FTIR Spectrophotometer Operation and Calibration SOP

In short: This illustrative SOP covers FTIR operation, performance checks, cleaning and recordkeeping for a QC laboratory. Use the current applicable pharmacopoeial chapter and product method for acceptance criteria; instrument-specific steps (for example Bruker ALPHA-E), calibration frequency and handling instructions must be confirmed against the installed instrument and approved site procedures.

Objective

Provide a controlled template for the operation, performance verification, maintenance and cleaning of a Fourier-transform infrared (FTIR) spectrophotometer.

Scope

Adapt this template to the installed instrument, accessory, software and approved product methods. Instrument-model and software-specific steps (accessory changes, start-up tests, log-in and file handling) are not given here: follow the manufacturer’s manual and the site’s approved procedure, use individually authorised access, and preserve original data and processing history.

FTIR measurements may use transmission or attenuated total reflectance (ATR) modes. The applicable monograph or validated method determines the sample preparation and test conditions. Where Ph. Eur. 2.2.24 applies, the current revision reduced the transmission wavenumber-scale check from seven to four positions and gives separate position values for ATR. The EDQM identifies this revision as Ph. Eur. Supplement 9.7, effective April 2019. Use the applicable current chapter and method for the actual instrument mode; do not apply the Ph. Eur. table automatically to other compendia or methods. EDQM, revised Ph. Eur. 2.2.24 notice; EDQM 2019 chapter presentation.

Responsibilities

• Analyst or designee: Confirm the instrument is available and within its approved status, follow the applicable method and controlled procedure, and record the work and any abnormal event.
• QC instrument or process owner: Maintain the approved procedure, calibration programme, current accessory and software configuration, and instrument records.
• Quality unit: Review and approve the site procedure and its acceptance criteria.

Role names, training audience, distribution and the calibration form are defined in the site’s document-control system.

Procedure

Pre-use checks

1. Confirm the instrument identification, calibration status and any restrictions on use. Do not use an instrument that is overdue or outside its approved specifications.
2. Confirm that the selected accessory, measurement mode, sample preparation and method settings match the approved product method.
3. Sign in using the site’s approved access controls. Do not share account credentials.
4. Record the method, product and batch or sample identifiers, instrument and accessory, date, analyst and software record location.

For U.S.-regulated operations, 21 CFR 211.160(b)(4) requires a written calibration programme with suitable intervals, directions, schedules, accuracy and precision limits, and action for results outside those limits; instruments outside established specifications must not be used. This requirement does not set a universal quarterly interval. 21 CFR 211.160(b)(4), current eCFR.

Measurement

1. Power on and initialise the instrument according to its current manufacturer instructions. Wait for any required self-test or system-suitability check to complete.
2. Select the approved measurement mode and accessory. Use settings, resolution and sample-preparation steps from the method and instrument procedure.
3. Acquire a background using the same configured conditions required by the method.
4. Prepare and load the sample as specified by the approved procedure. For ATR, make suitable contact with the crystal without exceeding the manufacturer’s recommended pressure. For transmission measurements, use the specified cell or sample presentation.
5. Acquire the spectrum and review the result against the applicable specification or reference spectrum.
6. Preserve the original spectrum, metadata and processing history. Do not smooth, normalize, correct, convert or peak-pick data for a quantitative result unless the method and validated system procedure permit it and preserve the original data.
7. Record the conclusion, any processing performed, reviewer and any deviation. A printout may support review but must not replace the complete electronic or original record where that record is required.

For FDA-regulated operations, 21 CFR 211.194(a) requires laboratory records to include complete test data with enough identification to connect the data to the sample and lot, the method, the results, the person performing the test and the review. 21 CFR 211.194(a), current eCFR. FDA’s Data Integrity and Compliance With Drug CGMP: Questions and Answers (December 2018) discusses reliable and accurate data and risk-based controls; it is nonbinding guidance. Official FDA guidance.

Wavenumber-scale verification

When the Ph. Eur. method applies, use the value for the instrument’s measurement mode. The EDQM’s 2019 public presentation for the revised Ph. Eur. 2.2.24 lists four transmission positions and different ATR positions; each has a ±1.0 cm⁻¹ tolerance.

For another compendium (for example USP <854>) or a product-specific method, use its current requirements. The older seven-position list (3060.0, 2849.5, 1942.9, 1601.2, 1583.0, 1154.5 and 1028.3 cm⁻¹) is not the current Ph. Eur. 2.2.24 table and is not used here.

