SOP for Good Laboratory Practices (GLP), What are Good Laboratory Practices (GLP), Good laboratory practices (GLP) as per guideline (USFDA) ,Good Laboratory practices (GLP) examples and principles, Schedule L1 requirements

SOP for Good Laboratory Practices (GLP), What are Good Laboratory Practices (GLP), Good laboratory practices (GLP) as per guideline (USFDA), Good Laboratory practices (GLP) examples and principles, Schedule L1 requirements

This SOP is introducing what practices need to be performed in the laboratory for consistent, reliable analytical results, Good Laboratory Practices (GLP) guidelines (USFDA), Examples of Good laboratory Practices (GLP), GLP principles, Rounding rules, Schedule L1 requirements.

SOP for Good Laboratory Practices (GLP), What is GLP, GLP as per guidelines GLP examples and principles, Schedule L1 requirements


1.0 PURPOSE:

The purpose of this SOP (Standard Operating Procedure) is to provide the guideline for Good Laboratory Practices for the Quality Control laboratory.

2.0 SCOPE:

This procedure is applicable for Good Laboratory Practices at Quality Control Department i.e. Stability, Chemical (Wet) Laboratory, Instrumentation Laboratory, microbiology, Analytical Development, etc.

3.0 RESPONSIBILITY:

3.1 Quality Control

3.1.1 All employee working in the quality control follows the Good Documentation Practices (GDP)ALCOA+, Good Laboratory Practices.

3.1.2 Prepare and review the specification, Standard test procedure (STP), test protocols, SOP, and standard formats.

3.1.3 Record and report the analytical results.

3.1.4 Maintain the laboratory as per the regulatory requirement.

3.2 Quality Assurance

3.2.1 Approve the specification, Standard test procedure (STP), test protocols, SOP, and standard formats.

3.2.2 Verify for the laboratory as per the regulatory requirement.

4.0 DEFINITIONS

4.1 Good Laboratory Practices (GLP)

Practices follow during analysis and clinical work for the reliable, accurate, consistent, reproducible analytical and research-oriented results to maintain the integrity of the product.

4.2 Chemical (wet) Laboratory

Laboratory in which chemical, reagents, diluents, indicators, etc. kept and chemical analysis perform i.e. volumetric analysis, pH testing, degradation test, etc. and preparation of the reagents, indicators, etc. Chemical laboratory equipped with a water bath, glassware’s, fume chamber, weighing balances etc.

4.3 Instrumentation laboratory

Laboratory in which testing perform using the instruments i.e. HPLC, GC, Karl Fischer analyzer, particle size analyzer, etc.

4.4 Standard Operating Procedure:

The written procedure, instruction available for consistency, uniformity in the process, practices at the workplace. Refer to SOP for more details.

4.5 Specification

The specification is a list of tests, general information about the drug substance or drug product references to test method, and suitable acceptance criteria which are specific numerical limits, ranges, or other criteria for the tests described. It is a set of criteria for the confirmation of the drug substance or drug product for its intended use.

4.6 Standard Test Procedure (STP) / Method of Analysis (MOA)

Standard Test Procedure is a detailed method for drug substance or product analysis. It covers the test method, set acceptance criteria, the way of analysis, what are the parameters, which instrument and equipment required to perform the test procedure. It covers both qualitative and qualitative tests.

4.7 Test Protocols

Test protocols are data recording sheets with details analytical test methods. It covers both qualitative and qualitative tests with statistical analytical reports. It includes all the details of the Standard Test Procedure with data recording space. Data recorded in test protocols should electronically or manually (handwritten).

Test protocols are used for the reporting of the test includes the statistical report of the test, weight print of balance, all the manual calculations, etc.

4.8 Sample:

A small amount of material, product collected for testing, verification, or checking purposes from the bulk material /product.

4.9 Buffer Solutions / pH Calibration Solutions:

Buffer solutions resist changes in the activity of an ion on the addition of substances that are expected to change the activity of that ion. Buffer used to resist change in pH so, preparation remains in stable condition. They are chemical solutions used for the calibration.

