PREPARATION, QUALIFICATION AND HANDLING OF ANALYTICAL STANDARDS

1. PURPOSE:

To lay down a procedure for Preparation, Qualification and Handling of Analytical Standards.

• SCOPE:

This SOP is applicable in Quality Control Department.

• RESPONSIBILITY:

Quality Control	:	To Prepare, follow and Review the SOP
Quality Assurance	:	To Review and check the Compliance of SOP
Head QA/Designee	:	To Approve the SOP

• DEFINITION:

Working standard: Laboratory standard, In-house standard, and secondary standard are the names of the working standard. It can be utilized for the regular analytical evaluation of active pharmaceutical ingredients or dosage forms in conditions which high purity analytical reference standard is tricky to obtain.

Reference standard:  A reference standard/ material is pharmacopoeia approved standard/ material, it is a substance prepared for use as the standard in an assay, identification, or purity test. It should have a quality appropriate to its use

• ENVIRONMENT, HEALTH AND SAFETY: Not Applicable

• PROCEDURE:

• Type of analytical standard used in Quality control department. Reference standardWorking standardPrimary standard
  • Reference standard Management :
    • Procure reference standard from the authorized source for the preparation and standardization of working  standard, write the details in the register and maintain the certificate of reference standard. 
    • Store all the reference standard in tightly containers protected from heat, air, moisture and light and keep them in properly greased desiccator containing self indicating dried silica gel at the bottom. 
    • The available status of current lot of reference standard is checked in checked from current catalogue of respected pharmacopoeia commission or through the supplier.
    • Review the status of the reference standards once in two month for USP, Ph. Eur., BP, IP and record the validity of available reference standard.
  • Handling storage and destruction of reference standard.
    • On receipt of reference standard, check the invoice, delivery note, MSDS and COA as available.
    • Executive/Designee records the receiving of reference standard.  (Reference/Impurity Standard Reciept/Usage/Destruction Record).
    • Allot a unique identification number to each reference standard at the time of receipt.
    • Allot a unique identification number to each Impurity standard at the time of receipt.
    • Maintain separate Impurity and reference standard logbook.
    • Store Reference standard at temperature between 2°C and 8°C securely, unless other specified.
    • Allow the reference standard vials to attain the room temperature and wipe outer surface of vial with tissue paper.
    • Record all consumption details in reference standards usage log(Reference/Impurity Standard Reciept/Usage/Destruction Record).
    • Whenever possible use less quantity of reference standard or impurity by altering the dilution but the final concentration of standard/impurity solution remain same.
    • For Related Compounds/Impurity standard that are not easily available so stock solution of these can be retain. This solution can be use qualitative test only i.e. solution identification, tailing, theoretical plates etc. Label the stock solution as per Annexure-4. Discard the solution if solution become hazy or system suitability criteria not achieved. Use the stock solution till the system suitability Stop the usage of reference standard once it removes from the catalogue or till its validity. If the physical properties of reference standard changes or expire or observation changes by regular use and discard the standard as per destruction procedure and record the details in Annexure-3 (reference standard usage log).
    • Retain the original label of reference standard after use or expiry of reference standard.
    • Use potency of reference standard/ impurity as given in COA/label/Catalogue if the potency is not given then use the potency of 100%.
    • Handle the reference standard and impurity standard as per instruction given in label.

Note: Do not transfer back the balance quantity (if any) to vial after weighing/usage.

• Seal the vial properly after use and store at designated place.
  • Qualification of working standards:
    • These are the substance that use as substitute for official reference standard for routine use.
    • Working standards are qualified against the current lot of reference standards.
    • Working standards are to be prepared from API/material, perform following test for qualification of working standard.

Note: Description, Identification (By IR or HPLC): Loss on drying/Water content, Assay and related substance (or any specified)

• If material is not available then procure the material from approved vendor and standardized against the reference standard.
  • In case STP and specification is not available follow pharmacopoeia method for standardization of working standard.
  • Prepare a protocol for evaluation of working standard. as per the specimen mention in (PROTOCOL FOR QUALIFICATION OF WORKING STANDARD) and approved this protocol by Head-QC.
  • Allot a unique identification number to each working standard. as: WS/AA/XXX/YY/ZZ

