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Working Standard Qualification Procedure

Guideline for Laboratory Standard Management (Preparation, Qualification and Handling of Analytical standards/Working Standard/Primary Standard etc.)

Working Standard Management

1.0   Objective :

    • To lay down a procedure for the Preparation, Qualification and Handling of Analytical standards (Working Standard, Reference Standard & Primary Standards).

2.0   Scope :

    • This SOP is applicable in Quality Control for the Preparation, Qualification and Handling of Analytical standards(Working Standard, Reference Standard & Primary Standards).   

3.0   Procedure – Working Standard Management

    • Types of Analytical standards Used in Quality Control Laboratory
      • Reference standards
      • Working Standards
      • Primary Standards

  • Reference standards Management:

    • Reference standard may be Pharmacopoeial or non Pharmacopoeial.
    • Standards are authentic standards received from pharmacopeia Commissions or R&D labs.
    • The availability status of current lot of reference standard is checked from Current catalogues of Pharmacopeia commission or through the supplier.
    • Review the status of the reference standards once in two months for USP, Ph. Eur, BP,IP and record the validity of available reference standard as per Annexure-XIII

    • Handling, storage and destruction of Reference standards:

    • On receipt of the Reference standard, check the invoice, delivery note, MSDS, COA’s [if available] .
    • QC officer/designee records the receiving and issuance of Reference standard in the Annexure V.
    • Store Reference standards at a temperature between 2°C and 8°C securely, unless otherwise specified.
    • Allow the reference standard vial to attain ambient temperature and wipe the outer surface of the vial with tissue paper before use.
    • Record all consumption details in reference standards usage log as per Annexure-VIII.
    • Whenever possible use less quantity of reference standard or impurity by altering the dilutions so that the final concentrations of the standard solutions remain same.
    • For related compounds and impurity standards that are not easily available prepare standard stock solution.
    • Use this standard stock solution for qualitative tests only i.e. Resolution, identification, tailing, theoretical plates etc.
    • Label the stock solution as per Annexure-XII , document the solution as per Annexure–XV and record the usage details in Annexure XVIII .
    • Discard the solution if solution becomes hazy or system suitability criteria not achieved as per requirement.
    • Stop the usage of Reference standard once it is removed from catalogue, if any change is observe in the physical properties of reference standard, expired or made obsolete.
    • Remove it from regular stock and discard the material as per destruction procedure. Enter the destruction details in the Reference standards usage log as per Annexure–VIII.
    • Retain the original label of Reference standard after use or expiry of reference standards.

  • Qualification of Working Standard:

    • These are substances to be used as a substitute for official reference standards for routine analysis.
    • Working standards are the standards that are qualified against the current lot of Reference standards.
    • Working standards are to be prepared from approved material.

    • Perform following tests for qualification of working standard:

      • Description,Reference _Working Standard
      • Identification (By IR or HPLC),
      • Loss on drying / water content ,
      • Assay and
      • Related substances.
    • Do not standardize the material of same batch number for more than two times.
    • If approved material is not available, procure the material from approved vendor and standardized against reference standard.
    • Cases in which one material is to be qualified for more than one Pharmacopoeia status i.e. for USP as well as EP, assay shall be performed by all Pharmacopoeia method under consideration.
    • Material should be analysed either at the time of release or at the time of qualification of working standard for all the parameter as per specification of all the Pharmacopoeia consideration.
    • Among all the observed value of assay, average assay value should be reported and used for all the calculation.
    • In case STP & SPC is not available follow Pharmacopoeial method for standardization of working standard.
    • Prepare a Protocol for Evaluation of Working standard as per the specimen mentioned in Annexure-I.
    • Get it approved by Head–QC or designee.

    • Allot a unique identification number to each working standard.

    • To get the approved raw material from ware house department, QC chemist shall prepare a material requisition note and submit to ware house in charge.
    • Ware house personnel shall dispense the material on the basis of material requisition.
    • The dispensing activity shall be performed from approved stock by ware house personnel in a cleaned container and handover to quality control laboratory.
    • Transfer the quantity required for testing (standardization) into cleaned container and stores the remaining portion at a temperature between 2°C to 8°C unless otherwise specified.
    • Store the sample withdrawn for the testing also at the same temperature during standardization.
    • If reference standard is not available (in case of non Pharmacopeia materials) then standardize the working standard against the Standard provided by manufacturer of active pharmaceutical ingredient or reference standard developed by NABL certified laboratory.
    • If reference standard is received from outside lab then characterization data along with COA shall be received from the outside lab.
    • In case if IP/BP reference standard is not available, use USP/EP reference standard for standardization of working standard.
    • In case non- Pharmacopeial working standard is required to use, raw data of analysis such as IR and other related parameter shall be received from the vendor. Incase Pharmacopeial working standard is required, identification shall be done prior to use.
    • Perform the test parameters as defined in protocol.
    • Perform Water content/LOD in Triplicate and report the average value.

