After due consideration in my copious free time, I have reached the conclusion that the world's original scientific instrument was the clock. 

Yes, I know that people have used mirrors since antiquity, and humanity used their eyes to study the world around them (and used their brains to process the information they collected). I know that simple double-pan balances were used to measure masses of various materials. But balances were used as instruments of commerce, while mirrors were used for purposes ranging from vanity to warfare (for example, Archimedes' apocryphal use of a giant mirror or mirrors to set Roman warships ablaze during an invasion of Syracuse, Sicily, in about 214 B.C.). Eyes are natural, not constructed. No, the clock and its predecessors (like the sundial) were probably the first instruments constructed by mankind for the sole purpose of measuring a fundamental scientific quantity: time. 

What is time? We all know what it is, but actually defining it can be tricky. The Merriam-Webster online dictionary defines it as "the measured or measurable period during which an action, process, or condition exists or continues" and "a nonspatial continuum that is measured in terms of events which succeed one another from past through present to future" (1). Some have argued from the perspective of the second law of thermodynamics that time is the increasing of the entropy of the universe. 

Doubtless one of the first recognitions of the passing of time was the day. The repetitious passing of the sun overhead on a regular basis supplied a marker of passing time. In temperate climates, the regular changing of the seasons provided another marker of passing time that eventually became realized as the year. 

The ancient Egyptians usually are credited with the concept of dividing night and day into 12 periods each, called hours. Several reasons have been suggested for using the number 12, including astronomical reasons, the fact that the human hand has 12 phalanges (finger bones — there are three phalanges in each of the four fingers), or the idea that 12 is evenly divisible by 1, 2, 3, 4, and 6. The Sumerians are credited with inventing the sexagesimal (based upon 60) numerical system that ultimately was used to describe the passage of time, in about 2000 B.C. At some point, the division of the day into 24 parts was combined with the partitioning into 60ths and 60ths, so we now adhere to the concepts that there are 60 seconds in a minute and 60 minutes in an hour. 

A variety of physical devices have been used to measure the passage of time since recorded history began. A stick in the ground can be used as a sundial, and burning candles and hourglasses support processes that occur at a constant enough rate that they can be used to track durations. One of the earliest mechanisms to measure time (estimated to go back to about 3000 B.C.) was a clepsydra or water clock (Figure 1), in which a vessel either filled or emptied at some slow, regular rate. Although it was calibrated with a sundial, a clepsydra had the advantage of being usable at night. Good clepsydras were not surpassed in accuracy until the invention of the pendulum clock. 

Figure 1: A clepsydra, or water clock. If properly calibrated, it could mark the passage of time so well that it was not surpassed in accuracy until the invention of the pendulum clock.			

It was sometime in the late 13th or early 14th century when clocks appeared throughout Europe. This was likely due to the invention of the escapement, a mechanical device that regulated the release of energy that was used to drive the clock mechanism. One example is shown in Figure 2. Most early clocks were part of churches, and the ringing of bells as part of the clock mechanism (indeed, the word "clock" comes from the Latin word cloca, meaning "bell") signaled times for religious services or other rituals. Early clocks had no hands. They relied on the number of rings of the bell to signify the passage of time. But by the end of the 14th century, hour hands were beginning to appear, and by 1475, the minute hand could be seen on clocks as well. The first record of a clock with a second hand appeared in 1560, while the first portable pocket watch was invented by Peter Henlein in Bavaria in 1524. 

Figure 2: The escapement is a mechanical device used to control the release of energy in such a way that makes clocks possible.			

Clocks not only were useful in indicating times for religious services. Science used them as well, most importantly in astronomy in order to accurately time the appearances of stars, planets, and moons. The spring-driven clock appeared in the 15th century, and astronomers Tycho Brahe and Johannes Kepler both benefited from the increased precision and accuracy of these new instruments. In 1657, Christiaan Huygens invented the pendulum clock, which was the next big step forward in clock technology. 

