When you are in the process of developing any new analytical technology, having the ability to prove your innovations are as precise and as accurate as you believe them to be is critical. This need for external verification is true whether you are involved in the development of a new protocol, a new assay or a new instrument.
It can be devastating to find out that well before your new invention has reached its limits, the techniques you have access to for testing it have become useless.
This frustrating situation was faced by Mark Wardle, development engineer at SGE Analytical Science, who was involved in creating the award winning eVol® – the world’s first digitally-controlled analytical syringe. The eVol is a marriage of two precision devices: a digitally controlled and programmable electronic drive and an XCHANGE® enabled analytical syringe.
The aim of the project was to develop an instrument that could accurately deliver a requested volume time after time no matter who was operating the device – unlike pipettes where poor operator technique can lead to large variations in the actual volumes delivered.
The eVol more than met the expectations of the development team in reducing the variability of volumes dispensed when different operators attempt the same volume transfer. What’s more, it was also suitable for transferring non-aqueous, viscous and hazardous liquids. The eVol can be fitted with a number of different XCHANGE enabled syringes allowing it to dispense volumes from 1mL down to 200nL.
However, when Wardle was preparing the eVol specification document, he found he couldn’t complete it as he wasn’t able to generate the accuracy and precision data – that is, the proof of performance – he needed at the lower end of the eVol’s dispensing range. While Wardle found that gravimetric analysis of dispensed volume worked for volumes greater than 50 µL, when he attempted to go below this volume this traditional method for measuring volumes did not provide the results he expected.
No matter what he did with the SGE facility’s air conditioning system, the water he was delivering onto the analytical balance evaporated before a stable reading could be accurately determined. In the end, he tried five different gravimetric methods – but nothing worked.
Due to SGE’s expertise in chromatography, Wardle’s team then attempted to use a chromatographic technique to test the eVol’s accuracy. A known volume of an internal standard was added to a test mix, and then dispensed from the eVol. The concentration of the internal standard was then measured via gas chromatography and the accuracy of the eVol calculated. This was time consuming and wasn’t sufficiently accurate. After weeks of trying to develop a chromatographic methodology to a suitable degree of accuracy, the team stopped using this approach and looked around for a technique that they could use to determine the eVol’s accuracy at low volumes.
Next, they explored using a colorimetric method, but efforts were quickly discontinued when they discovered that the plate reader demonstrated an inaccuracy of ±2% – much larger than what the team predicted the inaccuracy of the eVol to be.
Then SGE turned to a fluorescence spectrophotometry method, but despite technical assistance from the instrument manufacturer, their efforts again yielded inadequate confidence in proving the eVol’s performance claims.
All the while, Glenn Clivaz, Director of SGE’s Liquid Handling Business Unit was pushing for data for the specifications document, so that they could launch the eVol and make as many waves in the market as possible.
Despite not having all the data they wanted for the specifications document about the eVol, SGE decided to exhibit their new innovation at Lab Automation 2010 in Palm Springs, CA, before its official launch. While at the show, Clivaz, discovered the Artel PCS® Pipette Calibration System and asked if he could use it to test the eVol – Artel went one better and offered to put a PCS at the SGE booth. To the amazement of the SGE team they could demonstrate the eVol’s claimed precision and accuracy in the exhibition hall –at smaller volumes than Wardle had been able to verify in the SGE labs in Australia.
“The visitors to the booth loved it,” said Clivaz, “They got to play with a great new liquid handling instrument, and because the PCS was so user friendly and scientifically robust, they could test the eVol’s accuracy and precision right at the booth – what’s more they were all getting reliable results!”
The PCS uses Ratiometric PhotometryTM, an innovative application of the Beer-Lambert law which measures the ratio between the light absorbed by a blue dye at 730nm and a red dye at 520nm. This data is then used to calculate the accuracy and precision of volumes dispensed from the liquid handling device.
This ratiometric measurement can accurately determine volumes down into the nanoliter range without needing the controlled environment required for gravimetric analysis – as shown by Artel’s ability to investigate pipette performance in some of the most inhospitable environments in the USA during its Extreme Pipetting Expeditions.
