21 CFR Part 11

Document issued by the United States Food and Drug Administration (FDA) in August 1997 that outlines the FDA criteria for accepting electronic records and signatures.

absorbance

A measure of how much of the incident radiation that is directed at a sample is absorbed by the sample. Absorbance is defined by the formula A = log10 (1/T), where T is the fractional transmittance.

accuracy

Measure of correctness (contrast with precision)

analyzer

An instrument used for chemical analysis. An analyzer is usually dedicated to a specific type of analysis.

Antaris (Nicolet Antaris)

Thermo's line of FT-NIR analyzers • View Products

background spectrum

A reference spectrum that accounts for the unique optics of a sampling accessory and an instrument. The background spectrum is the result of the output of the source, the response of the beamsplitter optics, sampling module or sample holder, and detector and any atmospheric absorptions inside the analyzer. Sample spectra are ratioed against a background spectrum so that the final spectrum is free of those features.

beam

In an instrument, the stream of infrared light emitted by the source that travels through to a detector.

beamsplitter

A device inside the interferometer that splits the infrared beam coming from the source into two beams of nearly equal energy. Usually one beam passes through the beamsplitter, is reflected from the interferometer's moving mirror and returns to the beamsplitter. The other beam is reflected from the beamsplitter and then is reflected from the interferometer's fixed mirror and returns to the beamsplitter. The recombined beam exits the interferometer, passes through the sample and travels to the detector.

Beer-Lambert-Bougher law

A mathematical law which states that absorbance increases in proportion to concentration:
    A = a b c
    Where:
      A = absorbance
      a = absorptivity (constant)
      b = pathlength
      c = concentration

calibration

1) The process in which the software analyzes a set of standards in order to calculate a method model for predicting component concentrations in or classifying unknown samples. 2) The process in which an analyzer adjusts the digitizers and amplifiers in the main board of an instrument for optimal performance of the attenuator wheel and detector gain.

calibration curve

A method model that is based on two or more calibration standards which contain different amounts of the components to be measured in a quantitative analysis.

calibration model

A mathematical relationship that describes how the spectral data for the calibration standards correlate with the concentration or classification data. See method model.

calibration standard

A standard that is used to create the method model during calibration. In TQ Analyst, calibration standards are also used to calculate a correction curve, if one is specified.

Classical Least Squares

(CLS) A quantitative method in TQ Analyst which looks at many regions of the unknown sample spectrum to find relationships between absorbance and concentration.

classification analysis

To find the standard or class that most closely matches an unknown sample spectrum or verify that the sample spectrum is similar to the spectra in a specified class.

classification method

A TQ Analyst method that finds the standard or class that most closely matches an unknown sample spectrum or verifies that the sample spectrum is similar to the spectra in a specified class. Classification methods are also known as qualitative methods.

classify

To find the standard or class that most closely matches an unknown sample spectrum or verify that the sample spectrum is similar to the spectra in a specified class.

CLS

See Classical Least Squares.

component

A chemical compound or property contained in a sample mixture.

concentration

The amount of a component in a given volume or area.

CoO (Cost of Ownership)

Can be calculated in many, different ways, however, it is generally a measurement that calculates the total cost of purchasing, operating, and maintaining a tool over its lifetime. Often times these calculations will factor in the amount of space occupied by the tool in order to represent the facility overhead in this calculation. The measure also commonly penalizes the tool for downtime. Cost of Ownership measurements are critical parameters in managing and predicting fab operating costs.

correction curve

A zero-order, linear, or higher order polynomial which can be applied to the concentration values calculated by a calibrated method to improve the accuracy of the analysis.

correction standard

A standard that is used along with the calibration standards to calculate a correction curve. Correction standards are not used in calibration.

correlation coefficient

A measure of the linear relationship between two variables. A value of "one" implies that there is a direct linear relationship between two variables. A value of "zero" implies that there is no relationship between the two variables.

cross validation

A technique for validating a quantitative method without using validation standards. A specified number of calibration standards are removed from the calibration set, then the method is calibrated and the new method model is used to quantify the standards that were removed. This process is repeated until all of the calibration standards have been quantified as validation standards.