Another activity that benefited from improved clock technology was navigation on the oceans. In the days before the global positioning system (GPS), a navigator could determine a ship's position by measuring the angle of a celestial object — the sun or some other notable star like the North Star — and knowing exactly what time it was. Recognizing the need for precision in navigation, in 1714, the British Parliament commissioned the Longitude Prize, a £20,000 prize for a method to accurately determine one's longitude at sea. British clockmaker John Harrison recognized that an accurate clock could be used, and he set about making one. Starting in 1730, over a period of 30 years, he finally developed a spring-driven clock that was accurate to within 10 seconds a day. (Politics, unfortunately, conspired to keep the prize money away from Harrison until 1773, when King George III personally intervened on Harrison's behalf. Harrison died three years later, at age 83.) 

Finally, the Industrial Revolution gave clocks new meaning in several ways. First, it became possible to mass-produce parts so that clocks could be assembled in large numbers, driving their prices down and allowing ordinary people to own them. Second, with increasing employment in industry, employers needed accurate timepieces so they could properly compute hourly wages for their workers. 

Modern clocks have a wide range of energy sources: pendulums, springs, batteries, or other electric sources. They come in analog — with hands — and digital forms. Modern clocks vary in size from a small wristwatch (introduced by Antoni Patek and Adrien Phillipe in 1868) to the 7-m–wide behemoth on the Clock Tower on the Palace of Westminster in London. (The clock itself is not called Big Ben; this is actually the nickname for the largest bell in the tower. While the Westminster Clock Tower is the largest chiming clock in the world, the largest four-faced clock is the Allen-Bradley Clock Tower in Milwaukee, Wisconsin, whose octagonal, 10-m–wide faces light up and can be used as a navigation landmark by ships on Lake Michigan. See Figure 3 for a comparison of these two buildings.) The concept of time is now recognized as a fundamental issue in the natural world, and the measurement and expression of time are crucial to systems like the aforementioned GPS as well as the Internet itself. 

Figure 3: Two famous large clocks. Top: The Allen-Bradley Clock Tower in Milwaukee, Wisconsin, has the largest clock faces for a four-sided clock. Bottom: The Clock Tower on the northeast end of the Houses of Parliament building in London is one of the most famous in the world, and the largest chiming four-faced clock. 			

Science recognizes time as one of the seven fundamental units of nature, and we see time and the need to measure it as an important part of spectroscopy. For instance, the unit of frequency is 1/time, with the unit expressed written as s

  or Hz (hertz). The exact measurement of time is a necessary component of many scientific experiments. 

Why, however, is there an article on clocks in a magazine devoted to spectroscopy? I thought you'd never ask! It turns out that the world's most accurate clocks are atomic clocks, which are based on — wait for it — a spectroscopic transition of cesium atoms. So it turns out that spectroscopy has an intimate relationship in defining time. In the next rendition of this column, we will explore how spectroscopy is used to define time (2). 

 is a professor of chemistry at Cleveland State University in Ohio. Many of his "Baseline" columns have been reprinted in book form by SPIE Press as 

, available through the SPIE Web Bookstore at 

(published in May 2006), is available from SPIE Press. He can be reached at 

(1) The Merriam-Webster online dictionary. Available at http://

(2) The following Wikipedia entries were very useful in researching this column: time, clocks, second, minute, hour, escapement. Available at http://

Articles

Columns: The Baseline

After due consideration in his copious free time, columnist David Ball comes to the conclusion that the world's original scientific instrument was the clock. This might provoke a question: What does it have to do with spectroscopy? The answer might surprise readers.

The Original Scientific Instrument

There has long been a debate in the scientific community on the effect that learning and using a second language has on the brain, as many have wondered whether the brains of bilingual people are different from monolinguals, as well as if bilingualism could possibly have a negative neural effect on young children. Until recently, the proper technology did not exist to properly map and study certain areas of the brain with precise clarity. But thanks to breakthroughs in near-infrared spectroscopy (NIRS), researchers at Dartmouth College in Hanover, New Hampshire, have discovered areas of the brain that indicate bilingualism. Their findings show that the human brain's language centers are enhanced in a bilingual individual as compared to a monolingual individual. 

