The Davioud laboratory specializes in powder technology. Within less than 10 years it has become a recognized R&D service provider for all major pharmaceutical companies both national and international. The drive to remain at the forefront of technology means it relies on Quantos to precisely control capsule weight. Located in the heart of Eure in France, the Davioud laboratory cultivates origi- nality. It was founded in 2004 by Philippe Davioud a pharmacist and powder spe- cialist with 10 years experience in the pharmaceutical industry. He founded and located his company near his home town in Tillières sur Avre with the in- tention of offering pharmaceutical com- panies unique expertise and know-how, including project management from the workbench to the release of industrial scale batches (clinical batches, pre-clin- ical and small series). Rapid success Less than ten years later, Mr. Davioud has been highly successful. A natural born entrepreneur, his R&D laboratory is inde- pendent and has increased its turnover by a factor of four and its size by a factor of three. It will soon reach 43,000 sq ft and consists of a multidisciplinary team of thirty employees. Mr. Davioud explains, "We offer our customers a 100% inter- nalized study and complete confidential- ity, which is very important in this area. Our structure allows us a flexibility and reactivity which is highly valued by our customers." The laboratory's activities include sup- plier and chemical raw material sourc- ing, processing (active ingredients, micronisation and grinding etc.) and analysis. They also include analytical method development, analytical valida- tion, pre-formulation, formulation (tab- lets, capsules, powders, inhalants, etc.) and the drafting of Part II of AMM files (authorization to sell a drug). 5 News Pharma & Biotech Analytical solutions in the laboratory Quantos Guarantees Capsule Weight Edition 01/2012
Transcript
Weighing and Analysis in the Laboratory
The Davioud laboratory specializes in powder technology. Within less
than 10 years it has become a recognized R&D service provider for all
major pharmaceutical companies both national and international. The
drive to remain at the forefront of technology means it relies on Quantos
to precisely control capsule weight.
Located in the heart of Eure in France, the Davioud laboratory cultivates origi-nality. It was founded in 2004 by Philippe Davioud a pharmacist and powder spe-cialist with 10 years experience in the pharmaceutical industry. He founded and located his company near his home town in Tillières sur Avre with the in-tention of offering pharmaceutical com-panies unique expertise and know-how, including project management from the workbench to the release of industrial scale batches (clinical batches, pre-clin-ical and small series).
Rapid successLess than ten years later, Mr. Davioud has been highly successful. A natural born entrepreneur, his R&D laboratory is inde-pendent and has increased its turnover by
a factor of four and its size by a factor of three. It will soon reach 43,000 sq ft and consists of a multidisciplinary team of thirty employees. Mr. Davioud explains, "We offer our customers a 100% inter-nalized study and complete confidential-ity, which is very important in this area. Our structure allows us a flexibility and reactivity which is highly valued by our customers."The laboratory's activities include sup-plier and chemical raw material sourc-ing, processing (active ingredients, micronisation and grinding etc.) and analysis. They also include analytical method development, analytical valida-tion, pre-formulation, formulation (tab-lets, capsules, powders, inhalants, etc.) and the drafting of Part II of AMM files (authorization to sell a drug).
5News
Pharma & Biotech
Analytical solutions in the laboratory
Quantos Guarantees Capsule Weight
Edition 01/2012
2 METTLER TOLEDO Pharma & Biotech News 5
Publisher Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland
Production Segment Marketing LABGlobal MarCom Switzerland
Keep one step ahead with QuantosSince the beginning of his venture, Philippe Davioud has only one primary goal: to anticipate. In a constantly mov-ing business and scientific world, he is permanently on technology alert; aiming to keep the competitive advantage that makes this laboratory a unique market player in offering its customers tailored solutions to their problems and require-ments.
So, when a pharmaceutical company submits its specifications for the manu-facture of clinical batches, Mr. Davioud searches for the ideal solution. The objec-tive is to guarantee an accurate, reliable and controlled capsule filling process.