cross validation standard

A standard or group of standards that are used to validate a method model during cross validation. Cross validation standards are calibration standards that have been temporarily removed from the method model. The temporary model is then used to quantify the removed standard or standards.

cuvette

A rectangular sample container that is typically made of quartz. Cuvettes are frequently used when high accuracy is needed such as when performing quantitative analysis.

derivative

The rate of change of the Y value with respect to the X value. See first derivative.

detector

A device inside the instrument, sampling module, or accessory that produces an electrical signal in response to the infrared beam striking it. Antaris analyzers contain InGaAs (indium gallium arsenide) detectors.

Design Qualification

The process of defining the functional and operational specifications of the instrument and detailing the conscious decision in the selection of the instrument supplier.

Diffuse-reflectance

A spectroscopy technique that measures changes that occur in an infrared beam when the beam interacts with a particulate sample. The radiation alternately passes through particles and reflects off their surfaces. This causes the light to scatter, or "diffuse," as it makes its way through the sample. An output mirror collects the diffusely scattered energy and sends it to a detector in the analyzer. The detector records the altered beam as an interferogram signal, which can be used to generate a spectrum.

Digital signature

An electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified.

Discriminant Analysis

A qualitative (classification) method in TQ Analyst which uses multiple standards that define multiple classes to determine the class or classes of known materials which are most similar to an unknown material. It reports a list of classes ranked from best match to worst match, and a distance value for each class.

Distance Match

A qualitative (classification) method in TQ Analyst which uses multiple standards that define multiple classes to determine how closely an unknown materials matches each class. It reports a list of classes ranked from best match to worst match, and match value for each class.

DQ

see Design Qualification

electronic signature

A computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.

fiber optic cable

A bundle of thin, glass or plastic transparent fibers that are enclosed by a less refractive material. The fibers transmit light by internal reflection.

first derivative

The rate of change of the Y value with respect to the X value. See derivative.

Fourier transform

1) To convert an interferogram (data in the time domain) to a single-beam spectrum (data in the frequency domain) to reveal the response to all frequencies within the spectral range. 2) The mathematical operation used to convert an interferogram to a single-beam spectrum.

FT-NIR

Abbreviation of Four transform near-infrared spectroscopy. A near-infrared spectroscopic technique that uses an interferometer for data collection and a digital Fourier transformation to process the data.

GAMP

Good Automated Manufacturing Practices. A guide to the validation of automated systems in pharmaceutical manufacture.

GC

Gas Chromatography

GMP

Good Manufacturing Practice. United States Food and Drug Administration regulation on the methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing, or holding of a drug to assure that such drug meets the requirements of the act as to safety, and has the identity and strength and meets the quality and purity characteristics that it purports or is represented to possess.

HeNe laser

A Helium/Neon laser. See also laser.

HPLC

High Performance Liquid Chromatography

infrared (IR)

A region of the electromagnetic spectrum extending from approximately 12,800 cm-1 to 30 cm-1.

infrared beam

The infrared light emitted by the source in an infrared spectrometer or analyzer. The beam travels from the source to the detector.

InGaAs detector

Indium Gallium Arsenide detector. See also detector.

Installation Qualification

The process of ensuring that the equipment and ancillary systems are capable of consistently operating within established limits and tolerances.

Integrating sphere

A device used in diffuse-reflectance spectroscopy. When using an integrating sphere, the light beam is angled into the sphere and travels directly through the center of the sphere, through the optical window, and into the sample. Reflected light from the sample re-enters the sphere. An internal detector measures the reflection and sends the information to the interferometer.

Interferogram

The signal produced by the constructive and destructive addition of light when the infrared beam in the interferometer of a Fourier-Transform Infrared (FT-IR) spectrometer or analyzer is recombined.

Interferometer

A device that splits and then recombines the infrared beam in a Fourier-Transform Infrared (FT-IR) spectrometer or analyzer. The output signal is an interferogram.

