, which would integrate their instruments into the laboratory network and directly transfer captured data into their LIMS system (Laboratory Infor-mation Management System). His goal was to avoid paper documentation and manual calculations and datasheets in order to manage data more efficiently

Analytical solutions in the laboratory

A Paper-Free Laboratory

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Publisher Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland

Production Segment Marketing LABGlobal MarCom Switzerland

Subject to technical changes. © Mettler-Toledo AG 08/10Printed in Switzerland.

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and to reduce data transcription errors. A portable PDA was chosen as commu-nication device between the instruments and LIMS. The PDA communicates with the LIMS through a wireless antenna in-stalled in the laboratory where it receives electronic daily tasks and work-lists. The analyst carries out the given analysis then the instruments send all data di-rectly to the LIMS, therefore completing the analysis job.

In order to fully integrate METTLER TOLEDO’s instruments into this labora-tory network, a dedicated solution for each instrument line was chosen:

The LabX titration software, in combi-nation with the LIMS connect software module, transfers titration data directly into the LIMS system. All other instru-ments, such as the laboratory’s Semi-Micro Balances XP205, HG63 Halogen Moisture Analyzer, PB1501 Precision Balance, a PB3001-S Precision Balance,

RE40 Refractometer and a DE45 Density Meter are coupled via a special commu-nication port to the laboratory network.

With the LIMS and the portable PDAs in place the quality control lab now works entirely without paper, lab notebooks or data sheets. Thanks to the direct data capture data reliability, accuracy and safety have been improved. In addition, the system offers real time information about any lab instrument and user, sta-tus, data process analysis or batch ap-proval.

The safety and control of all operations has been improved through the imple-mentation of electronic signatures with a fully comprehensive audit trail detailed and secure enough to comply with all regulations.

Three years after implementing the LIMS, the Farmasierra Group has become a pioneer company in the acquisition,

management, evaluation and approval of their analytical data through wireless PDA and coupled communication ports. The analyst only has to prepare samples according to the information given on the PDA, the equipment then analyzes and the LabWare® LIMS system man-ages, calculates, saves and backs up ev-erything without the need for paper.

www.mt.com/LabX

Farmasierra Pharmaceutical plant in Madrid, Spain. The LV11 automatic charger is connected to a precision balance and port communica-tion Lantronix. Capturing data with PDA.

Automatic Titrators are connected to the com munication port. The file is sent out from the METTLER TOLEDO LabX software to LIMS.

3METTLER TOLEDO Pharma & Biotech News 2

Improved accuracyThe customer is always seeking to improve the quality of the products they manufac-ture and continually strives to go above and beyond what is necessary in order to always produce products superior to their competitors. Therefore, it is of the upmost importance to have state-of-the art equip-ment in their laboratories.

One of the quality control labs focuses on the quality of syringes and blood vials be-ing manufactured. They were using com-petitor balances to measure to the fourth decimal place and were finding that mea-surement repeatability was inconsistent. Their dissatisfaction with current meth-

ods led them to call a METTLER TOLEDO sales representative.

The representative installed a METTLER TOLEDO Excellence Plus (XP26) balance as a demo unit. The XP26 offers a capacity of 22 g with 0.001 mg readability. These balances are ideal for weighing small samples directly into the tare container, as they allow very low minimum sample weights. Sample transfer errors can be avoided with adjustable MinWeighDoor and ErgoClip resulting in significant cost savings particularly when using valuable materials.

After using the unit for several weeks, the customer did not want to return it because the quality of results was significantly su-perior to what they had been used to. They were thrilled by the accurate and repeat-able fourth-place readings and decided to keep the demo balance and order two additional XP26 balances to replace all of their current equipment.

