Cleaning of HPLC columns

1.0    Purpose   :   To provide an instruction for washing of HPLC columns.

2.0    Objective :   To provide a documented procedure for washing of HPLC columns.

3.0    Scope      :  This procedure is applicable for washing of HPLC columns in QC Department.

4.0     Responsibility   :

·        Primary  :    QC Chemist / QC-Officer

·        Secondary  :  Overall QC – In charge

5.0      Procedure  :

·        After completion of analysis stop the pump, keep the reservoir in the distilled & filtered water.

·        Open the purging valve of the pump; purge the system for 3 to 5 minutes to remove air bubbles. Close the purging valve by decreasing the flow rate up to zero.

·        Wash the HPLC column initial with HPLC grade water for about 15-20 minutes.

·        Then wash the HPLC column with respective solvent mixtures (e.g. 50:50 Methanol: Water or Acetonitrile: Water) for minimum ½ hr to 1 hr.

·        Finally wash the HPLC column with respective solvent (Acetonitrile / Methanol) for about 15-30 minutes.

·        Keep flow rate 0.5 ml / min or 1.0 ml / min. increase flow rate gradually.

·        Check the pH of eluent on pH paper (it should be neutral) 

·        Store the HPLC column in solvent (acetonitrile or methanol).

·        Disconnect the HPLC column and keep it at respective column storage box.

·        Maintain the cleaning record in HPLC column logbook.

Functions of Quality control department

1.0        Purpose   : To provide an instruction for functions of quality control department.

2.0        Objective: To provide a documented procedure for functions of quality control department.

3.0        Scope      :   This procedure is applicable for functions of quality control department.

4.0        Responsibility  :

·       Primary: QC Chemist / QC-Officer

·       Secondary : Overall: QC – In charge

5.0      Procedure  :

·         List of activities of quality control department.

Ø      Testing and release or rejection of all incoming raw materials, packing materials, in-process / intermediates and finished products as per specified specifications.

Ø      Maintaining testing records as per standard procedures for raw materials, packing materials, in-process / intermediates and finished products.

Ø      Calibration of laboratory instrument / equipment.

Ø      Performing stability study.

Ø      Control sample storage.

Ø      Analytical method validation.

Ø      Preparation of standard volumetric solutions and maintain standardization record.

Ø      Maintain Labeling procedure at all the stages and records.

Ø      Maintain working / reference standard record of products.

Ø      Analysis of complaint samples as and when required.

Ø      To conduct technical audit / self-inspection.

Ø      Follow safety norms at all the stage during handling of chemicals and using instruments.

Ø      Follow good laboratory practices

Labeling by Quality control department

1.0        Purpose    :  To provide an instruction for labeling by quality control department.

2.0        Objective  : To provide a documented procedure of labeling by quality control department.

3.0        Scope: This procedure is applicable for labeling by quality control department.

4.0        Responsibility  :

·       Primary     :   QC Chemist / QC-Officer

·       Secondary  : Overall: QC – In charge

5.0      Procedure  :

·        ‘UNDER TEST’ label.

Ø    Under Test labels shall be affixed on each packs of raw materials / packing.     

Ø      Colour of the label is Yellow.

·       ‘SAMPLED’ label.

Ø     Sampled labels shall be affixed on the container of raw material / packing materials pack from which the sample is drawn by QC Chemist.

Ø     Colour of the label is Orange.

·       ‘APPROVED’ label.

Ø     Approved labels shall be affixed on each container / pack after materials / product is approved by QC Chemist.

Ø     Colour of the label is Green.

·          ‘REJECTED’ label.

Ø      Rejected labels shall be affixed on each container / pack after materials / product is rejected by QC Chemist.

Ø      Colour of the label is Red

Record maintained by Quality control department

1.0     Purpose   :  To provide instructions for record maintained by quality control department.

2.0     Objective :  To provide a documented procedure for record maintained by quality control department.

3.0        Scope  :  This procedure is applicable for record maintained by quality control department.

4.0        Responsibility  :

·       Primary        :     QC Chemist / QC Officer

·       Secondary    :      Overall : QC In Charge

5.0      Procedure   :

·       Following are control documents.