IQ

see Installation Qualification

ISO

International Organization for Standardization. The source of ISO 9000 and more than 13 000 International Standards for business, government and society.

laser

An internal calibrator in the instrument which emits light at a known and constant frequency. The laser helps control the moving mirror’s position and signals the capture of data. The laser source in the Antaris instrument is a helium/neon (HeNe) laser head.

Log (1/R)

A data format parameter for the Y-axis of spectra in Result software. Log (1/R) units are derived by taking the logarithm of the inverse of the fractional reflectance. Log (1/R) units are analogous to absorbance units used in transmission experiments.

method

A set of parameters and spectra that can be used to create a method model.

method model

A mathematical relationship that describes how the spectral data for the calibration standards correlate with the concentration or classification data.

micrometer

The X-axis unit used for wavelength. One micrometer equals 1 x 10-6 meter. A micrometer is also known as a micron.

micron

See micrometer.

moving mirror

The mirror in the interferometer that reflects the infrared beam back to the beamsplitter while moving toward and away from the beamsplitter in a repeating cycle.

nanometer

An X-axis unit used for wavelength. One nanometer equals 1 x 10-9 meter.

near infrared (NIR)

A region of the electromagnetic spectrum extending from approximately 12,000 cm-1 to 4,000 cm-1.

noise

Random signals produced by electrical or other components in an instrument, which can affect spectral data.

Number Of Scans

The number of times the analyzer will scan the sample to produce a spectrum.

Operational Qualification

The process of demonstrating that an instrument performs consistently as specified by the instrument vendor, by testing critical areas of the instrument, such as data collection and mathematical algorithms. Thermo Nicolet offers the ValPro System Qualification package, which runs a series of workflows that perform operational qualification tests on the Antaris FT-NIR analyzer.

OQ

See Operational Qualification.

Partial Least Squares (PLS)

A quantitative method in TQ Analyst which uses a partial least squares statistical analysis to determine which regions of the calibration spectra vary as a function of component concentration.

PCR

See Principle Component Regression.

peak

A region of a spectrum where the sample absorbs radiation.

peak area

The intensity of a spectral region, determined by finding the sum of the intensity values in the specified X-axis range.

peak height

The intensity (Y value) of a spectrum at a given X value.

Performance Qualification

The routine process of verifying that an instrument is performing according to requirements for the instrument’s intended use.

PLS

precision

Reproducibility. Does not imply anything about correctness of a measurement.

Principle Component Regression (PCR)

A quantitative method in TQ Analyst which uses a principle component regression statistical analysis to determine which regions of the calibration spectra vary as a function of component concentration.

PQ

See Performance Qualification.

Qualification

Stages of the validation process. The qualification process is generally described as having four main phases Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ).

QC Compare Search

A qualitative (classification) method in TQ Analyst which uses multiple standards that define multiple classes to determine which standard and class are most similar to an unknown material. It reports the best matched standard in each class, and a match value for each standard. The classes are ranked from best match to worst match.

qualitative analysis

To identify the composition of a sample mixture.

qualitative method

A method that identifies an unknown sample by comparing its spectrum to the spectra of known materials which represent pre-defined categories, or classes. Qualitative methods are also referred to classification methods.

qualitative model

A method model that can be used to identify the composition of a sample mixture by comparing the sample spectrum to the spectra of known materials which represent pre-defined categories, or classes. Qualitative models may also be used to determine the degree of similarity between the unknown sample spectrum and a given class.

quantitative analysis

To measure the concentrations of one or more components in a sample mixture.

quantitative method

A method that measures the concentrations of one or more components in a sample mixture.

quantitative model

A method model that can be used to measure the concentrations of one or more components in a sample mixture.

ratioing

The process of removing the effects of the instrument and any water or carbon dioxide absorptions (if these gases are not completely purged from the instrument) from a sample spectrum by dividing the spectrum by a background spectrum, or a reference background spectrum, at each data point.

reference

A known component of a sample that is added to a background spectrum in order to remove the peaks caused by the component from the sample spectrum. See also reference background spectrum and ratioing.

reference background spectrum

A background spectrum that includes the spectrum of a reference substance that is a component of a sample. Reference backgrounds are typically used to remove peaks due to known sample components by dividing the sample spectrum by the reference background spectrum. See also ratioing.