Meeting ISO requirementsThe lab was also pleased that METTLER TOLEDO calibrated all of their balances with ISO certified reports. They not only decided on this service for the balances in the QC lab, but in every business area within the company. This was a service

Readability to the Fourth Decimal Place

Since 1897, a METTLER TOLEDO customer has been improving drug

therapy, enhancing the diagnosis of infectious diseases and advancing

drug discovery across the globe. Their quality control lab was troubled

by the inconsistency of measurement repeatability from competitor’s

balances until they discovered METTLER TOLEDO.

that they were not receiving through the competitor.

Our customer now feels confident they are obtaining very accurate measurements. They appreciate their new balances so much, that they have decided to order six more before the end of the year.

www.mt.com/xp-analytical

XP26 Analytical Balance

ErgoClip positions and fastens tare vessels to enable quick and secure direct dosing of samples.

MinWeighDoor is the top choice for weighing small amount of precious samples.

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METTLER TOLEDO Pharma & Biotech News 2

A tricky taskA customer needed to determine the mois-ture content of lyophilized samples con-taining about 60 mg of a very expensive drug with an expected moisture content of 2%. They had previously enlisted a con-tract lab to do their testing, but results were not as expected and even irreproduc-ible and inaccurate. Furthermore, each sample needed up to a week from being sent to the testing lab until the results where communicated. This was obviously not sustainable so the customer decided on an in-house solution to not only save time and money, but also help them re-main in better control of their processes. They then contacted METTLER TOLEDO.

After learning the needs of the client, a C30 Karl Fisher Coulometric Titrator was brought in for a demo. For this type of sample, the traditional technique recom-mends dissolving the lyophilized samples with a very dry solvent and injecting an aliquot of this solution into the titrator vessel. A solvent blank also had to be run

with this then taken into consideration in the final result. During the demo, it was discovered that this technique was prone to mistakes, time consuming and general-ly difficult to master. A difficult challenge for the customer as this would require in depth training for several users. On top of that, the customer wished to weigh 60 mg to meet MinWeigh regulations, produce accurate and reproducible results and re-ceive IQ/OQ/PQ certification.

METTLER TOLEDO’s solutionFirstly, METTLER TOLEDO solved the training issue by reducing the number of steps in the process. Instead of the tra-

ditional method, the sample was directly transferred into the titration vessel. In or-der to do this, the end user dislodges the sample stuck to the small lyophilisation vial wall, tares the sample on a balance, quickly opens the titration vessel, transfers its content in the titration vessel, starts the titration and finally weighs the empty vial back on the balance. While there are still risks involved in the new process, the bene-fits are much more advantageous. With minimal training, a user could master the technique after only a day.

An integral part of this process was ad-dressing a humidity level issue that the

Coulometric Titration the Time and Money Saver

Time and money are of the essence when dealing

with expensive drugs. How does one achieve high

reprodu cibility, save money, develop a technique

that requires little training and maintain regulated

results? In this case, it couldn’t be simpler with

a C30 Karl Fischer Coulometric Titrator from

METTLER TOLEDO.

5METTLER TOLEDO Pharma & Biotech News 2

METTLER TOLEDO expert pointed out could interfere with the reproducibility and accuracy of the result. In fact, add-ing 60 mg of 2% moisture-containing sample means about 120 µg of water in the titration vessel. The influence of ambi-ent humidity has to be minimized due to the titration vessel being opened in order to introduce the sample. The customer managed to lower the ambient humidity in the lab, enabling them to run about 50 samples per day in the same titration vessel before having to replace the Karl Fischer reagents - landing reproducibility at about 2%.

A six place balance was introduced to the lab which satisfies regulations and, upon installation, an IQ/OQ was performed where the customer received pertinent in-formation relative to the tests conducted by the factory trained service engineer.

In the end, METTLER TOLEDO improved the customer’s working conditions by pro-viding a coulometric C30D Karl Fischer

www.mt.com/karl-fischer

titrator. This not only saved money by keeping the analysis in-house, but a six decimal balance also helped them meet MinWeigh requirements. Finally, the sug-gestion to lower ambient humidity greatly improved the reproducibility and accuracy of results. At 50 samples a day, the custom-er is well on their way to saving analysis time, training time and money.