The Dartmouth research team.  Left to right: Dr. Ioulia Kovelman (Post-doc), Dr. Mark Shalinsky (Post-doc), Professor Laura Ann Petitto (Scientific Director)  Seated: Dr. Melody Berens (Post-doc)			

The authors of the study included Mark Shalinsky, former postdoctoral fellow at Dartmouth, now at Harvard Massachusetts General Hospital; Ioulia Kovelman, formerly a Dartmouth graduate student and currently a postdoctoral fellow at MIT; Melody Berens, currently a postdoctoral fellow at Dartmouth; and Laura-Ann Petitto, the study's senior scientific director, and professor and chair of the Department of Education at Dartmouth. The study was funded by grants to Petitto from the National Institutes of Health and the Dana Foundation. They utilized NIRS techniques with a Hitachi ETG-4000 NIRS system to delve into the higher cognitive capacities of the human brain, hoping to uncover the brain's functional differences between bilingual and monolingual subjects by measuring changes in the brain's oxygen levels while the subjects were tested on their language and cognitive skills. The subjects of the study consisted of 20 people ages 18 to 30, split up into 10 monolingual and 10 bilingual groups.  

What the research team discovered was that when the bilingual subjects were using each of their two languages concurrently and quickly moving between them, both the left and right hemispheres of the brain's Broca area showed an increase in activity, especially in the right equivalent of Broca's area and the right dorsolateral prefrontal cortex. This discovery has shed light on the effect of bilingual language processing on the human brain, proposing that monolingual individuals are not taking full advantage of the brain's neural landscape for language and cognitive processing. 

Dr. Melody Berens hooked up to the Hitachi ETG-4000 NIRS system.			

According to Dr. Petitto, these findings would have been virtually unattainable without the use of state-of-the-art NIRS methods. "Unlike fMRI, NIRS is quiet, small, and, crucially, NIRS tolerates movement. This last feature is especially extraordinary as it lends itself ideally to the study of language, both on the tongue in spoken languages and on the hands in signed languages," Dr. Petitto says. "Typically with fMRI the subject cannot move, making the study of human language, especially the production of the jaw movements in human language and speech, especially challenging. Additionally, both the depth of recording and the temporal resolution of the NIRS system are ideal for studying language, per se. Indeed the new Hitachi ETG 4000 NIRS system is particularly well suited to the scientific study of language." 

The Dartmouth team believes that their research opens up new pathways for NIRS brain imaging technology by performing studies of the brain previously deemed impossible. Dr. Petitto states that fMRI inhibits brain study in infants because they cannot physically be placed in the scanner. However, with new developments in NIRS technology, it is possible to identify and track neural development in newborns over time, potentially unlocking the mysteries of the developing brain. 

The test subjects performed identical language processing tasks in "monolingual mode" (in Spanish, and in English) or in "bilingual mode" (simultaneously processing and quickly switching between their two languages).			

In addition to answering scientific questions about the brains of infants, the Dartmouth team asserts that with advancements in NIRS, researchers will be able to detect atypical patterns of development earlier than ever before. "One day, this new information, in turn, can contribute to intervention plans to help children well before contemporary programs would have provided help. One example is children with developmental language problems who are typically not diagnosed until around ages 3 to 5. Presently, with our NIRS machine, we can encounter a young baby 'at risk' for having language processing delays well before they are uttering their first words, or even babbling," Dr. Petitto notes. "Such early detection can one day lead to early intervention during 'sensitive periods' of brain development when the child is most able to use and benefit from particular types of environmental training over others." 