Mr Davioud explains, "I thought I had found the right product. Then I discov-ered Quantos and I quickly realized that it was exactly what my clients needed." The Quantos QB1 is a weighing system
ensuring accuracy, automation, security and traceability. The advantage of this product range lies in its capacity of up to 220 g and a readability of 5 µg.
After rigorous testing, the QB1 was quick-ly adopted by the Davioud laboratory where it completes continuous batches of 3000 to 5000 capsules and more if nec-essary. It is also used as a conventional precision balance.
Text: Joël Goursot, Communication Manager,
METTLER TOLEDO France
www.mt.com/quantos
1: Michelle Le Page, R&D laboratory technician, uses Quantos QB1 to ensure a controlled distribution of powders and guarantee the weights in the capsule filling process.
2: Philippe Davioud created his own R&D lab in 2004.
3: The lab features many analytical techniques and is expanding quickly.
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The CCDB is involved in the ‘Interna-tional Barcode of Life’ project, the largest biodiversity genomics initiative ever. Since 2009, the CCDB has processed about 300,000 samples a year from animal, plant and fungal sources. Samples follow a typical genomics workflow with DNA extraction and PCR amplification.
Dr. Natalia Ivanova, Lead DNA Scientist at the CCDB, explains how the Liquidator 96 system plays a fundamental role in the numerous liquid handling procedures re-quired to process her DNA samples.
Fast DNA extractionA typical day involves processing 20 – 40 96-well sample plates. The sample plates
are prepared for robotic DNA extraction using the Liquidator 96. This system en-ables quick and easy, one-handed volume change between steps and its four working platforms are ideal for moving between various sample preparation processes. The instrument is used for adding protein wash buffer during the wash and precipi-tation stages. Finally, it assists with the sample elution to obtain pure DNA for further analysis.
Reliable DNA amplification using PCRFor PCR preparation, 2 μl of extracted DNA sample is dispensed into a pre-made PCR plate containing master mix. Prior to cycle sequencing, the Liquidator 96
More Flexibility and ProductivityIn the Genomics Workflow
Large scale DNA extraction and amplification projects require a multi-
tude of precise and fast small volume dispensing steps. This can either
be done manually or using a robotic system. The Canadian Center for
DNA Barcoding (CCDB) has established its genomics workflow on the
Rainin Liquidator 96, a manual benchtop pipetting system, achieving
exactly the precision and speed that it needs.
See this genomics workflow in action at www.mt.com/Liquidator-CCDB
Find out more about the Liquidator 96 at www.mt.com/liquidator96
Dr. Natalia Ivanova Lead DNA scientist, Canadian Center for DNA Bardocing
"Liquidator 96 system allows you to control the pipetting speed for slow aspiration and dispensing. You can change volumes in a single motion to move to the next step with-out interruption. This prevents introduction of air bubbles and contamination."
system dilutes each sample three-fold and then adds it to the pre-made sequencing plates. It is also used to clean up the PCR product and to remove the dye terminator. The Liquidator 96 system can easily han-dle the small volumes involved and allows you to control aspiration and dispensing speeds.
Text: Nathalie Breuer, Marketing Manager Europe Rainin
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METTLER TOLEDO Pharma & Biotech News 5
Changes in dissolution performance, which are of significant interest in prod-uct quality control, may often occur due to the storage of material at elevated tem-peratures and humidity. Common meth-ods of measuring dissolution endpoints, using UV or HPLC monitoring, provide incomplete information about the tablet dissolution process. Focused Beam Reflec-tance Measurement (FBRM®) can be uti-lized for in situ monitoring of particulates suspended in the dissolution medium throughout the dissolution test. FBRM® provides complementary information about tablet and granule disintegration and dissolution.
Dr. Carrie Coutant, of Eli Lilly and Com-pany, discusses the use of FBRM® in situ particle monitoring for a more thorough analysis of dissolution performance. In this case study, a drug product is known to
Disintegration and Dissolution TestingAssures Drug Product Quality
Dissolution testing is carried out in order to monitor the performance
of oral dosage forms. However, routine testing is often not adequate
enough to fully understand disintegration and dissolution mechanisms.
