Month: March 2021

Preventive Maintenance of Vibro Sifter


  1. OBJECTIVE            
  1. To lay down a procedure for Preventive Maintenance of Vibro Sifter – 12”, 30”.
  • 2.0 RESPONSIBILITY  
  • Assistant – Engineering  – To follow the SOP
  • Executive – Engineering – To comply the SOP
  • 3.0 PROCEDURE                      
  • Monthly Maintenance
  • Check the hopper supporting compression springs for tension and balancing of the hopper.
  • Check the motor amps and working condition should be with in the limits.
  • Check the lead weights for proper vibrating, if required increase or decrease the vibration according to the working action.
  • Lubricate the motor bearings by using grease gun.
  • Check the hopper holding clamps and gaskets, if required replace the gasket.
  • Yearly Maintenance   
  • Check the motor bearings condition for abnormality, if required replace the bearings.
  • Check the motor winding resistance, load current and starter contactors condition, if required clean the contactors with CTC or replace the contactors.
  • Check the castor wheels for free movement, if required clean the bearings and apply the grease to the bearings.
  • Check the condition of the compression springs, if required replace the springs with new springs.
  • 4.0 ABBREVIATIONS    
  • CTC : CARBON TETRA CHLORIDE
  • 5.0 REFERENCES           

Nil.

  • 6.0 ANNEXURES
  • Annexure-1    Monthly preventive maintenance checklist.
  • Annexure-2   Yearly preventive maintenance checklist.

Sampling and Release of Semi finished Product


  • SAMPLING OF SEMIFINISHED PRODUCT
  • Samples collected during granulation or blending stage for solid oral dosage forms shall be considered as semi finished product samples.
  • As per BPRR at the end of the each activity, production executive shall issue “SAMPLE TEST REQUEST FORM” to IPQA personnel.
  • IPQA personnel shall sample and submit all samples to the QC department after completion of process as per  

the Batch Manufacturing record through sample test request form. Incase of  validation samples, submit the

          samples as per the validation Protocol through   “VALIDATION SAMPLE TEST REQUEST FORM’

  • During dry mixing, samples shall be collected as per the validation protocol for the respective products.
  • After completion of drying process, IPQA executive shall collect the sample for LOD / Water by KF / water activity tests from different locations by using cleaned sampling thief and transfer to double polyethene bag  after mixing.         

       Approximately 5 grams of pooled sample shall be taken for the test.

  • After lubrication wherever applicable, IPQA person shall collect approximately 35 grams of composite blend from different locations of the IPC container / laminated bag after unloading from octagonal blender in the LDPE bag.
  • Samples of blend uniformity (Wherever applicable) are sampled as per validation protocol / Batch Manufacturing record are sampled in vials with rubber stoppers.
  • Blend uniformity samples shall be drawn with the unit dose sampler as per SOP
  • All samples collected by IPQA executive shall be affixed with duly completed and Signed SAMPLE FOR TESTING  

         label before sending to QC for  testing. 

   REALESE OF SEMIFINISHED PRODUCT:

  • After testing of the semi finished samples, QC shall issue in process Certificate of analysis along with Approved   

         Label and raw data to Section in charge QC/Analytical Assurance.   

  • Section In charge QC / Analytical assurance personnel shall review the COA and the raw data. If found satisfactory, Approved Label along with the In-process COA shall be forwarded to IPQA
  • Raw data shall be submitted to the documentation cell for archiving.
  • IPQA personnel shall complete the review of the and In process COA and the BPRR shall be signed off to release the batch for further processing.

      Note: If semi finished product is not meeting as per the specification, the same shall be investigated as per SOP      

       [Investigation of Out of Specification Results (OOS)] and SOP (SOP for Failure Investigation)

       

Control, Storage, Retention, Retrieval, and Disposal of Document(s).