Clivaz was so impressed by the PCS that he wanted to take the instrument back to Australia with him so that Wardle could use it to validate and improve the specifications for the eVol. Artel’s Vice President of Sales, Barry Godowsky was so confident the PCS would enable SGE to finish their specifications document that he happily let Clivaz take a PCS from the booth with him on a sale or return basis. However, Australian customs had other ideas and Clivaz was thoroughly questioned about the PCS instrument as he had brought almost no documentation with him from the show. After a gruelling 3 hours, Clivaz emerged from the customs hall, with PCS in hand.
The next day, Clivaz brought Wardle a present that he would forever remember, and one that would help the eVol win one of the most coveted awards a technology company can win – an R&D100 award. These awards carry so much prestige they are often called the Oscars of Innovation.
On receipt of the PCS, Wardle immediately got to work setting up the system and started getting solid results straight away. He found the PCS very easy to set up and use – he didn’t even need to read the manual, he admits. He was easily able to validate the expected eVol specifications and these were added to the eVol manuals and launch documents.
According to George Rodrigues PhD, Artel’s Senior Scientific Manager, the performance of the eVol is excellent, with the relative inaccuracy of the device at the full-scale values of 500µL, 50µL and 5µL consistently measuring within 0.1%. However, Rodrigues was most impressed with the accuracy and precision with which the 5µL eVol could dispense 0.2µL (200nL): the eVol attained a relative inaccuracy of just 0.41% and a coefficient of variation (%CV) of just 0.71% – this equates to a combined standard deviation for the eVol and the PCS measuring system approaching 1nL .
“Artel has always believed that the PCS was capable of measuring 0.2µL with a standard deviation of 1nL or better, but these were always based on theoretical considerations,” said Rodrigues. “Now that the SGE eVol has been invented, we have the capability of directly demonstrating %CV measurement capability at the 1nL level using an actual liquid delivery device. It’s the perfect marriage of precise liquid delivery and precise liquid measurement.”
To put these numbers into perspective, one of the leading providers of gravimetry-based pipette calibration services, Rainin, quotes a “best uncertainty” of 14nL for a 0.2µL pipette – even under the carefully controlled conditions employed at the Rainin Headquarters in Oakland, California.
The PCS has now become integral to SGE’s further development of the eVol platform and has been used extensively in the development of the latest line extension – a 1mL version that has been requested by many scientists in the NMR field as well as those conducting assays approved by the US Food and Drug Administration (FDA).
Following on from the massive success that SGE had with the PCS, SGE asked Artel to deliver a Liquid Handling Quality Assurance Seminar to train staff in proper manual pipetting technique and assist them in their quest to gain ISO17025 compliance standards.
Doreen Rumery, Artel’s Quality Control Manager, made the 50 hour trip from Portland, Maine in the US to Melbourne, Australia to provide the training sessions. While she was able to provide lots of insight into how the SGE personnel could improve their performance when using standard manual pipettes, she also was amazed at the performance of the eVol.
“Seeing the eVol in action for the first time was a mind-blowing experience. Not only was it so easy to use, but the accuracy the users were getting with it were phenomenal,” said Rumery. “All of the SGE personnel were easily able to get gold medals in our Pipetting Olympics competition using the eVol – something I have never seen before.”
During her visit, Rumery also provided guidance on the steps SGE needed to follow to gain ISO 17025 accreditation so the company can provide its customers with calibration services straight from the factory. Those services would make use of the PCS technology so that all calibrations are traceable to the International System of Units (SI) via top laboratories such as the US National Institute of Standards and Technology (NIST) and the UK National Physical Laboratory (NPL) which further verifies SGE’s claims about the eVol.
“Having access to the PCS gives our sales teams extra confidence in the claims we make about the eVol being the most accurate and precise liquid delivery system on the market,” added Clivaz. And because the Artel technology is so well known and respected, Mr. Clivaz says that SGE is considering putting PCS instruments in all its global sales offices so that customers can test the accuracy and precision of the eVol for themselves.
Keeping a continual focus on optimizing laboratory productivity, particularly in an increasingly global environment, Bjoern has been contributing to the development of international standards for over 10 years. He is a technical expert contributing to the efforts of standards development committees of ISO (International Standards Organization), ASTM International (formerly the American Society for Testing and Materials), and CLSI (Clinical and Laboratory Standards Institute).