Innovative testing methods provide a better understanding of how tablet
disintegration and dissolution are affected by changes in the tablets dur-
ing storage.
3.0 buffer 30 C 11 RH4.5 buffer 30 C 11 RH3.0 buffer 30 C 33 RH4.5 buffer 30 C 33 RH3.0 buffer 30 C 65 RH4.5 buffer 30 C 65 RH
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FBRM® detects that tablets stored at a higher humidity disintegrate into larger particles that do not dissolve as readily as the unstressed tablets.
5METTLER TOLEDO Pharma & Biotech News 5
undergo conversion to a less soluble form during storage at high humidity. FBRM® and fiber optic UV detection were applied in order to improve dissolution mecha-nism understanding for the original (un-stressed) tablets and the converted (poorly soluble) tablets.
Innovative Test MethodsTesting was performed using industry standard USP dissolution apparatus II (paddles) with UV and FBRM® process analytical technologies for in situ moni-toring of both the solution phase and the particles in suspension. Method develop-ment experiments were first performed to determine suitable probe position, medium volume, sample concentration, and mixing rate. The effect of the probe on the dissolution profile, as measured by UV, was also evaluated and found to be insignificant under test conditions.
Dissolution testing with fiber optic UV and FBRM® monitoring was performed on ac-tive and placebo tablet materials at a va-riety of media pH. Samples of final blend, uncoated tablets and coated tablets were evaluated to help identify the rate-limit-ing step in the dissolution of unstressed tablets. Active tablets stressed at different moisture levels to induce a range of con-version levels were also tested.
Result: A Better Understanding of Tablet DissolutionMonitoring the disintegration and disso-lution profiles with FBRM® identified an inverse relationship between the amount of drug in solution and the number of large particles that remained undissolved. Solubility of the active ingredient, which is affected by both medium pH and crystal form, impacted the rate of granule disin-tegration and dissolution of the API. Tests
with placebo materials did not detect a significant difference based on storage conditions.
Tablets containing higher quantities of the less soluble form were found to have a different pharmacokinetic performance compared to tablets with higher quantities of the more soluble form.
FBRM® was successfully used for in situ monitoring of tablet dissolution, leading to an improved understanding of product performance. Tracking tablet dissolution helped the characterization of how form conversion impacted dissolution rates and drug availability.
Text: Carrie Coutant, Senior Research Scientist,
Eli Lilly, Indianapolis IN, USA
www.mt.com/formulations
Coating Dissolves/Disintegrates
Tablet Disintegrates
Drug Dissolves Drug DissolvesAqueous Drug
Granules Disintegrate API Deaggregates
Tablet Dissolution and Disintegration Mechanism
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We asked Dr. Matthias Roesslein, senior scientist for measurement uncertainty at the EMPA St. Gallen, Switzerland, to de-scribe the importance of the calculation of measurement uncertainty and its applica-tion into daily practice.
Dr. Roesslein, why is measurement uncertainty important for industries?
Many important decisions are nowadays based on the results of chemical analyses. For example, the results are used to deter-
METTLER TOLEDO Pharma & Biotech News 5
Measurement Uncertainty in TitrationCorrect Result Assessment in Daily Practice
A realistic estimate of measurement uncertainty is crucial for achiev-
ing analytical quality in the laboratory, especially in regulated industry
segments. METTLER TOLEDO, in collaboration with a specialist from
the Swiss Federal Institute for Materials Research and Testing (EMPA),
can offer practical advice on the calculation based on a pragmatic
approach.
Mea
sure
men
t Unc
erta
inty
mine the yield in chemical production processes, to check materials with regard to specifications, or to evaluate compli-ance with a statutory limit. Therefore, companies must provide adequate quality assurance measures, such as validated analytical procedures or accreditation to ISO/IEC/EC/DIN 17025. The aim of all these activities is to document the quality of analytical results by providing a value for their trustworthiness and reliability. In analytical chemistry the measurement
uncertainty proved to be a very useful and, therefore, widely accepted concept to es-tablish the reliability of a measurement.
The calculation of measurement un-certainty is frequently considered as hard to understand and difficult to apply. How is it applied in practice?