Document shall be stored under lock and key in documentation room for the corresponding periods defined below (but not limited To):

LIST OF QUALITY RECORDS WITH RETENTION PERIODS

S.No.TitleLocation/Agency ResponsibleRetention Period
1.Record of Management RepresentativeManagement Representative3 Years
2.Records of Contract ReviewMarketingTill the customer is in contract
3.List of Approved vendorsPurchase/Management Representative3 Years (updates when ever a new vendor enters into contract)
4.Vendor Development RecordQuality AssuranceTill the vendor is in contract
5.Vendor Audit ReportsQuality Assurance3 Years
6.Approved sub contractors/Vendors performance recordPurchase/QA3 Years
7.Document Distribution/Issue RegisterManagement Representative3 Years
8.Master Formula & Packing  RecordFRD/PD/Quality assurancePermanent Record
9.Equipment logsProduction/Quality Assurance6 Years
10.Validation ReportsQuality AssurancePermanent Record
11.Batch Manufacturing RecordsProduction/Quality AssuranceOne year after expiry of the batch to which it relates or at least five years after certification of the batch by the Qualified person whichever is longer.  
12.Analytical reports for RM, PM and Finished ProductQuality Assurance/Quality Control6 Years
S.No.TitleLocation/Agency ResponsibleRetention Period
13.Stability ReportsQuality control/Quality AssurancePermanent
14.Store recordsQuality Assurance/Warehouse6 Years
15.Balance and Instrument Calibration recordsProduction, Quality Assurance, Quality Control, Maintenance6 Years
16.Technical data of inspection, measuring and test equipmentManagement Representative/Concerned DepartmentsPermanent
17.Internal  Audit ReportsManagement Representative3 Years  
18.Customer complaint RegisterMarketing/Quality Assurance3 Years
19.Record of preventive actionManagement RepresentativePermanent
20Training recordsAll DepartmentsTill the employee is in service +I year
21.Management ReviewManagement Representative3 years
22.Corrective and preventive action  Management Representative3 years
23.E.H.S RecordsManagement Representative5 Years
24.Standard Operating ProcedureAll DepartmentsExisting copy (ies) and one Obsolete copy shall be retained till further revision.
25.Personnel & Medical RecordsAll DepartmentsRetained till the person exists in the factory  
  • Except  where  legislations requires  longer  retention  periods, the complete  records

Pertaining to each batch, including original data such as laboratory work sheets   

    Should  be retained for at least one year after the expiry date of the batch or where there is no expiry date, for six years after the date of the manufacture.

  • Records of complaints should be retained up to the date of expiry + 1 year or I Year after the receipt of Complaint which ever is longer

    Master documents should be properly secured against theft, loss or alteration of information.

    A check should be made to ensure that all the necessary documents have been stored.

 Records should be protected from tampering or loss.

Records may also be retained by computer but the procedures and checks should be followed. Such records shall be progressively backed up using CD writer and the backed up data shall be kept at a location remote from the active file.

RETRIEVAL OF DOCUMENTS: 

 All documents shall be stored in the department in such a fashion that their retrieval is easy. The following system shall be adopted

A total list (may be alphabetical) of documents of all departments shall be made. The list shall contain the following details:

  • The name of the document.
  • Location of availability.
  • Person to be contacted for retrieval if available.
  • Record of documents issued if any for reference purpose and their subsequent retrieval shall be maintained in the register.

Completed batch processing and packaging records must always be kept under lock and key under the control of Q.A.

Retrieval of any important documents should be possible only on proper authorization of Q.A.

DISPOSAL OF DOCUMENTS:

The expired documents shall be destroyed by Q.A. with proper record and authorization by a suitable method such as shredding, burning etc.

Conclusion :

From the above information we have concluded the following points

Documents are very important for any industry and no document means you have not performed or executed the activities.

To maintain all the documents is not the responsibility of Quality Assurance

Every personnel working in pharmaceutical industry should check the documents for its current version.

Old documents shall be made obsolete before made effective of new documents

Documents shall be stored in lock and Key control along with access control and unauthorized entry to document cell shall be avoided and authorized personnel list shall be displayed outside the document cell.

If required individual racks shall be numbered and name of Documents which are available inside the rack shall be displayed and if required document cell tracking shall be maintained in Excel cell which should contains the location of documents.

In case of lack of space the documents shall be packed in shippers and shippers should be labelled from outside with details like Name of Documents, year and shipper number etc.

No old copies or obsolete copies of any documents shall be available in work place.

Reporting of Analytical values and Rounding off the digits


1.       OBJECTIVE 

 1.1      To lay down a procedure for establishing guidelines for reporting of analytical values and rounding off the digits.