  • The acceptance criteria for water content/LOD shall be follows:

Limit of water Content/LOD of the material Relative standard deviation
Up to 1.5% Not more than 15%
1.5% to 3.5% Not more than 10%
3.5% and above Not more than 5%
    • Perform the assay six times (6 samples analysis as mentioned according to standard testing procedure) and report the mean. The result obtained must be within the specification limits.
    • The relative standard deviation of six assay values should not be more than 1.0%.
    • Follow method of analysis as per in-house validated Standard test procedure or as per respective pharmacopeia method.
    • If the method of analysis is by titrimetry or spectrophotometer, finished product HPLC method of analysis can be followed if available.
    • Perform all remaining parameters as per STP or respective pharmacopeia method.
    • Calculate and report the assay/purity/potency finally as “Potency on dried / anhydrous basis”.
    • For routine analysis, vial label shall contain “as such” potency and COA shall be containing both “as such” and “dried or anhydrous” basis potency.

    • If Potency is more than 100% then report potency as 100%.

    • Prepare the Certificate of Analysis for working standard as per Annexure-III and calculation sheet as per Annexure-II..
    • Consider the date of analysis (standardization) of working standard as a starting point for calculating the validity period.
    • Allocate the shelf life of working standard based on Chemistry, stability data or retest/ expiry date provided by the manufacturer of the material.
    • In any case the validity period for any working standard shall not exceed more than 12 months.
    • Once working standard is approved, update the computerized list of working standards as per Annexure-VI.
    • Whenever a vial is issued for use, enter the details in working standard stock card as per Annexure–IX.
    • Maintain separate stock card for each working standard.
    • After certification, dispense the quantity into clear transparent /amber colored (Essentially Use amber colored vials for light sensitive standard) vials in a clean area and caps the vials.
    • Transfer an amount equal to the quantity required for one month usage in each vial.
    • Label working standard vial as per Annexure–IV.

    • Prepare total 14 vials. 12 vials assigned for 12 months or as per validity period.

    • Each vial shall contain the quantity required for one month usages i.e., fill approximately 1 to 5 grams in each vial and one master vial is additional spare which contains approximately 5 to 10 grams.
    • Master vial will come into use in case, running vial is damaged /absorb moisture/exhausted and if quantity for  use remain  less in running vial then transfer required quantity in that vial from master vial.
    • Quantity of working standard  (For example Methylcobalamin etc.) in the vials can be reduced depending upon the requirement.
    • For Vitamin D3, prepare 120 working standard vials and fill approximately 50 mg in each vial .one vial is used for single time analysis.
    • Store all working standards at 2 to 8ºC
    • The validity of a working standard vial is one month from the date of opening.
    • Allow the working standard vial to attain ambient temperature and wipe the outer surface of the vial with tissue paper before use.
    • Receive working standards from other Laboratories along with relevant documents and make entries in the Inward Register for Working Standards as per Annexure–X.
    • Remove the working standard vials from routine use, once its validity is completed and discard as per samples discard procedure and enter into the respective logs.
    • A list for procurement of reference standard should be prepared before two month of expiry of working standard and same shall be maintained as per Annexure-XIV. (E.g. suppose if a working standard is expire on month of August, then a check list for same shall be prepared as per Annexure-XIV in the month of June.)
    • Use the potency of reference standard as specified on the CoA, label/catalogue. if the potency is not mentioned consider the potency as 100 %.

  • Usage of Working Standard :

    • Before using the analyst should confirm that the working standard is current lot.
    • Check the label for that the material is within the expiration period.
    • Open the door of balance, put the butter paper and wait till the balance stabilizes.
    • Dispense the working standard and note this quantity in “Dispense Quantity” column given in Annexure- XVII.
    • Discard the extra working standard (if dispensed) and print the quantity weighed.
    • Transfer the working standard in volumetric flask and put the butter paper back on balance.
    • Take the print of residual quantity and calculate the final transfer quantity by using printer options.
    • Write the final transfer quantity in “Transfer Quantity” column given in Annexure-XVII.