For many years, I have worked on the practical application of measurement un-certainty which is best suited for analyti-cal chemistry. The approach is comprised
Editor Dr. Roesslein
7METTLER TOLEDO Pharma & Biotech News 5
Measurement Uncertainty in TitrationCorrect Result Assessment in Daily Practice
of four major steps and focuses on the most influential components in the analytical procedure. In titration, typical compo-nents are repeatability, environmental temperature, consumption to the equiva-lence/end point, and tolerances of mea-suring devices, such as balances, burettes or pipettes. These are comprehensive fac-tors that can be easily obtained, measured and quantified with respective uncertainty values. By applying standard statistical rules, the overall measurement uncer-tainty of the interested value can be easily calculated. For further reference, I recom-mend the literature published in UserCom issues 15 and 16 and the live webinar of-fered on www.mt.com/webinar.
What is the benefit of the measurement uncertainty for an analytical lab perform-ing titrations in quality control?
Provided that systematic errors can be reduced to a minimum, i.e. the complete analytical procedure, including sample preparation and titration, follows a vali-dated standard operating procedure, the percentage contribution of the uncertainty values of the influence factors to the over-
all uncertainty can be derived and appro-priate measures to reduce them can be developed. For instance, if the uncertainty of sample dosing by a pipette is relatively large, higher sample volumes or weighing the sample with a balance should be con-sidered. Therefore, valuable information for improvement of a titration and the analytical result can be extracted. Togeth-er with the profound knowledge of METTLER TOLEDO in titration analytics in the context of Good Titration Practice (GTP), reliable routine analytical results can be achieved.
Dr. Roesslein, thank you very much for the valuable information.
Visit here to download UserCom 15 and 16 for further information:
www.mt.com/AC-UserCom15 www.mt.com/AC-UserCom16
Dr. Roesslein
Dr. Matthias Rösslein is working as a senior scientist at EMPA. He is well-known as a world-leading expert in the field of measurement uncertainty evaluation of analytical chemistry. He has been a member of the Eurachem/CITAC working group on ‘Measurement Uncertainty and Traceability’ since 1997 and has written most of the examples in the guide ‘Quantifying Uncertainty in Analytical Measurement’. In addition, he lectures at different universities covering the topic of measurement science and espe-cially the evaluation of measure-ment uncertainty.
Cause and effect diagram, containing all measurement uncertainties.
8 METTLER TOLEDO Pharma & Biotech News 5
Goo
d M
easu
ring
Prac
tices Good Measuring Practices
For Balances, Titrators and Pipettes
Risk-based lifecycle approach
METTLER TOLEDO, with its
comprehensive Good Measuring
Practices program for titration,
weighing and pipetting, provides
you with a scientific approach to
optimizing your testing efforts. Opti-
mal performance of your laboratory
instrumentation minimizes process
risk and secures internal and exter-
nal audits at all times.
Reduce risk and optimize cost
in just five steps
The five-step guidelines support
you in ensuring compliance with
the requirements of your qual-
ity system at any moment in the
lifecycle of your instruments, and
may significantly reduce the total
cost of ownership of your labora-
tory equipment. The guidelines
begin by evaluating your process
needs, the associated risks and
the regulatory norms of your in-
dustry. Based on this information,
the guidelilnes generate tangible
recommendations for selecting,
installing, qualifying and operating
your instruments.
Thorough analysis
• Evaluate and document the device requirements for current and future applications.
• Identify the limiting factors of your process specifications.
Perfect choice
• Choose the instrument that best fits your process needs to ensure highest accuracy and minimize process risk.
• Select the best option for your after-sales support agreement.
Fast, easy start-up
• Ensure perfect installation and commissioning of instruments.
• Profit from comprehensive user trainings and documentation.
• Ensure consistent and timely calibration and certification.
• Qualify your devices according to IQ / OQ / PQ guidelines.
• Obtain encompassing, trace-able, documentation for quality audits.
Optimized operational efforts
• Define testing and maintenance schemes for your specific pro-cess risk.