2.      RESPONSIBILITY   

2.1      Analytical Chemist – Quality Control  – Responsible for expressing the analytical values and  rounding off the digits as per these guidelines.

2.2 In Charge/His Designee  – Quality Control – Responsible to check the reported values as per SOP.

3.     PROCEDURE                       

3.1 After completion of the analysis, the analytical chemist shall calculate the analytical result in the  work sheet and compare with the stated limits in the specification.

3.2 The calculated analytical values shall be reported in the worksheets, COAs and raw data sheets as  given in the following table:

Methodology for Reporting of Analytical Results:

At the end of the COA mention the expansion of LOQ, LOD and Disregarding value.

 3.2.1    When reporting the results of the Related substances, see the disregarding limits of unknown  impurities and LOD & LOQ limits of known impurities. Do not consider the unknown impurities which are below the disregarding limit.

3.2.2    If the Known impurity is less than the LOD don’t consider for calculation.

3.2.3    If the Impurity value is more than LOD limit and less than the LOQ do not  consider calculating total impurities and individual impurities

3.2.4 Any Known impurity value more than the LOQ limit shall be considered for calculation of total impurities

3.2  If the calculated value(s) contains more digits in the decimal place than that in the stated limit, the digits after decimal place shall be rounded off as described below.

3.2.1 Rounding off shall be done by considering only one digit in the decimal place to the right of the last place in the limit expression as shown in the illustration below.

3.2.2 If the digit is smaller than 5, it shall be eliminated and the preceding digit shall remain unchanged.

3.2.3 If the digit is greater than or equal to 5, it shall be eliminated and the preceding digit shall be increased by one. 

  • Limits are fixed numbers and shall not be rounded off.

Methodology for Rounding off of Analytical Values:

S. No.TestParameterReporting method
1.Related SubstancesMore than 1.0%One digit after the decimal
2.Related SubstancesLess than 1.0% (0.1% – 0.9%)Two digits after the decimal
3.Related SubstancesLess than 0.1% (0.01% – 0.09%)Three digits after the decimal
4.Related SubstancesLess than 0.01% (0.001% – 0.009%)Four digits after the decimal
5.DissolutionOne digit after the decimal
6.Assay in mgTwo digits after the decimal
7.Assay in %One digit after the decimal
8.Content Uniformity in mgTwo digits after the decimal
9.Content Uniformity in %One digit after the decimal

Illustration of Rounding Numerical Values for comparison with requirements

3.3 When the analytical method or test requires quantification, in such cases, the analytical result shall be expressed as observed numerical value.

 3.4 When the analytical method or test does not require quantification, in such cases the analytical result shall be expressed as “Conform” or “does not conform” as the case may be on Certificate of   Analysis.  However, in the work sheet, the actual observation of analysis shall be specified (for example: Less than 50ppm, colour intensity of sample solution is not more than that of standard  solution “x” or formation of specific colour to the solution or formation of precipitate).    

3.5 Analytical values or results for the tests shall be expressed with units as given in Annexure – 1.

4.       ABBREVIATIONS                           

4.1     LOD – Limit of Detection

  • LOQ – Limit of Detection
  • COA – Certificate of Analysis

5.      REFERENCE

Nil

6.     ANNEXURES            

       Nil

Investigation of Out of Trend Results


  1. OBJECTIVE 
  1. To lay down a procedure to investigate an Out of Trend results in the product release.

2.0 RESPONSIBILITY  

    2.1       Quality Control:

Analyst        :  Responsible for reporting OOT result and to carry out the investigation.

Supervisor   :   Responsible for performing Preliminary Laboratory investigation along with the analyst.

Head           :  To initiate and conclude laboratory investigation and ensure compliance as per SOP.                                               

3.0    PROCEDURE   

  • 3.1 An Out of Trend results shall be investigated before releasing the batch.
  • 3.2 Analyst should check the data for compliance with test specifications before discarding test preparations.
  • 3.3 When unexpected results are obtained and no obvious explanation exists, test preparations should be retained, if it is stable.
  • 3.4 An assessment of accuracy of the results should be stated immediately and the same shall be informed to the supervisor.
  • 3.5 Errors like spillage of a sample solution or the incomplete transfer of a sample composite, the analyst should immediately document what happened by Incident.
  • 3.6 Analysts should not be completed the analysis for the sole purpose of seeing what results can be obtained when obvious errors are known.
  • 3.7 Compare the current results with one another, in-between the current batch results. Example: Compare the Content uniformity results each other and the difference between the individual results should not be much difference. And investigate if any value is near to the limit.

