Checklist for Review of Analytical Raw Data (Chemical)

Checklist for review of analytical raw data generated during the chemical analysis of finished drug product, the raw material (API-Active Pharmaceutical Ingredient / Excipient), Inprocess samples and stability study sample analysis.

Checklist for Review of Analytical Raw Data (Test wise)

1.0      Product Information (Review of Raw Data / Report) :

    • Name of material (Brand name, Generic name)Raw Data Review Checklist
    • Pharmacopoeial status if any.
    • Manufacturer supplier name.
    • Batch No.,
    • A.R. No.,
    • Batch size.
    • Mfg. Date,
    • Exp. Date.

2.0      General Check Points (Review of Raw Data / Report):

    • Analytical method, effective date, revision number.
    • Calibration status of Instrument.
    • Instrument code No.
    • Instrument usage log entry.
    • HPLC/ UPLC / GC/ IC column usage log entry.
    • Name and grade of reagents used in the analysis.
    • Code no. of buffer, reagents, volumetric, indicator.
    • Solution code no.
    • WS/RS/Impurity name.
    • WS/RS/Impurity code No./Lot No.
    • The potency of WS/RS/Impurity.
    • WS/RS/Impurity validity date.
    • Balance ID used in the analysis.
    • Standard and sample weight.
    • Standard and test preparation.
    • Dilution, sonication time,filter, centrifuge of sample as per ATP .
    • Weight slip print out and any other print out with B.No. /A.R. No. and signature of the analyst.
    •  Any stamp on the chromatogram, UV spectra, histogram, etc.
    • Date of analysis.
    • Countersignature where ever applicable.
    • Conversion factor, calculation as per ATP and results meeting the specification.
    • Reason for cancellation of chromatogram / UV spectra/ histogram or other print out of respective instrument and authorization.
    • Signature of the analyst on raw data, chromatogram, UV spectra, histogram or any other printout.
    • Signature of authorized by / approved by wherever applicable.
    • Any deviation from procedures defines in ATP.
    • Any deviation from SOP flow.
    • Event/ incident/ OOS/OOC/OOT/ repeat analysis handle as per respective SOP.
    • Activity is performed in chronological order of date.
    • Any replacement of page in template /worksheet/ chromatogram/ UV spectra/ or any other document.

3.0     Test – Identification (Review of Raw Data / Report)

    • Identification by IR :

    • Purity index (should be greater than 0.95), wherever applicable.
    • A comparison of the sample spectrum with the WS spectrum should be concordant.
    • Container no. Vs. IR spectrum.
    • Spectrum range.
    • Note: Analyst/reviewer shall verify and ensure the electronic data as listed above in the system is as per the test procedure.
    • Identification by Color Development :

    • Observation as per ATP and countersignature by a person who checked in to the lab.
    • Identification by melting point :

    • Dried material use.
    • Observation and countersignature by the person who checked in to the lab.
    • Identification and related substance by TLC :

    • Mobile phase preparation.
    • TLC plate and TLC tank no.( if applicable).
    • Procedure for the saturated tank, impurity solution preparation in case of related substance.
    • The mobile phase run on the plate.
    • Application, detection, or spray solution preparation or code no.
    • The intensity of the spots, size of the spot whichever applicable, check for the countersignature of the person who observed the TLC plate along with analyst.
    • UV lamp intensity for observation of spot as per ATP.
    • Trace paper sketch or Xerox copy of the TLC plate.

4.0     Analysis by UV spectrophotometer (Review of Raw Data / Report)

    • Blank absorbance.
    • UV spectrum by peak and valley detection.
    • Wavelength (maxima) used in the analysis.
    • Absorbance at particular maxima, compare sample spectrum with WS. Spectrum. -variation of wavelength should be verified as per the respective method.
    • Sample preparation.

5.0      Specific optical rotation

    • Length of tube used in the analysis.
    • The temperature during sample reading.
    • Sample preparation and diluent used for sample preparation.
    • Sample preparation time and measurements time.
    • Blank and sample reading as per ATP and calculation (wherever applicable).

6.0      Assay and related substances by HPLC

    • Mobile phase preparation, gradient program(if applicable )
    • pH adjustment, filter, degas, sonication and stirring of mobile phase (as per STP).
    • System suitability solution preparation (resolution solution preparation).
    • Column no., column dimension, 
    • The wavelength, column oven temperature, sample cooler temperature,
    • Peak integration and integration type, manual integration, chromatogram no.,
    • No. of injection (as per STP), injection volume, integration parameter,
    • System suitability, RSD, theoretical plates, tailing factor, resolution,
    • Proper peak identification, peak merging with known impurity or active compound,
    • Increase or decrease of placebo/ blank peak response in sample chromatogram.
    • Sequence print, method print, processing method print, peak shape, run time, retention time.
    • Peak identification due to extraneous peak, placebo peaks or peak found from the mobile phase and diluent.
    • Any peak at the retention time of active ingredient in the mobile phase, diluent, and placebo.
    • Increases or decreases in area response of one or more of the samples when compared with standard or sample area.
    • Baseline/ retention time /peak height or peak area shift throughout the run.
    • Chromatographic pattern or gradient pattern throughout the run.
    • The decrease in plate count, increase in tailing and fronting during run, integration inhibition.
    • The peak should be 70 % of the full-scaled chromatogram (for assay) auto scaled (if required ) (and for related substance peak shape and peak integration shall be clearly visible.
    • Peak purity, peak threshold, purity angle (if required).
    • Note: Analyst/reviewer shall verify and ensure the electronic data as listed above in the system as per the test procedure.