Reflectance (%)

A data format parameter for the Y-axis of spectra. Percent reflectance units are normally used to display a spectrum collected using a reflection technique. Percent reflectance shows the amount of infrared energy reflected from the sample.

reflection-absorption

See transflectance.

Resolution

Resolution measures how well closely spaced peaks in a spectrum are differentiated. The higher the resolution, the more separated two closely-spaced peaks will appear. Increasing the resolution requires that the distance traveled by the moving mirror in the interferometer be increased.

RESULT software

Thermo Nicolet’s software for routine spectral analysis. RESULT is comprised of two software applications, RESULT Operation and RESULT Integration. • View Product

RMSEC

(Root Mean Square Error of Calibration). RMSEC is one of the algorithms available in TQ Analyst for calculating the performance index for quantitative methods. The closer the RMSEC value is to zero, the better the method will perform.

RMSECV

(Root Mean Square Error of Cross Validation). It refers to the error of the cross validation process used to determine the recommended number of factors for each component in the active PLS method. RMSECV is one of the algorithms available in TQ Analyst for calculating the performance index for quantitative methods. The closer the RMSECV value is to zero, the better the method will perform.

RMSEP

(Root Mean Square Error of Prediction). The uncertainty of prediction for a component, which is calculated by squaring the error values, calculating the average, and then taking the square root of the result. RMSEP is produced by a Compare event in RESULT Integration software.

SabIR diffuse-reflectance probe

Thermo Nicolet’s diffuse-reflectance probe that can be used with the fiber optic sampling module. The SabIR probe allows you to analyze solid and powder samples remotely. • View Product.

sample

A compound being analyzed.

sample spectrum

The spectrum of an unknown material being analyzed.

Search Standards

A qualitative (classification) method in TQ Analyst which uses multiple classes and one standard per class to determine which known material is most similar to an unknown material. It reports a list of standards ranked from best match to worst match, and a match value for each standard.

second derivative

The rate of change of the first derivative with respect to the X value.

signal-to-noise ratio (SNR)

The ratio of the intensity of a signal to the intensity of the noise that accompanies it.

Similarity Match

A qualitative (classification) method in TQ Analyst which uses multiple standards that define one class to determine how closely an unknown material matches a known material. It reports match value, which indicates the quality of the match.

Simple Beer’s Law

A quantitative method in TQ Analyst which uses the classic Beer-Lambert-Bougher law (absorbance increases proportionally with concentration) to create a method model.

single-beam spectrum

A spectrum (data in the frequency domain) obtained by Fourier transforming an interferogram (data in the time domain). A single-beam spectrum shows the response at all frequencies in the spectral range. A sample single-beam spectrum can be ratioed against a background single-beam spectrum to produce a sample spectrum with the background information removed.

slope

The rate at which an ordinate of a point of a line on a coordinate plane changes with respect to a change in the abscissa (i.e., the rise divided by the run).

SMA connector

An industry standard connector (Sub-Miniature, Type A) used for fiber optic connections. SMA connectors are characterized by a cylindrical sleeve and threaded locking unit.

SMLR

See Stepwise Multiple Linear Regression.

SNR

See signal-to-noise ratio.

softgel tablet analyzer

The Nicolet Antaris tablet analyzer optimized for use with samples that are good transmitters, such as softgel capsules, paper, plastics, packaging materials, and polymers. The softgel tablet analyzer has a broad-band InGaAs detector and covers a spectral range of 12,000 ­ 3,800 cm-1 (833-2,630 nm). • View Product.

SOP

See Standard operating procedures.

source

A component inside an infrared spectrometer or analyzer that emits the infrared radiation that travels to the detector.

spectral range

The range of frequencies included in a spectrum.

spectral region

A portion of a spectrum between two frequencies or wavelengths.