Dr. Petitto also believes that a decade from now, brain research using NIRS will bring scientific breakthroughs as more scientists and researches will have access to the ever-growing technology. "There is no doubt in my mind that there will be an explosion of Cognitive Neuroscientists who will turn to NIRS as a new window into the formal study of higher cognition, in particular, especially higher cortical functions. I predict the field will indeed embrace this new technology. It is just a matter time before those struggling with the enormous, expensive, and highly finicky fMRI machines turn and embrace the many benefits of NIRS," Dr. Petitto says. "If we just take NIRS and its possible uses vis-à-vis language study, in addition to providing advances in basic research, I can easily see NIRS one day being in every pediatrician's office as part of his or her 'tool kit' of devices that will help doctors identify babies who may be at risk for later language processing disorders. For example, in our laboratory we have observed that very young babies who are typically developing process phonetic and syllabic units in a highly specific swatch of tissue called the superior temporal gyrus as young as three months old – and possibly earlier." 

Dr. Pettito continues, "We have also seen babies at this age who show atypical recruitment of this STG tissue and, if it were my child, or my patient, a prudent suggestion would be that the child may be at risk for learning aspects of natural language. It might also suggest optimal remediation for the child, even one who is quite young. For example, the child may not be perceiving the bite-sized sound nuggets, the syllables, that make up words, or may not be able to parse the constantly varying speech stream to find the key phonetic units and their patterns of arrangements, and thus miss the 'stuff' from which we build all the words in our language." 

Spectroscopy editor Brian Johnson discusses how, by using near-infrared spectroscopy to examine the human brain's higher cognitive capacities, researchers at Dartmouth College have discovered areas in the brain that indicate bilingualism. Their goal is to unravel the mystery of how a bilingual person enhances the brain?s language centers as opposed to a monolingual person.

End of the Spectrum: NIR Speaks a Second Language

Fourier Transform Near Infrared (FT-NIR) spectroscopy is the most recent addition to laboratory NIR technologies. This technological advancement is heavily utilized in the most modern and fastest growing industries, examples of which include pharmaceuticals and biotechnology. 

FT-NIR spectrometers utilize interferometers, which split the source light. One beam is reflected off a fixed mirror, while the other is reflected off an oscillating mirror; the two beams are then recombined, creating an interferogram, to which a Fourier Transform is applied to produce a spectrum. There are several advantages of FT-NIR instruments over conventional dispersive NIR instruments. Given that FT-NIR instruments measure the entire spectrum simultaneously, they are faster, and more sensitive, with lower noise levels.  The inherent design of an FT-NIR system also provides for an internal calibration on every scan, which is known as Conne's advantage. 

The pharmaceutical industry is the leading user of FT-NIR instruments, due in large part to Conne's advantage, which eliminates inter-instrument variability and allows for easy transfer of methods and calibrations between instruments.  This is critical to all functions, such as quality control, research & development, and coordination with process instrumentation. The food industry is the second largest user of FT-NIR instrumentation, with much of its demand derived from the large installed base of conventional dispersive NIR systems that have long been used in that area. The worldwide market for FT-NIR instrumentation will be around $74 million in 2006, and should continue to see annual average growth of 6% to 8% over the foreseeable future. 

The foregoing data were extracted from SDi's market analysis and perspectives report entitled 

Edition Global Assessment Report, 9th Edition: The Laboratory Life Science and Analytical Instrument Industry,

 September 2006. For more information, contact Stuart Press, Senior Consultant, Strategic Directions International, Inc., 6242 Westchester Parkway, Suite 100, Los Angeles, CA 90045, (310) 641-4982, fax: (310) 641-8851, 

Departments

Fourier Transform Near Infrared (FT-NIR) spectroscopy is the most recent addition to laboratory NIR technologies. This technological advancement is heavily utilized in the most modern and fastest growing industries, examples of which include pharmaceuticals and biotechnology.

Market Profile: FT-NIR

In the last column (1), I outlined a suggested process for the integration of equipment qualification and computerized system validation for a spectrometer. In this column I would like to describe how this process should be used in practice with a near-infrared (NIR) spectrometer and computer system for the identification of raw materials in a manufacturing environment.  

Let's start from the beginning through to the release of the system for operational use to understand the process in more detail. I did not cover the need to specify the defined use of the instrument and associated software and computer system in my last column, so we'll start the discussion from this point. (I'm also assuming that you have not already purchased the instrument and been using it for some time.) As always, you'll need to modify and adapt this process to your specific situation.  