Where

WS       : Working standard

AA       : Current Year

XXXX : Initial four alphabet of Material

YY       : Pharmacopoeia Grade

ZZ        : number of time working standard is qualify

For example: WS/20/PARA/EP/01

• Transfer the required quantity of material for testing into the separate bag or clean container and store the remaining portion at temperature between 2°C and 8°C unless otherwise specified.
  • If the reference standard is not available then qualify the working standard against the standard provided by the manufacture of active pharmaceutical or reference standard develop by NABL certified laboratory.
  • Working standard provided by the customer can also be used for the analysis purposes. The customer provided standard shall be log.(Customer provided standard received and issue log). The same working standard number shall be use for the analysis purposes.
  • In case IP/BP standards are not available or expiry, use USP/EP reference standard for qualification of working standard.
  • In case of non pharmacopoeia working standard qualification, the analytical method use for qualification shall be validate or verify.
  • Perform the test parameter as defied in protocol.
  • Perform the Assay triplicate and duplicate injection to be injected and report the mean. The results obtain must be within specification limit. The related standard deviation of triplicate assay value should not be more than 1.0%.
  • If the assay is not within above defined criteria then the variation shall be investigate as per Incident.  
  • The method of analysis should be validate/verify method or as per respective pharmacopoeia method.
  • In case of method of analysis is by titrimetry or spectrophotometer, alternative method by HPLC can be use.
  • Calculate and report the assay/potency finally as potency on dried basis/anhydrous basis. For routine analysis, vial label shall contain. ‘as such’ potency and COA shall contain both as such and dried/anhydrous base potency.
  • Prepare the certificate of analysis for working standard.( COA FOR WORKING STANDARD)
  • If the potency is more than 100% then 100% potency shall be use.
  • Date of analysis shall be consider the initial date for calculate the validity period.
  • Allocate the shelf life of working standard based on the chemistry, validity or re-testing/expiry date provided by the manufacturer. In case the validity period of working standard shall not exceed more than 12 month.
  • Once the working standard is approved, updated the computerized list of working standard.
  • Whenever vial is issued for use, enter the details in working standard stock card.(WORKING STANDARD STOCK CARD). Maintain separate stock card for each working standard.
  • After the certification, dispense the quantity into amber colored in clean area and cap the vial immediately. Transfer the amount equal to the quantity required for one month. Label the working standard vial.
  • Prepare total 14 vials assigned for 12month or as per validity period. Each vial shall contain the quantity as per requirement i.e. 1 to 5gm in each vial. Two master vial in additional spare which contains 1 to 10 gm. Master vial shall be use in case running vial is damage/absorbed moisture/exhausted or quantity for use remain less in running vial. Quantity of working standard in vials can be reduce as per the requirement.
  • For vitamin d3 or other vitamin standard, prepare 120 vials working standard vials and fill approximately 50 mg in each. One vial use for single time analysis.
  • Store all working standard at 2°C to 8°C or other specified.
  • The validity of 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 with dry tissue paper before use.
  • Once the working standard vial validated is completed, remove it and discard as per procedure and record destruction (WORKING STANDARD STOCK CARD).  
  • Usage of working/Reference standard:
    • Before the use of working standard/reference standard, confirm the correct standard has been taken. Check the standard is with expiry date.
    • Do not uses the standard if abnormal appearance is seems and inform the section in charge.
    • Open the door of the balance and wait till the balance is stabilized, dispense the working standard as per requirement. Note the weight of standard dispense and record in working standard usage. Discard the extra working standard if it dispensed and weight the required quantity. Transfer the working standard into the volumetric flask and put the butter paper on the balance to calculate the actual transfer quantity. Write the final transfer quantity in ‘transfer quantity’ column (Working Standard Usage Record)
    • Discard quantity = dispense quantity – transfer quantity.
    • The weight should not exceed the 10% of weight to be taken.
    • Record the details in standard/reference usage record.
    • Seal the standard vial or put para-film and keep in designated place. 
    • During usage of working standard, precaution should be taken that content of vial should not contaminate to the other product or working standard or any spillage should not occur.
    • If the working standard is kept in refrigerator then keep it into desiccators for 15-30minutes to attain room temperature before use.
    • Liquid working standard to be store in ambient temperature or specified. The container/vial should be tightly closed after use. 
    • Pharmacopoeial reference standard/qualified working standard of vanillin, acetanilide, sulfanilamide and caffeine etc. shall be used for the calibration of melting point apparatus. 
  • Primary standard:
    • Procure the primary standard along with COA from the manufacturer supplier.
    • Pure grade material procure from Sigma-Aldrich, fluka, merck, spectrochem, qualigens and Rankem or specified can be used as primary standard. Primary standard shall be used without qualification. Results given in the certificate of analysis of manufactures shall be taken as potency of standard.  
    • Wherever a primary standard is received, allot an identification number as below reference.
    • CPS/XXX/YY/ZZ
    • CPS   : Certified primary standard
    • XXX : Serial number i.e. 001
    • YY   :  Current year.
    •  ZZ   :  Number of container received.
    • Label the bottle with current version of label when the bottle is received. Fill the label with received date, open by date and date of expiry. Open date is fill at the time bottle open.
    • Update the list of primary standard whenever required.
    •  The validity of primary standard shall be two year from the date of opening or expiry mention in COA.
    • Discard the primary standard after expiry.

• ABBREVIATIONS:

SOP	:	Standard testing procedure
QC	:	Quality Control
COA	:	Certificate of Analysis
WS	:	Working standard
RS	:	Reference standard

• REFERENCES:

In-house

• ANNEXURES:

   NA

1. REVISION HISTORY:

S. No.	Document No. with Version No.	Superseded Document No. with Version No.	Reference Change Control No.	Page no.	Point No./Section	Description of Change