3.8 Compare the current results with earlier results.

Examples: Compare the current batch results with previous batch results.

  • 3.9 THE RESULTS CAN BE DIVIDED INTO THREE TYPES AS BELOW
  • 3.9.1 Data as a single result: Assay, pH, average dissolution, and average delivered dose.
  • 3.9.2 Data with multiple results: Dissolution testing and delivered dose uniformity of Dosage units.
  • 3.9.3 Degradation product and impurities data: Also data reported as a single result; however, they are discussed separately because of the nature of the collection and the reporting of data.
  • 3.10 INTERPRETATION OF SINGLE RESULTS
  • 3.10.1 When the results are very close to the limit and it is not justified scientifically or statistically, the test shall be repeated to conform the first result; initial results shall be reported, if the repeated results are with in the specification.
  • 3.10.2  If the repeated results are out of specification then it shall be investigated as per Out of Specification SOP.

  • 3.11 INTERPRETATION OF MULTIPLE RESULTS
  • 3.11.1 If the variations like high standard deviation, any result is border line with specification, and All the results are very close to lower or higher limit, the data shall be reviewed and investigate for the reason.
  • 3.11.2 Before going to S1 investigate in DR, before going to repeat CU shall be investigate.
  • 3.11.3 If the reason is not identified, repeat the analysis to conform the original results.
  • 3.11.4 Initial results shall be report if the repeated results are with in the specification.  If the repeat results are an out of specification then it shall be investigated as per Out of Specification SOP.

  • 3.12 INTERPRETATION OF DEGRADATION PRODUCT AND IMPURITIES DATA
  • 3.12.1 If the results of known impurity or total impurity are very close to the limit while releasing the batch, the investigation shall be carried out, the results can be reported if the results can justified scientifically or statistically.
  • 3.12.2 If the impurity difference is more than 50% from previous batch result, the same shall be investigated. Sample shall be repeated, if it is not justified scientifically.
  • 3.12.3 Initial results shall be report if the repeated results are with in the specification.  If the repeat results are out of specification, then it shall be investigated as per Out of Specification SOP.

3.13 LABORATORY INVESTIGATION

  • Verify the analyst qualification and discuss the test method with the analyst, conform analyst knowledge and performance of the correct procedure.
  • Review the step by step procedure from STP to see if any instruction was omitted or followed incorrectly.
  • Review all raw data obtained in the analysis, including prints and actual values, chromatograms for proper data processing to identify anomalous or suspect information.
  • Verify that the calculations used to convert raw data values into a final test result are scientifically sound, appropriate and correct.
  • Verify if any unauthorized or invalidated changes are made to automated calculation methods.
  • Verify the respective calibration records of the instruments used.
  • Verify that appropriate Reference / Working standards, solvents, reagents and other solutions were used and they meet the required specifications.
  • Verify that special precautions, if applicable, were followed correctly.
  • Verify dilution of samples, if applicable, another two dilutions of the sample should be made and retested for comparison.
  • Verify the preparation of sample and drug dissolved completely.
  • 3.14 OOT NUMBERING SYSTEM

             Allot the OOT number as follows, OOT/YYYY/XXXX, Eg: OOT/2021/0001

             First 3 digits indicates the OOT (Out Of Trend)

             4th digit indicates slash “/” ,  5th to 8th digits indicates year (i.e., 2021)

             9th digit indicates slash “/”

            10th to 13th digits indicates the serial number starts from “0001” for the respective year.