The first part of the integrated analytical instrument qualification–computerized system validation journey is writing the user requirements for both the instrument and the software to document the system's intended use. Therefore, you must define the following items and document in the specification document for the system. (Note: I'm not using the word "instrument" quite deliberately for many of the items below and in the rest of the column.) 					

The intended use of the system: In our NIR spectrometer example, the system will be used for the identification of raw materials in a goods inwards facility; therefore, we will consider a qualitative mode of operation only.

Instrument operating parameters: Some of the considerations are to define the operating range of the instrument in region of 750–2500 nm. What resolution will be required of the instrument to be able to discriminate between different samples that might have similar structures? How will the spectra be acquired: in the instrument or using a probe? Automatic sample carousel or manual measurement?

Sample presentation: How will samples be presented to the instrument? This needs to be discussed and debated before the system is purchased. Document in the user requirements specification (URS) the sample type (solid, liquid, or semisolid), container type, and measurement mode (reflectance, transmittance, diffuse reflection, or transflectance). Will measurements be made manually, or will there be automation? The decision will depend on the expected numbers of samples to be identified.

Spectral acquisition, review, and storage: Define what is required here for the use of the system. How will the sample spectra be acquired? How will you store and manage the spectra? For identification, you might not require the sophisticated chemometric tools that a quantitative system would need; therefore, a more basic set of requirements should suffice — but you need to define them.

Library: The instrument will need to acquire and manage spectra used to identify the raw materials. Will there be a single library, or will you need more than one library depending on the discrimination of the instrument or the type of products made within the facility?

System positioning requirements: Will the instrument be located in the laboratory or will it be placed in the warehouse?

Security and access control: Who will be using the system? The needs of the various users will require appropriate access controls. The main users of the system will need more basic user privileges compared with the system manager and a user who can import spectra into the library. Security might not just be around the computerized system, but might also pertain to physical security if the system is placed in a warehouse. Does the system need to be locked in a specific room?

21 CFR 11 requirements such as backup and recovery of the library, sample spectra, application software, and the operating system: Will electronic signatures be used by the operator and the reviewer of the results? 

Interfacing requirements: Will the system be standalone or be connected to the company network? Will data be transferred from the spectrometer to another computerized system such as a laboratory information management system (LIMS)?

Regulatory requirements for NIR spectrometers: The European Pharmacopoeia (2) and United States Pharmacopoeia (3) need to be taken into account both in the initial specification of the system as well as in the qualification tests for the instrument. The two chapters are too long to summarize here, so I will only refer to them as needed, but please keep them in mind as we go through the overall process. However, there is one gem in the European Pharmacopoeia on data storage: "store the electronic NIR, libraries and data according to the current regulations." As you can see, this is very specific (2).

Let's face facts — if you get this part of the life cycle wrong, you will be buying the wrong system. No discussion and no debate. But most people will ignore this advice and just purchase the system. However, if you have not adequately defined your initial requirements correctly, you'll waste money. Also, if you have not thought the problem through well enough, there might be issues when it comes to operating the system. For example, in the outline specification above, the system is being used for a qualitative function. What would happen if you wanted to use it in a quantitative mode as well? Would the same system be suitable? Think things through first and document the requirements in the URS. 

Fast forward to when the purchased system arrives at your laboratory. OK, I've missed the boring bits like initial vendor selection, the delights of reading misunderstood responses to your URS, hands-on evaluation of the short listed systems, and justification of the final system choice; but the emphasis of this column is the integration of instrument qualification with computerized system validation.  

You'll recall from my last column (1) that the process that I outlined consisted of the following five steps: 					

Component installation: Installing the instrument components and the hardware and software for control, data acquisition, and analysis.

Component integration: Integrating the components into the system and showing that they communicate together.

Vendor commissioning: Confirming that the whole system works correctly, including a holistic test of the overall system.

Defining user ways of working: Calibrating and qualifying the instrument over the operating parameters specified for the laboratory, configuring the software for the laboratory and user base, and where necessary, customizing software for specific working practices such as macros.