4.10 Indicator

Indicators are reagents used to determine the specified endpoint in a chemical reaction, to measure the hydrogen-ion concentration (pH), or to indicate that the desired change in pH has been affected.

5.0 PROCEDURE

5.1 Standard Operating Procedure (SOP), Standard Formats (SF), Specification, Standard Test Procedure (STP) and test protocols.

5.1.1 QC department should review SOP, Specification, Method of analysis, Standard formats prior to implementation and approved by Head QA.

5.1.2 All persons working in the laboratory should be work according to the approved SOP, Specification, Method of analysis, Standard formats, test protocols.

5.1.3 Review and revise all the SOP, Specification, Method of analysis, Standard formats periodically to ensure suitability and regulatory compliance.

5.1.4 A trained and qualified personnel should perform the relevant analysis. Analyst qualification should be necessary for all personnel prior to appointing for the work in the laboratory.

5.1.5 Analysis should be performed as per the approved specification and method of analysis and result recorded in the standard test protocol/formats.

5.2 Chemical (Wet) Analysis Laboratory

5.2.1 All glassware should be clean before analysis.

5.2.2 Before using a burette and pipette rinses it with a solution that is using for the analysis.

5.2.3 Ensure that the temperature during dilution, at the time of volumetric measurement and standardization, is maintained i.e. at about 25°C or specified.

5.2.4 Store the light-sensitive solution in the amber-colored containers only.

5.2.5 If accurate dilutions are required, then use clean Class A grade volumetric glassware.

5.2.6 Storage period of the chemicals as per below:

5.2.6.1 Solid chemicals/reagents - 2 years after opening the container.

5.2.6.2 Liquid Chemicals/reagents/Buffer - 1 years after opening the container.

5.2.6.3 Hygroscopic material - 6 months after opening the container.

5.2.7 In case the manufacturer’s expiry is less than the above-defined date, then consider manufacturer’s expiry date.

5.2.8 Samples should collect as per procedure and not contaminate during collection and storage period.

E.g. New bottle of Hydrochloric acid is open on date 27/10/20, its expiry date is 26/10/21. But the manufacturer’s expiry date is 31/12/20 then considers the manufacturer’s expiry date i.e. 31/12/20.

5.2.9 Water for injection (WFI) should be changed once in 24 hrs with label contains time, sign, and date.

5.2.10 Use hand gloves, mask, goggle while handling concentrated acid/ base / hazardous chemicals.

5.2.11 Degassed HPLC solvents and mobile phase before use.

5.2.12 Toxic and flammable chemicals always store in a separate area under lock and key.

5.2.13 Place all the clean and unbroken glassware in the sample tray and properly label it before solution preparation to avoid cross-contamination of the glassware or sample solution

5.2.14 Achieve room temperature (RT) of reference standard / working standard prior use.
5.2.15 Issued working standards are kept in the desiccator and sealed the bottle immediately after use. Maintain the working standards usage log.

5.2.16 Unspecified temperature sensitive material keeps in the refrigerator.

5.2.17 If any material heated or chilled then allowed to reach room temperature prior to weighing, pipetting or measuring.

5.2.18 Dried material should be kept in desiccators.

5.2.19 Verify the expiry date of the material prior to use and expired reagents and chemicals not to be used for testing.

5.2.20 Always follow Material safety data sheet (MSDS) to discard the material.

5.2.21 Consideration of the meniscus during performing titration:

5.2.21.1 For colorless solutions in the burette - lower meniscus

5.2.21.2 For colored solutions - upper meniscus

5.2.22 At the time of analysis where the print out of reading is not possible then verify results by authorized person and make signs. e.g. Assay by manual titration, pH meter the result, Conductivity meter, etc.

5.2.23 Always follow the safety procedure to avoid accidental spillage of acids and corrosive agents.

5.2.24 Use fume chamber for highly acidic, basic, reactive material, a hazardous material.

5.2.25 For small containers like HPLC vials, GC vial, sample tubes, 5 ml volumetric flasks etc. difficult to the affixed status label on the container, in such cases use a permanent marker to provide the identity of the container.