Filling a void in testing guidance for users of automated liquid handling systems, Bjoern was one of the industry experts who proposed the development of the ISO International Workshop Agreement (IWA) 15 “Specification and method for the determination of performance of automated liquid handling systems,” serving as project leader and technical editor for the development of this ISO document. He is currently the project leader and technical editor for the development of a series of ISO standards (ISO 23783 parts 1, 2, and 3) slated to succeed ISO/IWA 15.
Bjoern has been contributing as technical expert to the revision of the ISO 8655 series of standards, serving as lead author and project leader for the new Part 8 “Photometric reference measurement procedure for the determination of volume” and project leader and technical editor for the revision of Part 7 “Alternative measurement procedures for the determination of volume.” He is the co-proposer, lead author, and project leader for the development of the new Part 10 “User guidance and requirements for competence, training, and POVA suitability.”
Key Roles:
Project leader for development or revision of:
– ISO 8655-7
– ISO 8655-8
– ISO 8655-10
– ISO 23783-1, -2, and -3
– ASTM E1154
– ISO/IWA 15
Technical expert in:
– ISO/TC48/WG04
– ISO/TC48/WG05
– ANSI US TAG to ISO/TC48
– ASTM E41 and E13
– CLSI
Heidi contributes almost 40 years of Regulatory Affairs and Quality Assurance experience to the Standards Leadership team. Having worked for decades in FDA-registered companies, she is well-versed in FDA regulations, audits, and inspections. As a Certified QMS Auditor, she has been responsible for all aspects of Artel’s ISO 9001 certification and ISO 17025 accreditation processes, as well as the corresponding internal audits. Additionally, she is an expert in industry-specific regulatory requirements, and ensures Artel’s continuous compliance with all applicable regulations and international standards.
Heidi serves as the secretary to the ISO working group responsible for the development of a series of new ISO standards for Automated Liquid Handling Systems, after having provided significant support to the development of ISO/IWA 15. Her standards development expertise is further applied in handling the balloting process of ISO and ASTM standards for the relevant technical committees in the US.
Key Roles:
– ISO/TC48/WG05 – Secretary
– ANSI US TAG to ISO/TC48 – Vice Chair
Responsible for:
– FDA regulations
– ISO 9001 certification
– ISO 17025 accreditation
– Internal audits
– Compliance to RoHS, REACH, TSCA, and others
Richard has been applying his scientific expertise to the development of international standards for over 25 years. He proposed and authored ISO 8655-7:2005 and ISO/TR 16153, based on the ratiometric photometric method for volume determination.
He was an active member in the ASTM International (formerly American Society for Testing and Materials) committee on laboratory apparatus, as well as in NCSL International (formerly National Conference of Standards Laboratories) through the 1990’s. In 1995, he became involved in the revision of DIN 12650 series of standards related to pipettes and other piston-operated apparatus, which led to the development of the ISO 8655 series of standards.
The co-founder of Artel, Richard was company’s original member delegate to the NCSLI – an international metrology association founded at the request of the US National Institute of Standards and Technology (NIST). This close engagement with metrology and measurement excellence was formative in the development of Artel’s measuring systems and laboratory capabilities.
He authored numerous papers and presentations on the topic of pipette calibration, which are referenced in compliance standards, such as the checklists issued by CAP (College of American Pathologists).
Key Roles:
Author of:
– ISO 8655-7:2005
– ISO/TR 16153:2004
– Performance verification of manual action pipettes, Am Clin Lab 1994
– Referenced in CLSI GP-31 A
– Referenced in CAP checklists
– NCLSI member delegate and appointing officer
– ASTM E41 member since mid-1990’s
George has been engaged in international standards and metrology for more than 20 years – working with colleagues at ISO, ASTM International (formerly the American Society for Testing and Materials), CLSI, and NCSL International (formerly the National Conference of Standards Laboratories).
He chairs the ISO working group responsible for the development of the new standard for Automated Liquid Handling Systems, after having co-proposed and chaired the development of ISO/IWA 15, which was published in 2015. He is the former chair of the ISO working group responsible for pipettes and other piston-operated apparatus, where he proposed the development of a new ISO standard for the “Photometric Reference Measurement Procedure for the Determination of Volume” (ISO 8655-8). George is also a technical expert in the revision of all parts of the ISO 8655 series of standards and proposed the development of the new ISO standard on Operator Training and Pipetting Technique.