User acceptance: Conducting system tests to demonstrate the intended purpose, specific software tests, and an overall capacity test if appropriate. These tests should be based upon and traceable back to the documented user requirements.

I'll deal with these two stages as if they were one to save some repetition. These are typically the responsibility of the vendor and must be carried out by them if your warranty and service contract is to be valid; however, it also means you are not wasting your time trying to get the system to work. The process starts from unpacking the instrument and installing it in the location where it will operate. To save time, money, and wasted effort, you will of course install the instrument where it will be used operationally, won't you? 

The vendor service engineer or representative will unpack the components and check that each one is undamaged. The components will be installed by following a written plan provided by the vendor, and the engineer will confirm that each portion has been adequately completed by completing the document. In the event of errors, the engineer will resolve these before completing the installation of a component. For the instrument, the unit will be taken out of the box and positioned on the work bench where it will operate. The instrument should be connected to the power and checked to make sure that it turns on OK. If a sampling probe or autosampler is part of the overall configuration, these items will also be installed by the engineer with appropriate documentation.  

After the instrument is installed, the computer is installed followed by the application software. For ease of discussion, I am assuming that only one application is required. The installation of this must also be adequately documented by the vendor. If the workstation is supplied by the vendor, it might come preinstalled with the operating system, typically Windows. Alternatively, if the system is to be connected to the company network, the company IT department might supply a workstation with the appropriately configured operating system preinstalled. Regardless of the source of the workstation, it can be connected to the network and given an Internet Protocol (IP) address and other information for it to connect and store data on a network drive. Regardless of who does the work, the fact that it was done must be recorded in a compliant manner. Then the application software will be installed by the engineer; again, this will be performed and documented in a procedure that will be completed on site together with problem resolution.  

When completed, the instrument and the computer system will be connected and checked out to see that the two communicate as expected by the vendor. In outline, this completes what should be done in the first two stages of the work. Most, if not all, will be performed by the vendor's engineer and will be adequately documented. It is also the laboratory's responsibility to ensure that the work is recorded in a compliant way and that the work is of a suitable scientific soundness to comply with current good manufacturing practices (GMP) regulations (4). The system owner will review this work and approve it. 

This stage can either be a separate activity after the component installation and integration or it can be combined with them in a continuous session to make it simpler for the engineer to complete. If the latter approach is taken, the process will be from unpacking the individual components to showing that the complete system works and is acceptable from the vendor's perspective. As mentioned above, the instrument and software should work and there should be a holistic test for the overall system.  

Here you should be vigilant and work smarter rather than harder. What is the vendor doing here? Are there tests that are carried out and that can be used instead of you doing the work in later stages of the process, or are there holes in the package? In this instance, you need to do more work later. Therefore, review critically what the vendor proposes to do here and cross check against the system requirements in your URS. Where the vendor's material matches your requirements, then accept this and do no further work. The problem is that you may be reviewing a standard document produced by the vendor to meet most uses of the system. Therefore, in our example of an NIR spectrometer used for qualitative work, what would your reaction be if the vendor proposed to execute tests for quantitative analysis? These tests for the way the spectrometer is intended to be used are probably as much use as a chocolate teapot.  

An example that the vendor could undertake here to confirm instrument operation could be to run some of the certified or standard reference materials to demonstrate that the instrument is correctly calibrated for its intended operation. Some of the parameters include wavelength accuracy, photometric linearity, and noise. It is important that the noise of the instrument is included either here or in the user testing because the instrument performance tends to degrade over time, and therefore it is vital to monitor the overall performance.  

If these tests are not performed here, the users should undertake them during the next phase of the integrated qualification and validation. For example, if a wavelength calibration standard used by a vendor does not offer sufficient resolution or wavelength range, then alternative sources should be used in the next phase by the laboratory. To illustrate this point, Figure 1 shows an example of a wavelength standard over the convention NIR range; more information about traceable standards in NIR will be found in an article to be published in 

Figure 1: NIR wavelength accuracy standard for 890â2540 nm (5,10). 			