5.2.26 If the solution to be kept for more than one hour, only in that case affix the status label otherwise use permanent marker for identification purposes.

5.2.27 Adjust the zero before starting titration in the burette reading.

5.2.28 Tied reagent bottle caps/stopper/lead with thread, with respective bottleneck to avoid mix up and contamination.

5.2.29 Reagent preparation / volumetric solution method should be reviewed after every two years or whenever change in respective Pharmacopoeial method.

5.2.30 For the preparation of the mobile phase measure pH in aqueous media before mixing with solvents.

5.2.31 Use mobile phase within 48 hrs after preparation or as per mobile phase

stability data or protocol-based study for mobile phase validity.

5.2.32 All sample prepared for assays such as HPLC, GC runs should be tested within 24 hours of preparation unless defined in the analytical procedure. If the 24 hours are exceeded the vials must be discarded and prepared new.

5.2.33 Record mobile phase preparation date and weight of chemical, for preparation of mobile phase and making pH adjustment.

5.2.34 Never leave any chemical reaction-taking place on the gas i.e. boiling, distillation, refluxing unattended.

5.2.35 Always clean spatula prior to collect the solid reagent from the container.

5.2.36 Never return unused reagent to the reagent container. There is chance of contamination and its directly impact on cost, time, and results.

5.2.37 Always use beaker during pH adjustment never try narrow neck container.

5.2.38 Water for Injection (WFI) or Milli-Q water is used for the mobile phase preparation.

5.2.39 Use glass syringe/ syringe without rubber bung for sample dispensing.

5.2.40 Do not use chemical without a label, unable to read the label, damaged container, expired, or physical the property changes of the material.

5.3   Data Recording

5.3.1 Specification and Standard Test Procedure (STP)Standard operating procedures

5.3.2 Test reports, test protocols, and records these all document should be under the control of QC.

5.3.3 QC should maintain, verified and secure the operation, calibration, and maintenance record of instrument.

5.3.4 All documents should be approved by an authorized person with a sign and date.

5.3.5 All recorded data and documents should be verified and reviewed by authorized persons.

5.3.6 Always perform the analysis as per the updated version of the specification, STP, and test protocols.

5.3.7 Follow the ALCOA+ rule (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, Available) during the recording of the data.

5.3.8 Retest sample should be available in suitable conditions during retesting.

5.3.9 Do not overwrite the entry in the document. Follow the Good Documentation Practices (GDP). Strick a single horizontal line on the wrong entry with a pen and then write the corrected entry with sign and date.

5.3.10 Make all recordable entry in the respective logbook with a start time of analysis and at end time of analysis.

5.4 Instrumental Analysis laboratory

5.4.1 Always use the calibrated Instruments and measuring devices before starting the analysis. Verify the calibration status to the updated status of Instruments and measuring devices. Do not use a non-calibrated Instrument/ measuring device.

5.4.2 Calibrate all the instruments as per the available procedure.

5.4.3 The instrument shall be tagged with the tags showing the instrument detail and indicating its calibration status.

5.4.4 Unique identification number should be created for each instruments, columns, and equipment.

5.4.5 Due date of instrument calibration should be mentioned in testing protocols for tracking and trustworthy data.

5.4.6 Logbook should be available for each Instrument/equipment

5.4.7 Daily usage of each Instrument/equipment should be recorded in the logbook with start time and end time.

5.4.8 Never use damage instrument/equipment and if any abnormality found during analysis then never proceed with the procedure.

5.4.9 Electrode of pH meter or conductivity meter should be clean with purified/Milli Q/WFI/DRO water, wipe off with the help of a tissue paper gently and never rub the electrode during wiping.

5.4.10 Never use rough surface paper for wiping the electrodes.

5.4.11 Always keep pH electrodes dipped constantly in the KCl/7 pH Buffer and conductivity electrodes dipped in purified water.