Spectralon

A soft, porous and highly-diffuse sample with high reflectance that can be used as a background reference for diffuse-reflectance sampling.

spectrometer

An instrument for measuring a spectrum. Thermo Nicolet produces FT-infrared, FT near-infrared, and Raman spectrometers.

spectrum

A graphical representation of the intensity of the radiation reaching the detector at each X-axis location measured. The intensity at a given X-axis location is determined by the characteristics of the instrument used to collect the spectrum and the sample, if one is present.

specular reflection

Reflection of light in which the angle of incidence equals the angle of reflection, i.e., "mirror-like" reflection.

standard operating procedures

Written authorized procedures documenting instructions that should be followed for performing operations. SOPs can include general instructions for maintenance and cleaning, equipment operation, and sampling.

standard tablet analyzer

The Nicolet Antaris tablet analyzer optimized for use with dense materials, such as opaque tablets. The standard tablet analyzer has a narrow band, high-sensitivity InGaAs detector, and covers a spectral range of 12,000 ­ 5,880 cm-1 (833-1,700 nm). • View Product.

standards

Known samples that model the behavior of the unknown samples that will be analyzed with a method. For quantitative analyses, standards are samples which have known concentrations of each component the method will be used to analyze. For qualitative analyses, standards are samples that have the characteristic you want to track.

Stepwise Multiple Linear Regression (SMLR)

A quantitative method in TQ Analyst which expresses concentration as a function of the absorbance at specific frequencies.

suspect data

Data in the RESULT Operation audit log that has been marked as possibly being tampered with or incorrect. Suspect data is noted with an asterisk (*) before the Key ID entry in reports created by RESULT Operation software.

tablet analyzer

A sampling module used to collect transmission data of tablets. When connected to the Antaris analyzer, the light beam is directed into the tablet analyzer and through the sample. The amount of light that passes through the tablet is picked up by the detector in the tablet analyzer cover and sent to the interferometer. Antaris products offer two types of tablet analyzers: a standard tablet analyzer and a softgel tablet analyzer. Also see standard tablet analyzer.

three-position cuvette/culture tube holder

The sample holder that is used with the Antaris FT-NIR analyzer transmission module to collect data from samples held in cuvettes, culture tubes, or vials. The cuvette/culture tube holder has three locations (front, middle, and rear) through which collections can be taken, but samples can be collected only from the front and rear positions. The middle position is only for collecting backgrounds without a reference. Also called a sample tube holder.

throughput

The intensity of the infrared energy that reaches the detector in an analyzer.

TQ Analyst software

Thermo Nicolet’s software package for creating, calibrating, testing and troubleshooting methods for measuring spectral data. TQ Analyst provides a wide range of tools for creating quantitative, classification and spectral measurement methods in a user-friendly application. • View Product

transflectance

Also known as reflection-absorption. A spectroscopy technique in which a beam enters the sample, reflects off a reflective surface, and passes through the sample layer a second time. Under many conditions, particularly when studying liquids, the resulting spectrum resembles a transmission spectrum.

transmission

A spectroscopy technique that measures the percentage of light transmitted through a sample.

transmission module

The module of the Antaris analyzer that allows users to collect spectra from liquid samples and transparent solids and films using transmission spectroscopy.

transmittance (%)

A data format parameter for the Y-axis of spectra. Percent transmittance units are normally used to display a spectrum collected using a transmission technique. Percent transmittance shows the fraction of the radiation that remains after a beam of electromagnetic radiation passes through a sample. Percent transmittance is defined by the formula T = (P/P0) * 100, where P is the radiation that passes through the sample and P0 is the radiation when no sample is present.

validation

establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. Both the process and analytical equipment must be validated.

validation standard

A standard that is used to evaluate the performance of a calibrated method. The results from the validation standards are also used to calculate the performance index.

ValPro Qualification software

A software package that includes a comprehensive set of qualification tests, including Pharmacopoeia-recommended tests, to verify instrument performance. ValPro Qualification software works within RESULT Operation software. • View Product.

vial

An inexpensive, cylindrical sample container that is usually made of glass or plastic. Vials are often unsuitable when taking high accuracy measurements such as those involved in quantitative analysis.

The distance between corresponding points in consecutive light waves. Wavelength is measured in micrometers or nanometers.