  • 4.0 ABBREVIATIONS   

            4.1     OOS     ®        Out Of Specification

4.2     QC       ®        Quality Control Department

5.0       REFERENCE           

Not applicable

6.0       ANNEXURE

6.1        Annexure-1       →        Laboratory Investigation report for OOT

6.2        Annexure-2       →        OOT Register

ANNEXURE -1

LABORATORY INVESTIGATION REPORT FOR OOT

OOT  Number :
Product / Material Name 
Batch No./ AR .No. 
Stage/ Test/Analysis 
Results 
Limits ( Specification) 
Specification No/ STP No. 
Analyst (Sign & Date)   

                     LABORATORY INVESTIGATION

S.NoCheck listObservation (Yes / No / NA)
 1Analyst trained in the particular test?  
 2Analytical Method adequate and followed properly (step by step)? 
 3Evident from the discussion that the analyst has understood Analytical Method and the Operation SOP of the equipment / Instrument? 
 4Analyst calculated the results using correct potency of the standard? 
 5Analyst calculated the results correctly as mentioned in Analytical Method? 
 6Evident that the suitability requirements of the analytical method were all met? 
 7Any similar occurrence with the analyst earlier? 
 8Any similar histo ry with the product / material? 
 9Proper glassware used for analysis? 
 10Proper volumes of pipettes used for analysis? 
 11Any obvious evidence of glassware contamination? (Visual) 
 12Evidence or probability of the glassware was not washed or dried properly? 
 13Glassware used for analysis properly and legibly labeled? 
 14Any evidence that the sample was not stored properly? 
 15Dilutions made in sample / standard preparation as per Analytical Method? 
 16Environmental conditions (temperature, humidity, light) during analysis appropriate? 
 17Instrument related problems if any noticed? 
 18Are there any samples analysed for the same test together with this failing sample? 
 19If Yes (for the above question), then is there any implication for the results obtained for those samples? 
 20Reagents / chemicals used of recommended grade and prepared as per the analytical method? 
 21Correct standard used for analysis? 
 22Standards, reagents used properly stored? 
 23Any evidence that the standards, reagents were not properly labeled? 
 24Standards, reagents used within their expiration dates? 
 25Evidence that the standards, reagents have degraded? 
 26Evidence that the reagents, standards or other materials used for test were contaminated? 
 27Working standards standardized as per the Analytical method? 
 28Equipment / Instrument used for analysis in calibrated state? 
 29Any evidence of malfunction of the relevant equipment? 
 30Preventive Maintenance Programme of the equipment performed as per schedule? 
 31Appropriate analytical balance used? 
 32SOP adequate and the equipment operated as per SOP? 
 33Instrument / equipment meeting the system suitability criteria mentioned in the analytical method? 
 34Any other Observations / Comments             
Cause assigned    £ Yes            £ No
Evaluation and comments:          
Section In-charge QC (Sign & Date)
Retesting required                                                                £ Yes                                                       £ No
Comments:              
Retested results                                                                 £ Complies                                                  £ Does not comply                                                                                                  
Evaluation and comments:                                
Section In-charge QC (Sign & Date)
Conclusion of Laboratory Investigation :                            
QC In-charge (Sign & Date)
Final Conclusion :
                               
In-charge QA  (Sign & Date)

ANNEXURE-2

OOT REGISTER

S.NODATEOOT NUMBERPRODUCTBATCH NO.A.R.NOTESTREMARKS
          
          
          
          
          
          
          
          
          
          
          

Preventive Maintenance of MILLI -Q Water System


1.         Objective

  1. To describe the procedure for preventive maintenance of MILLI -Q.

2.         Responsibility

  • Executive  – Instrumentation – To perform the preventive maintenance.
  • Head – Quality Control – To ensure compliance against established schedule.

3.         Procedure

3.1       FOR GENERAL CLEANING:

  • Ensure that the power supply to the instrument is switched ‘ OFF’ before cleaning.
  • Clean the external body  with a clean dry cloth .
  • 3.2 OPERATING PROCEDURE:
  • Check the Q- Guard.
  • Check the Quantum Catridge.
  • Check the Millipak.
  • Check the pyrogard D.
  • Flow Calibration has to do if necessary.
  • Check the POU dispenser.
  • A10 UV lamp has to check.
  • Clean the UV lamp.
  • A10 UV  lamp has to calibrate if necessary.
  • 4.0 ABBREVATIONS
  • SOP – Standard Operating Procedure
  • QC – Quality Control

5. 0    REFERENCES

  • Preventive Maintenance Procedure for Laboratory.

6.0   ANNEXURES

Nil 

Preventive Maintenance of Gas Chromatograph (Agilent)


1.0       Objective

1.1       To describe the procedure for preventive maintenance of Agilent   GC

2.0       Responsibility

  • Executive  – Quality Control– To perform the preventive maintenance activity.
  • Head Quality- Quality Control  – To ensure compliance against established schedule.