• Benefit from our extensive appli-cation database and application support for your daily work.
Step 4: Calibration & Qualification
Step 5: Routine Operation
For more information: www.mt.com/GP
Good Measuring PracticesGuidelines
METTLER TOLEDO’s risk-based guidelines for titration, weighing and pipetting empower you to take the right decision when and where it really matters.
Enjoy every confidence in your process safety and instrument performance day in, day out, knowing that you fully comply with the regulatory norms of your industry.
Good Measuring Practices guidelines satisfy all your needs for quality control and assur-ance, thus providing you with peace of mind at all times.
10 METTLER TOLEDO Pharma & Biotech News 5
Prod
uct N
ews
FastUnderstanding dispersion and diffusion effects is critical when optimizing flow reactions. FlowIR™ tracks these effects in real time to enable stoichiometric reaction control.
Optimize Flow ChemistryWith Real-Time Analysis
Researchers are increasingly us-
ing continuous flow chemistry to
develop new reactions and pro-
cesses with increased specificity,
yield and product quality. Improv-
ing this work is challenging as of-
fline analytical techniques do not
provide the information required
fast enough to optimize the reac-
tion as it happens. FlowIR™ en-
ables the screening and optimiza-
tion of flow reactions in real time
to save valuable time and money
FlexibleOptional flow cell heads provide flex-ibility through heating, various inter-nal volumes and the choice of sensor material to ensure the widest range of chemistries can be studied.
SensitiveMeasurements of sub-millimolar con-centrations without additional service requirements are possible to make the detection of low concentration starting materials, intermediates and products a reality.
Robust and Easy-to-Clean360° free access to the weighing cham-ber simplifies sample handling. The flat surfaces are easy-to-clean. The weighing sensor is completely sealed and spilled samples cannot obstruct the balance.
Ensure valid moisture resultsSmartCal is a granular test substance to check Moisture Analyzers and reliably verifies whether the instrument is work-ing within specifications.
Easy-to-UseReal-time drying curves display each measurement. Frequently used methods are started with One Click™ to make routine work simple and error-free. Indi-vidual user rights ensure quality guide-line compliance.
METTLER TOLEDO offers a variety of publications to keep you and your business up to date and well informed. Our offering includes technical journals, such as UserCom, live webinars giving expert advice and attractive videos via our laboratory YouTube channel. Register now and profit from these tools today.
Application Database Live and On-Demand Webinars YouTube Laboratory Channel
We offer comprehensive applica-tion support for weighing, moisture analysis, titration and many other analytical methods. Our titration application database alone holds over 300 applications for all rel-evant industry segments.
e.g. Titration applications www.mt.com/titration_applications
e.g. Thermal Analysis applications www.mt.com/ta-applications
e.g. Moisture Applications www.mt.com/moisture-methods
Our web-based seminars (webi-nars), live and on demand, give you the opportunity to receive specific and relevant information concerning our products and applications. You can also benefit from our reports on the newest and most advanced methods and standards available.
e.g. Thermal Analysis Webinars www.mt.com/ta-webinars
e.g. Automated Chemistry Webinars www.mt.com/ac-webinars
Experience our range of laboratory products with selected videos from our YouTube laboratory channel. The informative videos offer a com-prehensive overview of our product innovations and application solu-tions.
Watch our videos at: www.youtube.com/mtlaboratory
Novel photovoltaic module technologies made it possible to construct an emission-free airplane and the successful 24-hour flight of a solar powered airplane is no longer just a vision! Solar cells offer a clean and sustainable source of power that demands high standards. Material studies are key features used in the constant improvement of module efficiency and lifetime where water analysis plays a major role.
Solar technology pioneerThe world of solar cells is a broad field with an immense potential for exploration and innovation. The world famous project ‘SOLAR Impulse’, which aims to pilot an airplane around the world solely powered by sunlight, is a challenging task waiting for realization. The official
EPFL (École polytechnique fédéral de Lausanne)Pioneering work in solar technology
Karl Fischer C30
Enhance Solar Cell LifetimeWith Automated Titration Analysis