A six place balance helps to meet MinWeigh requirements.

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Performance verificationHisun is China’s leading raw material drug manufacturer and one of China’s largest antibiotics and antitumor drug producers. Due to global expansion, they face increasingly frequent audits by domestic and international regula-tory authorities. With a growing R&D department and expanding production

METTLER TOLEDO Pharma & Biotech News 2

Good Weighing Practice™

for Optimized Weighing Processes

Accurate and reliable measurements are crucial elements in any qual-

ity system. Testing and maintenance of weighing equipment should

be optimized to reduce costs. By choosing Good Weighing Practice™,

a validated global weighing guidelines from METTLER TOLEDO, Hisun

Pharmaceutical Co.’s weighing process is improved and yet fully

compliant to regulations.

facilities, weighing requirements are also increasing along with the need to define a strategy for weighing equipment perfor-mance verification.

Sensible selection programMETTLER TOLEDO’s senior sales engineer, Jin Haiqing, introduced Yang Heyou, QC department manager,

Goo

d W

eigh

ing

Prac

tice™

Good Weighing Practice™ (GWP®) based on Hisun’s specific weighing applications and requirements. GWP is a guideline for the evaluation, operation and testing of weighing apparatus. It does not only ensure measurement security and save costs, but also provides clear advice for practical implementation. For example, in the QC lab of Hisun, testing processes

Yang He (left), QC manager and Jin Haiqing, METTLER TOLEDO senior sales engineer.

7METTLER TOLEDO Pharma & Biotech News 2

should be performed in accordance with the United States Pharmacopeia (USP) for drugs to be exported to the US.

An XP series balance and accessories, which meet with both Hisun’s weighing requirements and the USP requirements, were chosen based on GWP guidelines. This system fully complies with Hisun’s QC requirements regarding frequent use, strict routine testing and regulation stan-dards whilst helping to avoid potential weighing risks.

Efficient routine testingIn addition to recommending the correct weighing equipment, GWP also provides clear guidance on performance verifica-tion. With a GWP assessment, METTLER TOLEDO helped Hisun to further improve and optimize routine testing frequen-cies and test weight management. User SOP’s outlining the correct testing proce-dures, appropriate test cycles, applicable weights, grades and test tolerances helped considerably to ensure that Hisun avoids unnecessary testing whilst minimizing weighing risks.

Through GWP, METTLER TOLEDO is a valued supplier, but also a trusted part-ner for all measurement needs and is currently ensuring that Hisun’s qual-

www.weighingrisk.com

Tips & Tricks

GWP® Risk Check – 5 minutes for your security

Risk Check is a free tool based on Good Weighing Practice™ providing instant expert advice for quality, laboratory and ma nufacturing managers in the Pharmaceutical industry, relying on accurate materials weighing to produce consistent results.

To check the fitness of your weighing processes, simply answer eight questions and the GWP® Risk Check will provide instant expert advice on how to optimize quality systems.

ity control procedures better meet the world’s varying regulations. As a result of the combined efforts of Hisun’s QC and metrology departments, plus the effective implementation of GWP, a total of 22 of its products have passed FDA authentication while 21 have passed EU COS authentica-tion. In the meantime, an additional 20 or more products are under declaration. Thanks to GWP, Hisun’s future is bright.

www.mt.com/GWP

8 METTLER TOLEDO Pharma & Biotech News 2

Onl

ine

Tool

s Seeing is BelievingWatch the Video and Convince Yourself

Common lab dilemma

The multimedia gallery demonstrates innovative solutions for even the most challenging weighing process in your lab. The unique product features and innovative accessories guarantee efficient and ergonomic sample handling.

Our solutions

Disturbance of electrostaticYour sample sticks to the tare container due to elec-trostatic charging and and the balance won’t stabilize.