3.0 Procedure

Precautions:

  1. Ensure that the power supply power supply to the instrument is switched “off” before starting the preventive maintenance.
  2. Clean the instrument with a clean dry cloth every day.

3.1 Performance checks shall be done for the following parameters before doing preventive maintenance

  • 3.1.1 Flow accuracy
  • 3.1.2 Retention Time Reproducibility
  • 3.1.3 Area Ratio Reproducibility
  • 3.1.4 Oven Temperature
  • 3.2 Enter the values in standard maintenance card as per sop

      The following components of GC shall be subjected for preventive maintenance on the schedule date.

  • 3.3 GAS CHROMATOGRAPH
  • 3.3.1 Instrument shall be cleaned from dust with a blower
  • 3.3.2 External gas leaks shall be checked with soap solution , all valves shall be tighten in case any leaks found.
  • 3.3.3 Clean the injector port liner and change the septum
  • 3.3.4 Clean the detector parts with DMA
  • 3.4 HEAD SPACE
  • 3.4.1 Clean the system from dust
  • 3.4.2 Clean the HSS needle or change as and when required.
  • 3.4.3 Check the status of rotor and stator of the HSS valve (sampling)
  • 3.4.4 Check the contamination of transfer line.
  • 3.4.5 Perform stream cleaning of HSS.
  • 3.5 Enter the performance checks and preventive maintenance checks in standard maintenance card as per SOP
  • 3.5.1 Stick the under preventive maintenance label during performing
  • 3.5.2 Enter the preventive maintenance status details as per SOP Preventive Maintenance Programme for Laboratory Instruments..
  • 3.5.3 Frequency of schedule is every 3 months.
  • 4.0 ABBREVATIONS
  • SOP  – Standard Operating Procedure
  • NMT – Not More Than
  • % RSD – Percentage Relative standard deviation
  • 5.0 REFERENCES
  • Calibration of gas chromatograph
  • Preventive Maintenance Programme for Laboratory Instruments.
  • 6.0 ANNEX URES

Nil

Adjustment of Chromatographic Conditions for System Suitability


1.         OBJECTIVE

  1. 1 To lay down a procedure for adjustment of chromatographic conditions for System suitability

2.         RESPONSIBILITY

2.1 Chemist / Executive –QC – To follow the SOP.   

2.2       In Charge / His Designee – QC – To ensure the compliance of SOP

3.         PROCEDURE

3.1    The various parameters of a chromatographic conditions shall be adjusted to  satisfy the system suitability criteria for particular analysis

3.2   The parameters shall be adjusted in order to ensure the separation required for satisfactory performance of the test or assay without fundamentally modifying the method

3.3  The adjustment of critical parameters shall be performed if they are clearly mentioned in the monograph in order to achieve the system suitability

3.4   The adjusting limits of parameters shall be followed as mentioned in annexure-1

3.5   Adjustments shall be permitted only if suitable standards (including reference standards) are available for all compounds used in the suitability test and are used to show that the adjustments have improved the quality of the chromatography in meeting system suitability requirements

3.6 Adjustments of Multiple parameters shall be avoided in order to avoid cumulative effect on the performance of the method.

3.7 The modified parameters shall be recorded in worksheet and method shall be  validated.

  • Adjustments to chromatographic systems performed in order to comply with System suitability requirements should not be made to compensate for column failure or to circumvent replacing a deteriorated column.
  • Adjustment of the various parameters in reverse phase liquid chromatographic methods will not always result in satisfactory chromatography. In that case, it may be necessary to change the column with another of the same type but from a different manufacturer.