Resolution and calibration frequency

Example in-house criterion (not a pharmacopoeial requirement): This example SOP uses quarterly checks. Resolution and other FTIR performance criteria (reference film, mode and limits) must come from the applicable current compendial chapter (Ph. Eur. 2.2.24 or USP <854>), the approved method and the site’s calibration programme; two absorbance-difference limits are not given here because the compendium, mode and film were not identified.

Set the interval, reference material, measurement mode and acceptance criteria in the approved instrument calibration programme. Record individual results, the reference film identification, instrument and accessory, date, analyst, reviewer and disposition. Under 21 CFR 211.160(b)(4), when applicable, instruments that fail established specifications must not be used.

Example in-house criterion (not a pharmacopoeial requirement): Record all checks on the site’s approved calibration form, affix a calibration-status label when checks pass and label the instrument as under maintenance when a criterion fails.

Maintenance and cleaning

• Clean external surfaces and the sample area according to the approved instrument-specific procedure.
• Protect the optical surfaces and ATR crystal from scratches, incompatible solvents and residue.
• If liquid or solvent enters the instrument, stop use and contact the approved service route rather than attempting an unapproved repair.
• Record cleaning, maintenance, service, calibration and return-to-use activity in the approved instrument log.

Example in-house criterion (not a pharmacopoeial requirement): Follow the manufacturer’s manual for approved cleaning agents, method and optical components that must not be wiped, and the site’s service escalation route. Example: use a dry, soft cloth, avoid solvents on the instrument body, and contact the manufacturer’s service if solvent enters the instrument.

Example in-house criterion (not a pharmacopoeial requirement): Accessory and window materials (for example ATR crystal type, cell windows), permitted sample types, solvents and cell compatibility depend on the installed instrument and the product method. Follow the manufacturer’s manual and the approved method; some cell windows are damaged by water, so check compatibility before use.

Example in-house criterion (not a pharmacopoeial requirement): This example says to use a helium-neon lamp to keep the sample-preparation area dry and to purge only with clean, dry, oil-free nitrogen, avoiding flammable gases.

Records and retention

Maintain the calibration and performance-check results, status decisions, raw spectra, metadata, processing records, sample and method identifiers, cleaning and maintenance entries, service reports, deviations, training and review records.

Retain batch-associated GMP records for at least 1 year after the expiry date of the respective product batch. Where EU GMP applies, EudraLex Volume 4, Part I, Chapter 4, §4.11 requires batch documentation to be retained at least 5 years after QP certification if that is longer. Follow longer periods required by local law, the marketing authorisation or the approved site schedule. See EudraLex Volume 4, Part I, Chapter 4, Revision 1 (effective 30 June 2011), §4.11 and 21 CFR 211.180(a), current eCFR.

Training

Train analysts and reviewers on the approved procedure, sample-preparation and accessory use, data-system records, calibration and actions for an out-of-specification result.

Distribution and annexure

Maintain controlled distribution through the site’s document-control system. This example identifies Annexure I as a calibration data sheet; retain it only if the current approved form exists.

Abbreviations

• ATR: Attenuated total reflectance
• FTIR: Fourier-transform infrared spectroscopy
• QC: Quality control
• SOP: Standard operating procedure

See also: Operation and calibration of a UV-visible spectrophotometer, maintenance of laboratory instruments, and management of reference standards and solutions.

References

• European Directorate for the Quality of Medicines & HealthCare, Ph. Eur. General Chapter 2.2.24, “Absorption spectrophotometry, infrared,” revision in Supplement 9.7 (effective April 2019): official revision notice and EDQM 2019 presentation.
• United States, 21 CFR 211.160(b)(4), “General requirements,” eCFR version up to date as of 14 October 2026: official regulation.
• United States, 21 CFR 211.194(a), “Laboratory records,” eCFR version up to date as of 14 October 2026: official regulation.
• United States, 21 CFR 211.180(a), “General requirements,” eCFR version up to date as of 14 October 2026: official regulation.
• U.S. Food and Drug Administration, Data Integrity and Compliance With Drug CGMP: Questions and Answers, Guidance for Industry (December 2018), nonbinding: official guidance page.
• European Commission, EudraLex Volume 4, Part I, Chapter 4, “Documentation,” Revision 1 (effective 30 June 2011), §4.11: official PDF.

Revision history