His deep expertise in metrology is applied in the current revision of the ISO technical report on the estimation of uncertainty for the photometric reference method, numerous articles, as well as across Artel’s product line.
Serving as chair of the US technical advisory group to the ISO technical committee responsible for laboratory equipment, George is responsible for achieving consensus among US experts and articulating this US consensus positions the ISO international technical committee.
George chairs the ASTM sub-committee on laboratory apparatus and serves as secretary to the parent main committee. His metrology expertise was applied in the revision of the balance calibration standards ASTM E898 and E617, which is referenced in the USP (United States Pharmacopeia).
He co-authored the chapters about pipettes and liquid handling processes in the current edition of CSLI QMS-23.
Key Roles:
– Co-author of:
– ISO 8655-7
– ISO 8655-8
– ISO/TR 16153
– Proposer of ISO/IWA 15
– Proposer of ISO 23783-1, -2, -3
– CLSI QMS-23 – Contributing Author
– ISO/TC48/WG05 – Convenor
– ISO/TC48/WG04 – Former Convenor
– ASTM E41 – Secretary
– ASTM E41.06 – Chair
– ASTM E898:2020 – Revision Participant
– ASTM E617:2018 – Revision Participant
– ASTM E1154 – Technical Contact
– ANSI
– US TAG to ISO/TC48 (Laboratoy Equipment) – Chair
– ANSI International Forum – Participant
– NCLSI – Member Delegate & Healthcare Metrology Committee
Kathleen extends Artel’s commitment to using innovative processes for error-free results to Artel’s finance-related activities. Responsible for financial planning and analysis, evaluating strategic opportunities, budgeting, benefits, and compensation, Kathleen uses her long history of doing mergers and acquisitions from a consulting and business side to bring analytical excellence to strategic evaluations, and her experiences at larger companies to advance established processes.
When not at Artel, Kathleen uses all her experience in efficiency and productivity to care for her two daughters and their cat, dog, and horse and, in the very little time left over after that, enjoys travelling to other countries, meeting new people and learning about other cultures.
“Live life as if you were to die tomorrow. Learn as if you were to live forever.” Mahatma Gandhi
Bernadette is the driving force (and friendly face) behind Artel’s content-heavy and customer-centric approach to marketing. She develops marketing/branding strategies and communications campaigns, and leads program execution and analysis by coordinating internal and external efforts, managing budgets, and ensuring consistency and adherence to Artel’s high standards.
Bernie’s strength lies in her ability to reach across all disciplines at Artel—scientific, engineering, metrology, technical support, product development, production, sales, and field support—to make sure that customers are getting the valuable information they need.
Bernie’s passion for detail, quality, and authentic content is expressed in her extraordinary culinary skills, whether the cooking is for an (extensive) family gathering or making a meal for the local community teen center.
“What people do with food is an act that reveals how they construe the world.” Marcella Hazan
John keeps one eye on the latest technologies and another on the challenges facing today’s life science labs. He and his team of eagerly engaged scientists and engineers test new ideas to enhance Artel’s current products and build out tomorrow’s solutions.
Like many Artelians, John is driven by a lifelong curiosity in the physical world around him. He has turned his fascination with spectroscopy and understanding how light interacts with molecules into products that solve real-world productivity and quality challenges for scientists. He was part of the original team that created the MVS and has been involved in product development at Artel since he walked through the front door.
Descended from a family whose motto is probably best expressed as “do a job right, do it completely, and don’t let go until it’s done,” John embodies this philosophy during the day at Artel. He propagates that motto to his kids through gardening, tapping Maple trees and exploring the great backwoods and waterways of Maine.
“It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.” – something Mark Twain may, or may not, have said…probably
Wendy puts her years of experience in the laboratory and her passion for helping people and problem solving to good use as Artel’s Technical Services Manager. Her background has given her hands-on knowledge of customers’ tests and assays, enabling her to understand their pain points since she has experienced them herself. Her goal is to ensure that first-class service is provided by Artel’s customer-facing team, whether it’s directly interacting with customers or through her management of the team. Through hiring, training and guiding her team, she nurtures productive, long-lasting customer relationships.
