preparation, qualification and handling of reference and working standards

1.0 Purpose
1.1 To describe a procedure for Preparation, Qualification and Handling of Reference, Working and Other Analytical Standards.

2.0 Scope
2.1 This SOP is applicable for handling of reference standards, working and other analytical standards in

Quality Control laboratory at ABC Pvt. Ltd.

3.0 Responsibility
Officer QC/ Executive QC Preparation of SOP and qualification of working standards as per requirement
Assistant Manager Review of working standard qualification data, Reviewing and Training of SOP
Manager QC Final approval of working standards and Implementation of SOP
4.0 Accountability
4.1 Manager Quality Control is accountable for implementation and compliance with SOP.

5.0 Procedure
5.1 Reference standards (Pharmacopoeia)
5.1.1 Reference standard /Impurity standard for its intended purpose shall be procured from

IP/BP/E/P/USP/JP pharmacopoeia commission or Indian Foundation for Pharmaceutical

Reference Standard Substances (IFPRESS) or Promochem or through and authorized agent

of manufacture of API/ Excipient for in house material.
5.1.2 After receipt of reference standard, a reference number shall be allotted and detail shall

be recorded in a reference standard register. Relevant document pertaining to the procurement

of the reference standard like purchase order copy, copy of the invoice and delivery challan,

goods receipt note and/or certificate of reference standard, MSDS (if available) shall be

maintained in a reference standard file separately.
5.1.3 Store the reference standards in desecrator and keep the same in a refrigerator at temperature 2-8°C

(unless otherwise recommended). Maintain the vials in ‘upside’ up position.
5.1.4 Reference standard /Impurity lot shall not be used after the validity date mentioned in the

reference standard catalog or 3 years of the date of issue, if the validity is not specified.
5.1.5 After expiry keep the reference standard in a separately sealed box labeled as
“NOT FOR ANALYTICAL PURPOSE”.
5.1.6 Reference standards shall be used only for the qualification / re-qualification of working

standards. However, in case of any legal disputes the reference standards shall be used during analysis of sample during dispute.
5.1.7 Enter the details of the reference standard/impurity standard in the reference register.
5.1.8 The reference standard code and reference standard number shall be allotted as RS-Y-Z.
Where: RS-Reference Standard
Y-Stands for 3 digits number (i.e. serial number of reference std.) beginning with 001.& Z-Stands

for the 2-digit number indicate the number of times the reference standard is procured, beginning with 01
5.2 Reference standards (Non-Pharmacopoeia/ Not available with the Pharmacopoeia commission)
5.2.1 Reference standards, which are Non-Pharmacopoeia /not available with the Pharmacopoeia

commission, shall be obtained from their respective manufacturer along with the certificate of analysis.

This shall be treated as the reference standard of known purity. After receipt of this standard, a reference

number shall be allotted to them and detail shall be recorded in a reference standard register as given above.
5.2.2 This reference standard shall be used for qualification / re-qualification of working standards.

However, in case of any legal disputes the reference standards shall be used during analysis of sample during dispute.
5.2.3 Certificate of analysis received from the manufacturer along with communication and delivery

challan (if any) shall be maintained in a reference standard file separately.
5.3 Working standards
5.3.1 For preparation of working standard, select an approved batch of respective raw material and

obtain a sample of raw material as per SOP for sampling of raw material.
5.3.2 If more than two approved materials are available in warehouse, QC person shall select the

material to be used in working standard preparation with highest potency, more shelf life. Lowest

impurities, and lowest loss on drying/water of the batch to be selected
5.3.3 The quantity shall be taken as mentioned in the working standard qualification specification.
5.3.4 QC designated person shall prepare a requisition note and after getting approval from Head –QC,

the requisition shall be submit to warehouse – in charge.
5.3.5 Warehouse personnel shall dispense the approved quantity of the raw material to quality

control laboratory, on the basis of requisition.
5.3.6 If the approved raw material is not available in warehouse, QC shall demand the required

quantity of material from approved vender through purchase department and test all parameters as per specification.
5.3.7 QC analyst, other than initial analyst of raw material of that A.R. No. / Batch No., shall qualify

the working standard against respective valid reference standard.
5.3.8 To qualify the working standard, perform the Description, identification test (preferably IR),

Related Substances (RS), Assay, and water (by KF)/ loss on drying (wherever applicable).
5.3.9 To qualify the working standard, Assay and water (by KF)/ loss on drying shall be carried out in triplicate.
5.3.10 During qualification, the method should be followed as per respective material STP.
5.3.11 If the method of assay for active materials is by titrimetry then the method as per respective finish

product STP shall be followed, where finished product testing is by HPLC.
5.3.12 The RSD percentage of the triplicate analysis should comply within 2%.
5.3.13 All the individual observed values shall be within specification.
5.3.14 Working Standard shall be allotted unique identification lot number as follow: i,e WS/XXX/YY/ZZZZ
Where,
WS : Working Standard
XXX : Material code
YY : No. of qualification beginning with 01
ZZZZ : Year of qualification for example
For example prepared Cetirizine Hydrochloride working standard in the year 2026, the identification

number shall be WS/CZD/01/2026.
5.3.15 Distribute the qualified working standard into 14 equal parts in the glass vials, 12 vials shall be used

for a year. One vial shall be considered as master vial and shall be fulfill external requirement of working

standard e.g. for submission to outside /Regulatory etc. One vial shall be considered as standalone.
5.3.16 Each vial shall be used for one month only.
5.3.17 Store the vials in desecrator or box and keep the same in a refrigerator at temperature 2-8°C

(unless otherwise recommended).
5.3.18 For routine uses, take one vial of each working standard and store them in a desiccators containing

silica gel at temperature not exceeding temperature 25° C, unless otherwise specified. Seal the vial after

every use with the Para-film. After 1 month, replace the vial with a new vial and discard the previous vial

and maintain the record.
5.3.19 Enter the details of the working standard in the working standard Log Book.
5.3.20 The Working standard shall never be used after the due “Use before date” and/or expiry date.

If any change in description is observed during storage or routine usage, the same shall be discarded

and recorded.
5.3.21 Due to any unforeseen reasons like non availability of reference standards either with the

source or delay in procurement, the validity of working standard shall be extended for reasonable

period, only by Manager-QA. This shall be based on the stability studies of the product and no

significant change in the physical properties of the product
6.0 Reference
In house specification

7.0 Attachments
Annexure I : Reference / impurity standard receipt and usage log book
Annexure II : Working standard usage log book
Annexure III : Working standard vial issuance usage log book
Annexure IV : Requisition of approved material for Working standard preparation
Annexure V : Label of Working standard Vial

8.0 Distribution
Distribution of the controlled copy to concerned departments.
Additional copies may be issued for specific purpose.

9.0 Abbreviations
QA : Quality Assurance
QC : Quality Control
SOP : Standard Operating Procedure
AR : Analytical
GR : General
RSD : Relative Standard Deviation
°C : Degree Centigrade
HPLC : High Performance Liquid Chromatography
10.0 Revision History