5.4.12 Do not delete or manipulate any electronic record or manual record.

5.4.13 After completion of HPLC analysis remove the column from the system and seal both ends with the cap.

5.4.14 Column of HPLC and GC handles with care.

5.4.15 Do not flush the reverse-phase column with 100% water or 100% organic solvent. Store reversed-phase columns in at least 50% organic solvent. Never store a column with a buffer.

5.4.16 Always use fresh HPLC vials for analysis.

5.4.17 If any system suitability parameter of HPLC or GC not achieved, and cause identified as poor efficiency of the column then destroy column by de-shaping. Record the details of destruction in format.

5.5 Dilutions

5.5.1 Use Class A volumetric glassware for the dilution until the analytical procedure not stated the specific requirement.

5.5.2 Autopipettes stated in the individual specification are meet the requirements of Class-A volumetric glassware.

5.5.3 Qualified autopipettes only used for the analysis.

5.5.4 Volumetric glass pipettes are used for measuring the analytical solvent, reagent. a solution like 1 ml, 5 ml, 10 ml, etc.

5.5.5 If a specification requires measuring 10 mL but no special requirement for use of a volumetric pipette, then graduated or measuring cylinder can be used for the measurement.

5.5.6 Unless otherwise stated by the individual specification, autopipettes or dispensers are not to be used for the addition of samples.

5.5.7 If collecting solvent/chemical/reagent from the original/source container for preparation of standard/sample solutions, then some amount of solvent/chemical/reagent will be transferred to a clean beaker before pipetting. After pipetting discard the remaining amount of solution.

5.5.8 If there is no specified a requirement of the temperature for the dilution then dilution should be performed at 25°C.

5.6   Storage of Reagents, Standards, and Test Solutions

5.6.1 Follow the MSDS (Material Safety datasheet), manufacturer/supplier instruction, associated Pharmacopeia, or applicable analytical procedure for storage condition of the respective chemical/reagent etc.

5.6.2 Keep the reference standard/working standard vial in the refrigerator.

5.6.3 If reagents & solution required any special storage the condition then fulfill the same storage condition.

5.6.4 Hygroscopic material (moisture absorbing) should be kept in a desiccator. Desiccants (Silica gel) should be replaced when the color starts to change.

5.6.5 Reference standard and the working standard never mix/keep with chemical/reagent/solution.

5.7 Allocation of Expiry Date

5.7.1 Solid chemical, a liquid chemical with an expiry date refers to point no. 5.3.6.

5.7.2 For reagents, chemical received without an expiry date or solutions prepared in the lab without an expiry date. Determined per method validation.

5.7.3 Assign the following dates until specified by the manufacturer or specifically designed to establish the stability (expiry date) of the reagent.

5.7.3.1 Vendor Chemicals or reagent (Solids, liquids/solvents) - One-year after opening date and not exceeding the manufacturer’s expiry date. E.g. ethers and peroxides.

5.7.3.2 Buffer Solutions / pH Calibration Solutions - 3 months from the date opened and not to exceed the manufacturer’s expiry date.

5.7.4 Indicators

5.7.4.1 Liquid Indicators: 1 year from date received or prepared

5.7.4.2 Solid Indicators: 2 years from the date received or prepared

5.8 Raw Material, Initial, In-process and Final Analysis

5.8.1 Separate sets of blank (only solvent), test solutions, reference/working standards, and standardized reagents should be prepared for the initial and the final analysis of samples.

5.8.2 The same analyst should not perform both the initial and the final analysis for a given component. In the case of an instrumental analysis where test results are documented via a printout, it is acceptable for the same analyst to perform both the initial and final component analysis.

5.9 Receiving of new Glassware’s

5.9.1 Check the glassware physically for any damage, breakage, volume prior to receiving consignment and enter the details in the glassware receiving register at the time of receiving new glassware.

5.9.2 Class ‘A’ glassware received along with its certificate for analytical (COA) testing.

5.10 Data Handling

5.10.1 If linear regression analysis is used for assay calculation, then the assay should be validated, and the correlation coefficient requirement should be pre-established. The correlation coefficient (r) should be 0.99 or greater until not specified in the test method.