Review the proposed tests for the software that the vendor proposes to execute as well. What areas of the software do they propose to check out, and do the tests they will run match your working practices? Will the tests be performed on the unconfigured application, or will the vendor configure this to meet your needs? Look at these carefully. If there is extensive testing on the basic installation, this might have little value if you subsequently configure or customize the software in the next phase of work. On the other hand, if these tests match your requirements, then you'll have less to do later because you have already tested some of your requirements. However, in my experience, the tests performed by the vendor typically will be on the unconfigured software and you have to make a judgment on how useful these will be against your requirements.  

In addition to the instrument and the software, a vendor could provide a standard holistic test to show that the whole system is working as expected. This should exercise both the instrument and the software but should not be exhaustive. It is merely used to demonstrate that everything works as expected. 

Here is where the existing guidance from AAPS Analytical Instrument Qualification (6), USP <1058> (7), and GAMP Forum systems good practice guide for validation of computerized laboratory systems (8) all fall down — they only concentrate on one side or the other of the qualification–validation equation. As I have been advocating (1,9), we need an integrated and systems-based approach to the whole issue or regulatory holes appear in our work. To focus solely on analytical instrument qualification to the exclusion of computerized system validation or vice versa is essentially wrong.  

In this portion of the work, define and configure how you will use the whole system. This may consist of one or more of the following items: 

Qualify the instrument for the operating parameters specified in your URS. Reiterating my earlier point, if the vendor has done this work already and it covers your operating parameters adequately, why repeat this? However, if your ways of working differ from the standard approach, then this is where you will plug the gap and qualify the instrument for your laboratory's specific operating parameters. This is risk management in practice — albeit in an ad hoc form. 

Calibrate the instrument. Again, this takes the same point as above. If it has been done to an acceptable standard over the operating ranges that you intend to use the system, do not do any more work because you'll be wasting time. Alternatively, you know the drill by now. 

Configure the software and firmware. We'll focus here on the software for our qualitative use of the NIR. The main work will be configuring the security and access privileges and setting up the library.  

At a minimum, you'll need to define the user types and the access privileges associated with each type (this will be documented because you'll be testing this in the next phase of the work). Therefore, not all users will be system administrators — unless the user base is very small (for example, two users). In addition, each user will need to have a user identity and password to access the system; every user needs a unique identity so that they can be identified within the system including the audit trails. Most importantly, any default user identities should be disabled and default passwords changed. 

For our qualitative use of sample identification, we will need to establish a spectral library. Therefore, we need to know the following. What compounds will you be sampling? Do you want to organize one library or more? How will you acquire spectra (consideration of wavelength range, number of data points per spectrum, and spectroscopic technique) and how will you treat the spectra before you import them into the library? Who will be able to create entries in the library? You'll need about 30 spectra from different batches of the same material to create the library and the samples should not be too old for inclusion in the library. Much of this work will need a standard operating procedure (SOP) to document how to do this, along with the associated training. The library might need to be prototyped before the building of the library; perhaps only a proportion of the substances to be identified will be entered before the user acceptance testing prior to operational release. In this case the library will continue to be built after the system is live under the control of the library SOP discussed above. 

Customizing the software can include writing macros to reduce the amount of input work a user needs to perform to custom software for interfacing the NIR system to another application such as a LIMS if a standard interface does not exist. For the purposes of this discussion, there will be no customization of the software. This has several advantages: it is faster (no additional work to do), cheaper (same reason), and lower risk (you are not writing unique code that you will have to maintain).  

Focus on Quality

Columnist Bob McDowall takes an NIR spectrometer through the process outlined in his November column, in which he suggested an integrated approach to equipment qualification and computerized system validation for spectroscopy systems.

Spectroscopy-12-01-2006

The Original Scientific Instrument

End of the Spectrum: NIR Speaks a Second Language

Market Profile: FT-NIR

Validation of Spectrometry Software: Applying an Integrated Approach to Equipment Qualification and Computerized System Validation