4.     ABBREVIATIONS                                                  

4.1    QC – Quality Control.

5.     REFERENCES

  • British Pharmacopoeia
  • United states pharmacopoeia forum

6.         ANNEXURES

6.1       Annexure-1     Limits for adjusting parameters for system suitability

ANNEXURE – 1

Limits for Adjusting Parameters for System Suitability

ParametersThin Layer chromatographyHigh performance Liquid chromatographyGas chromatography
Composition of Mobile Phase.The amount of minor component  may be adjusted by ± 30% relative or ±2% absolute, whichever is larger .No other component is altered by more than 10 % absoluteThe amount of minor component may be adjusted by ± 30% relative or ±2% absolute, whichever is larger .No other component is altered by more than 10 % absoluteNot Applicable
pH  of mobile phase±0.2 pH, unless otherwise stated in the monograph or ± 0.1 pH for neutral substances±0.2 pH, unless otherwise stated in the monograph or ± 0.1 pH for neutral substancesNot Applicable
Concentration of salts in the buffer component of Mobile phase± 10%± 10%Not Applicable
Detector Wavelength Not ApplicableNo adjustment  permittedNot Applicable  
Stationary phaseAs Mentioned in monographColumn length :  ± 70 % Column I.D     :   ± 50 % Particle size     :   Maximal                              reduction of 50 %                              No  increase                               permittedColumn length :  ± 70 % Column I.D     :   ± 50 % Particle size     :   Maximal                              reduction of                             50 %,No                              increase                             Permitted Film Thickness  – 50 % to 100%
Flow RateNot Applicable± 50 %± 50 %
ParametersThin Layer chromatographyHigh performance Liquid chromatographyGas chromatography
TemperatureNot Applicable± 10 % , to a maximum of 60° C± 10 %
Injection volume / Application volumeDecreased to 20 % of the prescribed Volume if using fine particle size plates ( 2-10 micron)May be decreased, provided detection and repeatability of the peaks to be determined satisfactoryMay be decreased, provided detection and repeatability of the peaks to be determined satisfactory
Column temperatureNot ApplicableCan be adjusted by as much as ± 20°. Column thermo stating to improve control and reproducibility of retention timeCan be adjusted by as much as ± 2 % in terms of absolute temperature
Oven temperature program  Not ApplicableNot ApplicableCan be adjusted by as much as ± 2 % in terms of absolute temperature. For the times specified for the temperature to be maintained or for the temperature to be changed from one to another, an adjusted of upto ± 20% is permitted

Good Chromatography Practices in Quality Control Laboratory


1.0       OBJECTIVE 

             1.1        To lay down a procedure for Good chromatography practices in Quality control Laboratory.      

2.0       RESPONSIBILITY   

             2.1      Chemist / Executive – Quality Control – to follow the procedure.

             2.2      Group leader / Supervisor – Quality Control to ensure adherence to the procedure.

             2.3      Head – Quality Control for implementation and compliance.  

  • 3.0 PROCEDURE           
  • 3.1 HPLC MOBILE PHASES:
  • Milli – Q water and HPLC grade solvents shall be used for the preparation of mobile phase.
  • The mobile phase for the HPLC analysis shall be prepared as per the composition and pH(If  any) described in the Standard Testing Procedure (STP).
  • Allot the A.R. No. of the sample under analysis as the Reference Number for the mobile phase
  • Record the preparation details of the mobile phase in the respective record of analysis or in respective work sheet of the sample under testing.
  • Label each mobile phase after its preparation.
  • The mobile phase shall be filtered and sonicate and visually check for clarity before use.
  • The mobile phase shall be discarded if any precipitation or hazy-ness is observed visually.
  • Use the mobile phase within the validity period mentioned in the test procedure. If no validity period is mentioned then use it within 48 hours.
  • 3.2 STANDARD PREPARATION:
  • The standard preparation shall be made as per the STP, taking into consideration the analyte stability & storage requirement.
  • Bracketing Standard shall be handled as per SOP    

3.3 SYSTEM SUITABILITY:

  • System suitability shall be established as per STP and SOP No.QC097 (Adjustment of Chromatographic conditions).
  • System suitability/system precision of the standard shall be established with successive injections.
  • The system suitability shall also be verified in the form of system suitability solution or bracketing standard if there is any time gap between the analyses.
  • After completion of chromatographic runs of initial system suitability requirement, if there is a delay in running samples at any stage where the time gap from the last established standard run’s acquisition time (of initial system suitability runs or the last bracketing standard, whichever is the latest) is not exceeding 12 hours, then the system shall be continued by running appropriate.
  • Bracketing standard first and establishing the system suitability parameters as indicated in the current version of SOP .       
  • 3.4  SAMPLE PREPARATION:
  • All sample preparations shall be prepared as per the method given in the respective STP, taking into consideration the analyte stability & storage requirement.