Ø            Standard Operating Procedures of Quality Control Department..

Ø            Specifications of Raw material.

Ø            Specifications of Packing material.

Ø            Specifications of In-process / intermediate.

Ø            Specifications of Finished product.

Ø            Standard Test Procedures of Raw material.

Ø            Standard Test Procedures of Packing material.

Ø            Standard Test Procedures of In-process / intermediate.

Ø            Standard Test Procedures of Finished product.

Ø            List of Instruments.

·        Following are records.

Ø            Raw materials testing records.

Ø            Packing materials testing records.

Ø            In-process / intermediates testing records.

Ø            Finished products testing records.

Ø            Instrument calibration records.

Ø            Stability study records.

Ø            Instrument calibration records.

Ø            Glassware calibration records.

Ø            Raw material inward logbook

Ø            Raw material work sheet issuance logbook.

Ø            Intermediate inward logbook.

Ø            Intermediate work sheet issuance logbook.

Ø            Finished product inward logbook.

Ø            Finished product work sheet issuance logbook.

Ø            In process samples inward logbook.

Ø            Instrument uses logbooks.

Ø            HPLC column logbook.

Ø            Stability chamber logbook.

Ø            Laboratory cleaning logbook.

Ø            Volumetric solution logbook.

Ø            Standard reagent solution logbook.

Ø            Indicator logbook.

Ø            Retention sample logbook.

Ø            Logbook issuance logbook.

Validation of QC Chemist

1.0     Purpose    :   To provide an instruction for the validation of QC Chemist.

2.0     Objective  :   To provide a documented procedure for the validation of QC Chemist.

3.0       Scope     :  This procedure is applicable for QC Chemist .

4.0     Responsibility  :

·       Primary      :  QC Chemist / QC-Officer

·       Secondary :  Overall: QC – In charge

5.0     Procedure    :

·       Following method used for the validation of QC Chemist to confirmed his / her analytical skills.

Ø         QC In-charge identifies a previously analyzed and approved batch sample.

Ø         Identified batch sample shall be coded and hand over to QC Chemist with all the   details of test procedure.

·       QC Chemist qualified on the criterion as follows:

Ø            QC Chemist performs the analysis and documents the result as per Good             Laboratory Practices.

Ø            QC Chemist performs the analysis and meets the acceptance criteria as per below   mentioned table.

Ø            The QC Chemist working in laboratory shall be qualified on one or more tests as required by the QC In-charge.

Ø            The QC Chemist shall be qualified once a year.

Ø            A record shall be maintained.

Ø            Incase of QC Chemist fails to meet the criteria, the QC Chemist shall be trained and re-qualified. The training record shall be recorded

                Acceptance Criteria for Chemist Validation

Sr. No.	Test	Acceptance Criteria
01	Assay test by HPLC	% RSD of Retention Time and Area of six replicate injection should not more than 2 %
02	Impurity test by HPLC	% RSD of two replicate injection for highest impurity should not more than 10 %
03	IR test	Three separate analysis, which shall be concordant with each other.
04	Water / LOD test	% RSD of triplicate analysis should not more than 2 % 10 % moisture / LOD range 0 to 0.5 %  5 % moisture / LOD range 0.5 to 2.0 %  2 % moisture / LOD range 2 % above
05	UV test	% RSD of three replicated absorption of solution of particular concentration at specified wavelength should not be more than 2 %
06	GC test	% RSD of Retention Time and Area of six replicate injection should not more than 2 %
07	Sp. Gravity test	% RSD of six replicates reading should not more than 2 %
08	Specific Optical Rotation test	% RSD of six replicates reading should not more than 2 %
09	Assay by chemically test	% RSD of six replicate analysis should not be more than   2 %

Analytical report numbering

1.0    Purpose   :  To provide an instruction for analytical report numbering procedure (AR No.)

2.0   Objective  :   To provide a documented procedure for analytical report numbering.

3.0   Scope  :    This procedure is applicable for analytical report numbering in QC department .

    4.0    Responsibility  :

·        Primary     :   QC Chemist / QC-Officer

·        Secondary  :   Overall: QC-Officer

5.0    Procedure:

·        Analytical Report Numbering for Raw Material

Ø      Numbering of analytical report of raw material shall be in the form of R-XXX/YY/ZZ

          For Raw material: R-XXX/YY/ZZ(e.g. R-001/09/09)

              Where, R = raw material

                    XXX = serial no. (e.g. 001, 002,)

                      YY =month.