7.0       Assay, Related substances and residual solvent by GC

    • The carrier gas, column program, injector temperature, detector temperature, split ratio, type of detector.
    • Headspace condition (if applicable) as per the method.
    • System suitability solution preparation (Resolution solution preparation).
    • Column number, column dimension, injection volume, temperature,
    • Integration parameter, system suitability, RSD, theoretical plate, tailing factor, resolution, proper peak identification,
    • Peak merging with known impurity or active compound, increase or decrease of placebo/ blank peak response in the sample.
    • Chromatogram, manual integration, chromatogram No., No. of injection (as per STP).
    • Sequence print, method print, processing method print, peak shape, run time, retention time.
    • Peak integration, extraneous peak, placebo peaks or peak found from the diluent and peak should be 70 % of the scale.
    • Any peak at the retention time of active in diluent and placebo.
    • Increases or decreases area response of one or more of the sample when compared with standard or sample area.
    • Baseline/ retention time /peak height or peak area shift throughout the run.
    • Chromatographic pattern or gradient pattern throughout the run.
    • The decrease in plate count, increase in tailing and fronting during run, integration inhibition.
    • Note: Analyst/reviewer shall verify and ensure the electronic data as listed above in the system as per the test procedure.

8.0      Test – Content uniformity by HPLC

    • Same as assay and related substances by HPLC.
    • The reviewer shall verify all the area/ absorbance filled in template/worksheet/ hard book is correct.
    • Minimum and maximum results value.
    • Acceptance value.
    • The reviewer shall check only minimum and maximum. Calculation during raw data review.

9.0      Test – Assay by titration (Review of Raw Data / Report)

    • Strength of volumetric solution.
    • Assay on as-is basis, dried basis or anhydrous basis.
    • Validity date of volumetric solution.
    • Printouts and signature of the analyst.
    • Method parameter used for titration.
    • Water content/LOD used in the calculation.
    • The equivalent factor used in the calculation.
    • Electrodes used in the titration.
    • Results and calculation (where ever required).

10.0    Test – Sulphated ash or loss on ignition/residue on ignition

    • Drying procedure of crucible.
    • Addition of H2SO4 or HNO3, temperature, two constant weights after ignition.
    • Cooling procedure after ignition.
    • Results and calculation.

11.0    Test – Loss on drying

    • Sample weight, temperature and time of drying sample.
    • Two constant weights (if required) and calculation.

12.0    Test – Limit test/appearance of solution /acidity and alkalinity

    • Observation, the countersignature of another person who has checked the sample in the lab.
    • pH (where ever applicable).
    • Verification of pH meter standardization.
    • Temperature (where ever applicable).

13.0    Test – Extractable volume and volume variation :

    • Rinsing of the syringe or measuring cylinder and its capacity.
    • Volume check.
    • Specified no. of container and minimum, maximum and mean result.

14.0    Test – Moisture content/water determination by Karl Fischer reagent :

    • Factor determination.
    • Sample weight.
    • Drift during the analysis.
    • Printouts and signature of the analyst.
    • Method parameter used for water analysis.
    • The electrode used for analysis.
    • KF reagents used for water determination.
    • Results and calculation (wherever required).
    • Note: Analyst/reviewer shall verify and ensure the electronic data as listed above in the system as per the test procedure.

15.0    Test – Weight variation :

    • Weight of 20 units and average weight.
    • The individual weight of 20 units.
    • Minimum and maximum variation from the average weight.

16.0    Test – Disintegration time :

    • The volume of media, temperature, preparation of media.
    • Disintegration time.

17.0    Test – Dissolution :

    • Media preparation, degassing of media.
    • The volume of media, apparatus, time, temperature, start time and end time, RPM.
    • Wobbling & centering check before starting the dissolution.
    • Weight of each tablets/ capsules/ granules.
    • Sample withdrawn.
    • The reviewer shall verify all the area/ absorbance filled in template/worksheet/ hard book is correct.
    • Minimum and maximum results value.
    • Mean result value.
    • The reviewer shall check the only min. and max. Calculation during raw data review.

18.0    Test – Viscosity :

    • Temperature,
    • RPM,
    • Spindle number.,
    • Factor,
    • Calculation.

Abbreviations used in the checklist for Review of Analytical Raw Data and Report:

    • ATP: Analytical Test Procedure.
    • AR No. : Analytical Report Number.
    • API: Active Pharmaceutical Ingredient.
    • BET: Bacterial Endotoxin Test.
    • CSE: Control Standard Endotoxin
    • COA: Certificate of Analysis.
    • Exp: Expiry.
    • GC: Gas Chromatography.
    • GMP: Good Manufacturing Practices.
    • HPLC: High-Pressure Liquid Chromatography.
    • IC: Ion Chromatography.
    • IR: Infra-Red.
    • LOD: Loss On Drying
    • Mfg: Manufacturing
    • NA: Not Applicable.
    • NIST: National Institute of Standards and Technology
    • OOS: Out of Specification.
    • OOT: Out of Trend.
    • OOC: Out of Calibration.
    • PQ: Performance Qualification
    • QA: Quality Assurance.
    • QC: Quality Control.
    • RS: Reference Standard.
    • RSD: Relative Standard Deviation.
    • RPM: Revolution Per Minute
    • SOP: Standard Operating Procedure.
    • TLC: Thin Layer Chromatography.
    • UPLC: Ultra Performance Liquid Chromatography.
    • UV: Ultra Violet.
    • WS: Working Standard

pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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