    • Calculate the discarded quantity of working standard by using the formulae as below:

Discarded Quantity = Dispensed Quantity – Transferred Quantity

    • Write the discarded quantity of working standard in “Discard Column” given in Annexure- XVII.
    • “About” indicates the quantity within 10%.
    • Record the other details of working standard in logbook as per Annexure No: XVII
    • During usage of working standard, precaution should be taken such that content of the vials are not contaminated with other products or any spillage should not occur.
    • All apparatus to be used clean and dry.
    • Use the potency of working standard as stated on the label.
    • If the working standard is kept in refrigerator then keep it in the desiccators for 15-30 min to attain room temperature before use.
    • When working standard is required to be dried before use it should be performed at the time of use.
    • For that transfer an adequate amount of the standard to a clean and previously dried vessel, and dry the specified conditions.
    • Do not use the original container as the drying vessel.
    • Discard any unused material.
    • Do not return the material into original container.
    • Where the titrimetric determination of water is required at the time a standard is to be used, proceed as directed by pharmacopoeia /specification.
    • Close the working standard vial after use and keep it in the designated place.
    • Liquid working standard are to be stored at ambient temperature or as specified on the label.
    • Quantitatively transfer the required volume or weight, as appropriate, from the container taking care not to introduce contamination.
    • Do not return unused liquid or drain pipettes back into the container.
    • Pharmacopeial Reference Standard/ Qualified Working Standard of Vanillin, Acetanilide, Sulfanilamide and Caffeine shall be used for calibration of Melting Point Apparatus.

  • Primary Standards:

    • Procure the Primary standards along with Certificate of Analysis (COA) from the manufacturer or supplier.
    • Pure grade materials procured from Sigma-Aldrich, Fluka, Merck, Spectrochem, Loba chemie, Qualigens and Rankem are to be used as Primary Standards. Primary standard shall be used without standardization.
    • Results given in the certificate of analysis of manufactures/Label claim shall be taken as the potency of the standard.
    • Whenever a primary standard receives, allot an identification number according to procedure.
    • Label the bottle with the current version of label when bottle is received.
    • Fill the label with sign and date and expiry date from the date of receiving and fill opening date at the time of open.
    • Update the list of primary standards whenever a new material introduced as per Annexure-VII.
    • The Validity of Primary standards shall be two years from the date of receiving or expiry date mentioned on COA whichever is earlier.
    • Dispense the primary standards in bottles for routine use and label as per Annexure- XI.
    • Replace primary standards in use with fresh quantity from the stock bottle every three months or when the quantity gets exhausted whichever is earlier and record the detail in Annexure –XVI.
    • Discard the primary standards after expiry
    • For calibration of the instruments Pure grade materials procured from Sigma-Aldrich, Fluka,Merck, Spectrochem, Loba chemie, Qualigens and Rankem etc.shall be used .
    • Results given in the certificate of analysis of manufactures/Label claim shall be taken as the potency of the standard.
    • Usage details of primary standards/GC standards/calibration standards shall be recorded in annexure XIX.

4.0   Reference

    • In-house
    • USP

5.0   Annexure – Working Standard Management :

Annexure–I : Protocol for Qualification of working standard

Reference standard details:

Name of the Standard:

Category     : Reference standard /working standard

Grade          : USP/BP/EP/JP/IP/IH                                        Potency:

Lot No         :                                                                           Validity/Expiry:

Details of material under qualification:

Material name    :                                                                    A.R. No. :

Batch No            :                                                                    Source:

Retest/Expiry      :                                                                    Quantity required:

Details of working standard:

Test to be performed              : Description / LOD/ water content / Identification /Assay / Related substances

Working standard No. :                       

No. of vials to be made           :

Storage conditions                  :

Validity of working standard    :

Validity of open vial                  :

Any special instructions           :

Remarks (if any)                      :

Annexure–II : Calculation Sheet for working Standard

           W.S. Name:                                                                                            W.S. No.:

Description :
Identification :                                                                         Inst. ID.                             Cal due date
LOD /Water:                                                                             Inst. ID.                            Cal due date
Related Substances:                                                              Inst. ID.                              Cal due date
Assay                                                                                             Inst. ID.                              Cal due date
Average=
% RSD=
Assay ( As such basis)=
Assay (On dried basis/on anhydrous basis)=

Annexure–III : COA of  Working Standard

Item Name                    :

Evaluated with              :                                                  Batch No. /Lot No.   :

Working Standard No.  :                                                A.R. No.                   :

Source                          :                                                   Source Batch No.    :

Mfg. Dt.                         :                                                  Exp. Date                :

Evaluation Dt.            :                                                   Valid up to              :

Test Procedure             :
TEST REQUIREMENT RESULTS
 Remarks :

Annexure–IV : Label of Working Standard

Working Standard
Name : …………………                          Vial No.:………………

Batch No.: ……………..                         A.R. No.:………………

Mfg. Date: ……………..                         Exp. Date.:…………….