                      ZZ  = year (e.g. 2009 as 09)

·        Analytical Report Numbering for Packing Material

Ø      Numbering of analytical report of packing material shall be in the form of P-XXX/YY/ZZ.

          For Packing material: P-XXX/YY/ZZ (e.g. P-001/08/09)

              Where, P = packing material

                     XXX = serial no. (e.g. 001, 002…)

                      YY =  month.  (e.g.01,02..  )

                                          ZZ   =  year (e.g. 2009 as 09)

·               Analytical Report Numbering for Intermediate

Ø      Numbering of analytical report of intermediate shall be in the form of

      I-WWW/XXX/YY/ZZ.

          For Intermediate: I- WWW/XXX/YY/ZZ (e.g. I-001/001/01/09)

             Where,           I      =  Intermediate

                            WWW   =   product code (001, 002, ….)

                             XXX    =   serial no. (e.g. 001, 002, ….)

                           Y Y    =   month. (e.g.01,02..  )

                               ZZ     =    year (e.g. 2009 as 09)

·               Analytical Report Numbering for Finished Product

Ø      Numbering of analytical report of finished product shall be in the form of XXX or WWW or WW//XXX/YY/ZZ

          For Finished product:   WWW or WW/XXX/YY/ZZ  (e.g.  MBZ/001/01/09)

          Where,           WWW or WW       = Short name of product (001, 002, ….)

                                      XXX = serial no. (e.g. 001, 002, ….)

                                                             YY =  month (e.g.01,02..  )

                                                 ZZ  =  year (e.g. 2009 as 09)

·               Analytical Report Numbering for Re-testing Raw Material   

Ø      Numbering of analytical report of re-test raw material shall be in the form of                        R-XXX/ZZ/R1.

          For re-test Raw material: R-XXX/ZZ/R1 (e.g. R-001/09/R1)

          Where,      R         = raw material

                       XXX         = serial no. (e.g. 001, 002, ….)

                         ZZ           = year (e.g. 2009 as 09)

                                              R1         = re-test first time (e.g. R1, R2, ….)

·               Analytical Report Numbering for Re-testing Intermediate

I- WWW/XXX /ZZ/I1

          For Intermediate: I- WWW/XXX/ZZ/I1 (e.g. I-001/001/09/I1)

           Where,        I        = intermediate

                          WWW   = product code (001, 002, ….)

                          XXX      = serial no. (e.g. 001, 002, ….)

                             ZZ       = year (e.g. 2009as 09)

                                              I1           = re-test first time ( e.g. I1, I2, ….)

Out of Calibration of instruments

1.0 Purpose : To provide a procedure for the action to be taken in the event of out of Calibration of instruments.

2.0 Objective  : To provide a documented procedure for the action to be taken in the event of out of Calibration of instruments.

3.0      Scope     :   Applicable to QC/QA Department.

4.0    Responsibility  :

·       Primary        :     QC Chemist / QC Officer

·       Secondary    :      Manager QC/ Manager QA

5.0      Procedure   :

·       Following actions should be taken in the event of out of calibration status of instruments.

Ø      Inform the head of the QC department and affix a status label 'OUT OF CALIBRATION'.

Ø      Inform the Maintenance department to carry out in-house rectification of the instrument.

Ø      If the in-house maintenance department can rectify the defect, then use the instrument after proper calibration.

Ø      In case in-house maintenance department is unable to rectify the defect, call the supplier / manufacturer of the instrument.

Ø      Once the said instrument is repaired then carry out calibration and ensure that it is working satisfactorily.

Ø      If the external expert performs the servicing satisfactorily, use the instrument after calibration for routine analysis.

Ø      If the external expert fails to rectify the instrument, affix a status label ' OUT OF ORDER'.

Ø      Arrange to replace the instrument.

Ø      In case an instrument is found out of calibration then the results of previous calibration are reviewed.