Anti-static kit – discharges samples instantlyThe U-Electrode remove charges from samples and tare vessels immediately. Toxic substances no longer pose a threat to the user and cross-contamination of samples is prevented.

Spillage of precious samplesYou use weighing paper to transfer precious sample to a tare container. The sample is easily spilled and results are inaccurate.

ErgoClip – doses samples securelyThe ErgoClips safer dosing method substantially reduces con-tamination risks, enables fast dosing processes and increases productivity.

Handling of toxic chemicalsYou’re handling harmful chemicals and want to avoid direct contact.

Solvent Manager – handles chemicals safelyThe Solvent Manager increases operator’s safety in the lab by ensuring that direct contact with harmful chemicals is avoided.

www.mt.com/lab-AntiStatic

www.mt.com/ergoclips

www.mt.com/ titration-solventmanager

9METTLER TOLEDO Pharma & Biotech News 2

METTLER TOLEDO's product finders in mt.com provide a straightforward way to find a product best matching your needs. Just key in your specific criteria and let the product finders do the rest.

Take the direct route to what you are looking for

EasyFinder™ finds your balance of choiceChoosing the right balance for your lab becomes straight forward. Simply enter your selection criteria, select the mod-els of interest and learn more about and/or compare details of the chosen models.

www.lab-balance.com

Sensor product guide foroptimized measurementThis interactive and animated tool helps you to identify the most suited sensor for your specific application.

www.electrodes.net

Find a NewClassic balance in just 30 secondsJust enter your technical criteria and the quick search guides you through a variety of NewClassic models. Click on the product’s picture to learn about the product in detail.

www.mt.com/newclassic

10 METTLER TOLEDO Pharma & Biotech News 2

Prod

uct N

ews Quantos Automated Dosing

Expands Modern Analysis

The innovative Quantos QX1 and QB1-L significantly improve perfor-

mance in analytics, such as UHPLC, as they take care of a very critical

step – sample preparation. The new systems automatically take care of

weighing, sample clean-up and dilution reducing sample quantities by

up to 90%, dramatically reducing the use of solvents, such as acetoni-

trile. Consequently, users are protected from hazardous substances and

products from possible damaging contamination.

Fully automated QX1Tiny sample sizes of as little as 1 mg can be prepared in accor-dance with USP guidelines in a concentration of up to 1:10,000 and within 1% accuracy.

Compact version: QB1-LCompact instrument for sample preparation of powdery and non free-flowing substances thanks to the integrated analytical balance.Liquids are automatically added. www.mt.com/quantos

Precise micro liquid dosingThe revolutionary technology of micro powder dosing with an ultra precise micro-dosing system for liq-uids achieving an extremely precise sample preparation.

11METTLER TOLEDO Pharma & Biotech News 2

Liquidator Fills 96 WellsQuicker and Easier

Liquidator fills 96 wells at once and is an effective 

alternative to complicated robotic systems. No elec-

tricity, computer programming or software is required

making it an ideal solution for cellular assays, ELISA 

and other enzyme based essays or for PCR applica-

tions where the dispensing of PCR buffers and mas-

ter mix preparation is required. Liquidator 96 is com-

pletely portable and can easily be moved between

labs and benches. 

96 and 384-wellsQuick formatting changeLiquidator 96 is ideal for genomic, proteomic, and cellular assays. A 96-well plate can be loaded in seconds and a 384-well plate in only four passes.

96 wellsQuickly filled96 wells can be easily filled in less than 20 seconds with Liquidator 96. Liquidator 96 is faster than all other manual pipetting methods and even many robots.

All Wells Precisely filledRainin Liquidator LTS tips guarantee absolutely consistent pickup. Whatever the dial is set to is exactly what is picked up in the tip with no variability between channels. All wells are filled with exact-ly the same sample volume every time.

www.mt.com/liquidator

Spotlight on Promotion

www.mt.com/lab-pharmaFor more information

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Offer is valid until December 31, 2010.

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