Potency : ……………….                         Water/LOD:…………….

Valid From: …………….                        Valid up to:……………..

Opening Date: …………                         Used before: ………….

Prepared By:……………..                       Checked By…………….

Annexure–V : Inward register for reference standards

Date of receipt

 Name of Reference Standard Source Quantity received (No. of vials x Qty) Lot No. Validity Storage conditions Vial issued on Vial issued By

Remarks

Annexure–VI : List of working Standards

Date of Preparation

          Name of WS Manufacturer

B.No.

 WS No. Qty. Prepared (No. of usage vials x Qty) Valid up to Potency LOD/Water

Remarks

Annexure–VII : List of Primary Standards

Name of  Standard PS No. Manufacturer/B.No. Opening date Use before Remarks

Annexure–VIII : Reference Standards Usage log

Date

 Quantity weighed  (mg) Balance Quantity

(mg)

 Name of product  A.R.No./ B.No. Test Name Used By

Checked By

Annexure–IX : Working Standard Stock Card

Working Standard Name:                                                            Date of Evaluation:

W.S. No.:                                                                                             Valid up to:

Storage Conditions:                                                                          Total Vials:

ISSUANCE DETAILS

Vial No.

 Date of opening Valid up to Destroyed on Destroyed By

Remarks

Annexure–X : Inward register for working standards received from other laboratory

Date of receipt

 Name of Working Standard Quantity received (No. of vials x Qty) Lot No. Validity Storage conditions

Remarks

Annexure–XI : Label for Primary Standard

Primary  Standard
Name :
B.No./Lot No Use Before :
CPS No. Potency :
 Dispensing date: Vial valid up to:
Storage conditions:

Annexure–XII : Label for Stock solution

Stock solution
Product Name  
Name  of Solution  
Stock solution No.  
Stage  
Storage Condition
Preparation Date
Valid upto
Prepared By
Checked by

 Annexure–XIII : Validity Check list for reference Standards

Source: USP/Ph.Eur/BP/IP/_______________

Sr. No.

 Name of Reference Standard Lot No. Lot valid or not Validity Verified By

Remarks

Annexure–XIV : Check list for procurement of reference standard

Sr. No. Name Lot No. Lot valid up to Reference standard verified by/on Valid/Not Valid Qty. Sufficient/Not Sufficient Purchase requisition raised on

Annexure–XV : Stock Solution Record

Product Name        :                                                        Name of the solution :

Stock solution No.  :                                                        Stage                         :

Test  Name             :                                                        Prepared on              :

Valid up to                 :
Preparation:                                                                      Instrument ID                       Cal. due date

Standard / Impurity Details:
Sr. No. Name of the Standard / Impurity Batch No./Lot No. Valid up to

Annexure–XVI : Primary standard vial dispensing record

Name of Primary standard:                                                                      Received date:

B.No./Lot No.:                                                                                                Valid up to:

 
Sr No. Vial no. Date of Dispensing Vial Valid up to Destroyed on Destroyed By Remarks

Annexure-XVII : Working Standard Usage Log

Date

 Name of Product/Material B. No. of Product/

Material

 Test Name

 

 Name of

Working

Standard

 B. No. of Working Standard Dispense Quantity Transfer Quantity Discard Quantity Used By Remark

Annexure-XVIII : Stock solution usage record

Sr.No

  

Date

  

Product Name

  

Batch No.

  

Test Name

  

Used By

 System Suitability Parameter System suitability recorded      by Checked by
Tailing Factor

NMT….

 Resolution

 

NLT…..

 Theoretical Plates

NLT…….

 Any other

……..

Annexure-XIX : Usage record of primary standards/GC standards/calibration standards

 Name of the standard :                                                                 Make:

Batch. No :                                                                                     Valid up to :

 

Date Used for B.No/ ID.No. Test Name Used

By

 Checked By Remarks

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