Wendy’s focus on customers also makes her an excellent internal customer representative to Artel’s teams, where she provides input on product development to the R&D team and communicates any quality issues with Artel products and services to the operations team.
Wendy’s drive to help others resolve problems is not limited to Artel but is evident in all aspects of her life, especially with her children. When not assisting customers, Wendy likes to stay active by biking, boating, and taking long walks in beautiful Maine.
“Nobody cares how much you know until they know how much you care.” commonly attributed to Theodore Roosevelt
Richard combines his scientific education, love of learning, curiosity, and passion for making things work better to build products that help life science labs meet quality and productivity goals. His favorite challenge is finding the bullseye at the intersection of corporate strategy, market need and available technology, and then figuring out how to create a product which hits that target. His leadership has been instrumental in shaping Artel’s products and services into the effective, easy-to-use, and quality-focused offerings that they are today.
When not creating tools and knowledge to help life science labs get the right answers every time, Richard enjoys the great Maine outdoors—canoeing, camping, and gardening—as well as woodworking (usually in the great Maine indoors).
“When you have eliminated every possibility for inaccuracy, then accuracy remains your only option.”
With years of pharmaceutical industry experience centered around analytical chemistry, automation, and new technologies, as well as a background in teaching assay development and validation, Nat’s a natural in his role at Artel as the primary driver and chief communicator of product applications. From optimizing assays, processes, and workflows to pipette user training and calibration, Nat communicates to customers how Artel products and services can improve quality and productivity.
At the same time, he keeps track of key assay trends and applications to inform new product development and strategic guidance for business development, partnering, and collaborative opportunities.
While typically a casual and friendly person at Artel and at home, Nat’s aggressive commitment to quality comes out when he homebrews beer and other fermented beverages and he’s even been known to kick people out of the kitchen to avoid contamination.
“Fast is fine but accuracy is everything.” Wyatt Earp
As a co-founder and President, Kirby’s role at Artel is similar to that of an orchestra conductor—he melds the different elements of the company into a powerful whole, bringing out the best in his colleagues and creating synergies that together overcome customer challenges in liquid handling, quality, and regulatory compliance.
Through a combination of curiosity and discipline, creativity and precision, he works with his fellow Artelians to build outside-the-box solutions that are efficient, easy-to-use, highly effective and based on science. Their goal: to ensure that each customer finds new opportunities and executes new solutions to achieve productivity and compliance objectives.
When not at Artel, Kirby takes up his own instruments, the saxophone and piano, playing for the approval of Charlie Parker and Gabriel Faure.
“Music is your own experience, your thoughts, your wisdom. Master your instrument, master the music. If you don’t live it, it won’t come out of your horn.” Charlie Parker
As the Production Manager, Jim maximizes Artel’s productivity and quality by ensuring that all supplies and components are in place, providing proper training for production personnel, maintaining effective processes, and supporting an overall positive, sound and safe working environment.
Driven by a desire to help others, Jim uses his 30-plus years of experience in the photometric instrument field to ensure that customers know they can rely on Artel, answering questions, solving problems, and guiding them through to complete resolution of any issues they have with their lab’s systems.
Like many at Artel, Jim enjoys cooking and home renovation, and is currently combining his helpfulness and home renovation skills by working on his daughter and son-in-law’s house.
“Seek first to understand, then to be understood.” Stephen R. Covey
An important part of building high-quality products, and providing services that rely on those products, is ensuring that the components and supplies are also high-quality and readily available. Which is why Jack focuses on keeping supply-side relationships top notch. Responsible for the extended supply chain—procurement, purchasing, inventory control, warehousing, shipping, and trade compliance—as well as Artel’s facilities and physical plant, Jack ensures quality by being both a good customer and delivering good customer service.
Jack’s adherence to high standards, quality, and attention to detail are a great fit for his work at Artel and can also be seen in the years-long home renovation project he and his wife have been undertaking. When not at Artel, Jack is an avid traveller, gardener, and connoisseur of cinema and literature.
“No one knows the cost of a defective product – don’t tell me you do. You know the cost of replacing it, but not the cost of a dissatisfied customer.” W. Edwards Deming
Officially, Graham is responsible for overseeing sales, strategic marketing, business development, and applications of Artel’s technology. In practice, this means listening to customers and leveraging his broadly eclectic scientific and business background to identify technological solutions that improve data quality and productivity.