3.5   CHROMATOGRAPHY ANALYSIS:

  • Analysts shall perform analysis of samples after they are qualified and certified as per Standard Operating Procedure
  • Follow safety instructions carefully all the time.
  • SOPs and logbooks must be maintained at the workplace where it can be easily accessed.
  • Update all relevant logbooks concurrently.
  • Label all test and standard preparations for all tests with at least details such as A.R. No.,                                 solution name and appropriate replicate preparation number wherever is applicable (in a suitable short form incase of space constraint but in an identifiable manner), sign and date with legible marker pen.
  • Label vials of GC/ LC analysis using a legible marker pen for as follows XYY, where ‘X’ is the unique quick set or the sample set number (in a suitable short form incase of space constraint but in an identifiable manner) and ‘YY’ is the position at which that vial is to be placed.
  • Before starting a sample set, ensure the system suitability (other than %RSD) in single injection mode, make adjustments if necessary for achieving system suitability. Once system suitability is achieved run the complete sample set including the system suitability injection.
  • All the single / trial injections shall be processed and documented as disregarded chromatograms.
  • The disregarded chromatograms shall not be considered for calculations and shall be stamped or written as “DISREGARDED”. The reasons for disregarding of the chromatogram shall be documented.
  • The disregarded chromatogram shall be filed along with the test chromatograms
  • During chromatographic analysis, use blank determinations at appropriate intervals to  confirm and ensure baseline stability verification and carry over contaminations.
  • Label all known peaks such as peak due to blank, placebo, known impurities and analyte in chromatograms obtained with blank, system suitability, first standard run of the RSD determination sequence, first trial of sample and each bracketing standard.
  • Attach all relevant analytical raw data obtained from instruments such as High Performance Liquid Chromatograph, Gas Chromatograph to the work sheet.
  • Retain all solutions used in the analysis for tests to determine unit dose quality such as Uniformity of Dosage Unit, Content Uniformity, Dissolution and equipment cleaning
  • samples for content of active ingredient (store on bench top or in refrigerator as mentioned in  the standard test procedure based on the solution stability) until analytical results are determined so as to facilitate Incident / Out Of Specification investigation.
  • Report all incidents and failures to the supervisor as soon as possible and follow instructions.
  • If any measured bracketing standard is not meeting the acceptance criteria, raise incident as per the current version of the and determine the status of result based on the disposition comments made by Head QA.
  • After completion of chromatographic runs of initial system suitability requirement,  if there is a stoppage of the system due to any reasons, then raise a ‘Incident’ as per the SOP (Reporting of  Incidents in Quality control Laboratory). If the time gap from the last established standard run’s acquisition time (of initial system suitability runs or the last bracketing standard, whichever is the latest) is not exceeding 12 hours, then the system shall be restarted (re run) by running appropriate Bracketing standard first and establishing the system suitability parameters as indicated in the SOP Bracketing Standards and any other system suitability parameters if any instructed by the supervisor. If the stoppage is due to removal of Column, change or addition of freshly prepared mobile phase to the existing volume, then the analysis shall be restarted and continued of after establishing initial system suitability parameters as per respective Analytical Method or STP.
  • All the digits appearing on the chromatogram shall be taken as such for calculation.
  • Reprocessing of chromatograms, if necessary, at a later date/time shall be documented with reason(s) for reprocessing.

   4.0   ABBREVIATIONS                                  

  • GC                   –      Gas chromatography.
  • HPLC               –       High performance liquid chromatography.
  • STP                  –      Standard Testing Procedure.
  • QA                   –      Quality Assurance.
  • A.R. No.          –     Analytical Reference Number.
  • LC                     –     Liquid chromatography.
  • OOS                  –     Out of specification.
  • SOP                   –     Standard Operating Procedure.
  • QC                     –    Quality control.

5.0     REFERENCES    

5.1        Adjustment of chromatographic conditions

5.2        Bracketing of Standards during content Uniformity, Assay, Dissolution, Related substances, Organic volatile impurities and Residual solvents.

5.3       Qualification of analyst in quality control

5.4      Reporting of incidents in quality control laboratory

6.0    ANNEXURES                     

Nil