5.10.2 When calculations are performed by an un-validated computer software the calculations should be manually verified.

5.11 Review of Chromatograms

5.11.1 Review the chromatograms for data integrity requirements, all set parameters, and system suitability.

5.11.2 Ensure a steady baseline

5.11.2.1 Ensure a steady baseline by viewing chromatogram for the entire run time.

5.11.2.2 A steady baseline for an isocratic or isothermal run is a flat line, and absent of unusual noise, beginning at relatively zero response.

5.11.2.3 A steady baseline for a gradient run includes sloping lines as well as relatively flat lines that correspond to the gradient ramps.

5.11.2.4 A similar profile is observed for temperature programming where the baseline slopes as the temperature increases/decreases and remains relatively flat at a constant temperature. For example, chromatogram, refer to the standard chromatogram in the analytical procedure.

5.11.3 Ensure correct elution order

5.11.3.1 The elution order in the standard and sample chromatograms should be consistent.

5.11.4 Integration of Peaks

5.11.4.1 Refer to the test method, standard procedures, software guide help for specifics with integration parameters.

5.11.4.2 Only peaks for reported analytes need to be integrated until instructed by the analytical procedure for the assay or protocol.

5.11.4.3 Ensure consistency with integration.

5.11.4.4 The integration parameters programmed into the validated software should be the same for all chromatograms in the sequence.

5.11.4.5 Start with automatic integration to correctly integrate all or most of the peaks.

5.11.4.6 Ensure consistency with integration based on visual examination of the chromatograms. E,g.  baseline-to-baseline peak integration, review peak for tailing peaks, etc.

5.11.4.7 Integrate all standards and samples in the same manner.

5.11.4.8 In some cases, manual integration of individual chromatograms may be needed to ensure the correct integration of a peak. For example, cases, where a peak is eluting on the shoulder of the peak of the testing sample, need to be manual integration.

5.11.4.9 In case of Related substances and residual solvents test, different processing method can be used for integration of sample solution providing justification for using a separate method and signed by Supervisor/Designee.

5.11.4.10 Any manual integration performed must be reviewed during audit trail review by the supervisor/Head of QC/Quality Assurance to ensure that the integrity of the data is maintained.

5.11.4.11 In case of an assay, Samples, and standards should be integrated in the same manner.

5.11.4.12 Multiple injections from the same vial or injections from multiple vials of the same solution should produce chromatograms with similar profiles, and similar responses for the targeted analyte.

5.11.4.13 Software processing methods maybe created to optimize integration parameters and provide consistency.

5.11.4.14 In case of reporting of system suitability parameter for the calculation considered the worst-case scenario of replicate injections.

Example: -

 

Injections

 

Parameter

Asymmetry

Theoretical Plates

Tailing Factor

1

Standard - 1

5420

1.12

2

Standard -2

5320

1.17

3

Standard -3

5489

1.16

4

Standard -4

5502

1.19

5

Standard -5

5431

1.16

6

Standard -6

5399

1.13

 

In the above case consider the tailing factor for the calculation to be reported as 1.17 and theoretical plates to be reported as 5320.


5.12 Equipment

5.12.1 Use calibrated, validated, or qualified equipment for the testing.

5.12.2 A procedure should be available for equipment calibration, validation/qualification, Operation, maintenance of lab equipment.

5.12.3 If the equipment is controlled by software, then the software should be validated. Computer systems used in the laboratory must have security requirements detailed by a procedure.

5.12.4 Audit trial is required for all the required instruments.

5.12.5 Daily verification of balance required once a day prior to use.

5.12.6 If cleaning of glassware is manual, then the cleaning procedure should be validated.

5.12.7 If automated glassware cleaning equipment using for the cleaning of glassware, then equipment and procedure should be validated.

5.13 Follow procedure after Printer Failure

5.13.1 If instrument attached with printer and printer is not working or any failure to print the data, then generate a work order and submit it to the lab maintenance/maintenance department.