Initially trained as a molecular biologist/protein biochemist, his many years troubleshooting misbehaving assays and analytical methods make him particularly well-suited to a role helping customers with their data quality. The many years at the bench have given Graham a deep appreciation of the importance of reducing sources of noise and variability which, together with experimental controls, can help save weeks and even months of wasted time.
When not at work, Graham’s total embrace of the experimentalist’s spirit is evident in his approach to cooking and baking, also known as “the experiment you get to eat,” which requires precision and tight QC of the ingredients as well as exact execution of the recipe steps to get the desired tasty outcome.
“I often say that when you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind.” Lord Kelvin
With a specialization in metrology and a lifelong interest in both science and engineering, George is ideally suited for his role as Artel’s representative to metrology and standards organizations, laboratory accreditation bodies, and government regulators, where he helps shape regulatory frameworks around liquid handling processes.
These activities give George a deep understanding of regulatory compliance which, coupled with his metrology and quality expertise, he uses to help customers improve data quality and efficiency while maintaining regulatory compliance. This help is especially critical for customers making process improvements, as change can be challenging in regulated environments.
George’s interest in metrology and standards extends beyond his work at Artel (see how he celebrated World Standards Day in 2016). For example, in George’s words, “Deflategate could have been avoided with a properly defined and validated measurement process. With no stated reference temperature, the NFL cannot possibly regulate ball pressure to plus or minus 0.5 psi. A game of inches and seconds, $15 billion annual revenue, and zero metrologists!”
“Every system is perfectly designed to get the results it gets.” Often attributed to W. Edwards Deming, but more likely from Paul Batalden.
As the person in charge of Artel’s Quality Management System, Cary plays a critical role in making sure that Artel’s commitment to quality is always being met. By training employees and keeping all quality processes and procedures well-documented and up-to-date with current regulatory standards she ensures regulatory compliance, and by assessing and evaluating performance both internally and externally (Suppliers) and customer feedback, she supports overall productivity and effectiveness to ensure we meet our customers’ expectations.
When not working closely with her team members to maintain Artel’s quality management processes, Cary enjoys the peace found hiking in the beautiful Maine outdoors.
“Nature does not hurry, yet everything is accomplished.” Lao Tzu
“Random is not one of my strengths.” Doreen Rumery
With a strong work ethic, thorough attention to detail, inquisitive mind that needs to know why things work (or don’t work), and passion for standardization, Doreen is exactly the right kind of person to manage Artel’s chemistry and calibration labs. She’s responsible for making sure the labs run smoothly, ensuring product and instrument quality, calibrations, regulatory compliance, lab personnel training, timely delivery of products, troubleshooting, and process improvements.
Doreen’s need for standardization is apparent even in her home life where spreadsheets and planning tools are used to ensure the household runs smoothly. When not at Artel, Doreen likes to spend time with her family (some of whom she also sees at Artel), gardening, and travelling with her many sisters and brother.
“Quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skilful execution; it represents the wise choice of many alternatives.” William A. Foster
Table 1. Regulations that require demonstration of pipette competency training and/or assessment
ISO Standards | |
ISO/IEC 17025:2005 | General Requirements for the Competence of Testing and Calibration Laboratories |
ISO 15189:201 | Medical Laboratories; Requirements for Quality and Competence |
ISO 15195:2003 | Laboratory Medicine; Requirements for Reference Measurement Laboratories |
FDA cGMP regulations (current Good Manufacturing Practice) | |
21 CFR Part 211 | cGMP for Finished Pharmaceuticals |
21 CFR Part 225 | cGMP for Medicated Feeds |
21 CFR Part 820 | Quality System Regulation for Finished Devices for Human Use |
21 CFR Part 1271 | Human Cells, Tissues, and Cellular and Tissue-based Products |
GLP (Good Laboratory Practice) | |
FDA: 21 CFR Part 58 | GLP for Non-clinical Laboratory Studies |
EU: Directive 2004/10/EC | Principles of Good Laboratory Practice 1997 (Part 1), from the Organisation for Economic Cooperation and Development (OECD) |
GCP (Good Clinical Practice): | |
International Conference on Harmonization (ICH) E6 | Good Clinical Practice – Consolidated Guidance 1996 |