5.13.2 If not repaired immediately, connect other printers (working Condition) from other areas with help of an IT person and start the process

5.13.3 If the printer fails during weighing the material, repeat step No. 5.14.1 and do not consider the taken weight for analysis purposes. If the issue not cleared, then perform weighing on another weight balance.

5.14 Rounding rule for analytical result obtained after testing

5.14.1 This procedure is applicable for rounding off the calculated/obtained result of the test parameter result.

5.14.2 Rounding rule should be applicable after getting a final digit (last digit).

5.14.3 Slope for linearity should be rounded for reporting purposes but the original value should be as it is and used for any additional required calculations.

5.14.4 If acceptance criteria are fixed value then rounding rule is not applicable.

5.14.5 Rounding rule starts from the last digit after the decimal place from the right-hand side.

5.14.6 If this digit is smaller than 5, it is eliminated, and do not increase the next number.

5.14.7 If this digit is equal to or greater than 5, it is eliminated, and the preceding digit is increased by 1.

E.g. for better understanding. How deals with analytical results.


Acceptance criteria

Result obtained

Rounded / Reporting Result

Pass / Fail

Test Conform

Assay limit more than 99.0%

98.96%

99.0%

Pass

Yes

98.92%

98.9%

Fail

No

98.95%

99.0%

Pass

Yes

 

Assay limit less than 102.5%

102.55%

102.6%

Fail

No

102.46%

102.5%

Pass

Yes

102.45%

102.5%

Pass

Yes

Assay 98.0% to 102.0%

 

97.95%

98.0%

Pass

Yes

97.94%

97.9%

Fail

No

102.95%

103.0%

Fail

No

Limit test / Impurity test less than 0.03%

0.035%

0.04%

Fail

No

0.025%

0.03%

Pass

Yes

0.037%

0.04%

Fail

No

Limit test less than 0.3%

0.34%

0.3%

Pass

Yes

0.35%

0.4%

Fail

No

 

Limit test 5 ppm

3.5 ppm

4 ppm

Fail

No

5.4 ppm

5 ppm

Pass

Yes

4.5 ppm

5 ppm

Pass

Yes

Tailing Factor (limit NMT 1.5%)

1.55 %

1.6%

Fail

No

1.54%

1.5%

Pass

Yes

% difference (limit NMT 1%)

1.4%

1%

Pass

Yes

1.5%

2%

Fail

No

Signal to noise ratio (limit NMT 5%)

5.5%

6%

Fail

No

5.4%

5%

Pass

Yes

5.14.8 Rounding should be applicable for the final result only, not on the intermediate results.

5.14.9 Negative values as a result of a calculation are possible.  Unless otherwise stated in the test specification, negative results will be reported as ‘0’ (zero).

5.14.10 When adding, subtracting, multiplying or dividing numbers, final results should be rounded till final reporting digits.

Examples:

Details

Addition

Subtraction

Multiply

Divide

Value-1

7.4

7.4

7.4

7.4

Value-2

+1.52

-1.52

*1.52

/1.52

Value-3

+ 0.1675

- 0.1675

*0.1675

/0.1675

Final results

= 9.0875

= 5.7125

=1.88404

=29.0652

double digit reporting after decimal

9.09

5.71

1.88

29.07

Single-digit reporting after decimal

9.1

5.7

1.9

29.0

5.14.12 Electronically generated results value reported as it is e.g. weight of material on balance.

5.14.13 Manufacturer/supplier result on COA should not consider as our reporting result, perform in-house testing and the obtained result consider as our final results.

6.0 ABBREVIATION

HPLC – High-Performance Liquid Chromatography

GC – Gas Chromatography

COA – Certificate of Analysis

QA – Quality Assurance

QC- Quality Control

SOP – Standard Operating Procedure

DRO – Double Reverse Osmosis

KCl – Potassium Chloride

NMT – Not more than

7.0 REFERENCES

7.1 21 CFR part 211 subpart I - Laboratory Control

7.2 Schedule L1 

7.3 Handbook of Good Laboratory Practices.

7.4 United State Pharmacopeia (USP)

8.0 HISTORY       

Not Applicable

9.0 ANNEXURES          

Not Applicable


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