sop for Handling of Reference Standard


sop for Handling of Reference Standard




1.1. To describe the detailed procedure for the Procurement, Storage, Usage and Destruction of Reference Standards and Impurities.

2.0. SCOPE :

2.1. This procedure is applicable for the Procurement, Storage, Usage and Destruction of Reference Standards and Impurities, being

used in Quality Control Department

3.1 Executive/Officer/Designee – Quality Control/Quality Assurance (GLP Section):
3.1.1 To ensure the proper usage of the specified Reference Standard(s)/Impurities along with documents.
3.1.2 To inform the section in-charge, in case the respective Reference Standard(s)/Impurities are not available/out of stock or

having very less quantity of the same, for the procurement of the respective Standard/Impurity.
3.2 Manager/Designee – Quality Control/Quality Assurance (GLP Section):
3.2.1 To verify and confirm the validity status of current Lot/Batch of Reference Standard(s) and Impurities.

4.1 Head/Designee – Quality Control/Quality Assurance (GLP Section):
4.1.1 To ensure the compliance of this SOP.
4.1.2 To guide and train respective users for the correct usage and storage of Reference Standards and Impurities.

5.1.1 Pharmacopoeia Reference Standard:
A Reference Standard established under the aegis of and approved by the respective Pharmacopoeia Commission / Convention (e.g. IP, BP, EP, USP etc.).
5.1.2 Chemical Reference Substance (CRS):
A substance or mixture of substances intended for use as stated in a monograph or general chapter of the respective pharmacopoeia.

CRS are Primary Standards, except for those (Notably Antibiotics) that are calibrated in International Units (IU). The latter (Antibiotics) are

secondary standards traceable to International Standards.
5.1.3 Certified Reference Material (CRM):
A reference material, accompanied by a certificate, one or more of whose property values are certified by a procedure that establishes

its traceability to an accurate realisation of the unit in which the property values are expressed.
5.2.1 Reference Standards are highly characterized specimens of drug substances, impurities, degradation products,

dietary supplements, compendial reagents, and performance calibrators.
5.2.2 Reference Standards are employed in the Identification, Purity testing and Assay of substances for Pharmaceutical

use and Pharmaceutical Preparations. They are not intended for use as drugs.

5.2.3 Reference Standard is a primary standard that has the appropriate quality within a specified context and is accepted

without requiring comparison to another substance.
5.3 Indian Pharmacopoeia Reference Standards (IPRS):
5.3.1 Indian Pharmacopoeia Reference Standards, abbreviated to IPRS, are issued/certified by the

Indian Pharmacopoeia Commission (IPC) or by the Laboratories notified by IPC.
5.4 British Pharmacopoeia Reference Standards (BPRS):
5.4.1 The British Pharmacopoeia Laboratory is responsible for the establishment and maintenance of

British Pharmacopoeia Chemical Reference Substances (BPCRS), to support the monographs of the BP.
5.4.2 The respective BPCRS can either be obtained directly from British Pharmacopoeia Commission (BPC) or

from the respective authorized agencies / bodies.
5.4.3 The current batch number (Batch No.) is always listed on the website.
5.5 European Pharmacopoeia Reference Standards (EPRS):
5.5.1 EP Reference Standards / Impurities, Information on availability and the status of current Batch / Lot Number is

provided in the Reference Standards Catalogue available from the European Directorate for the Quality of Medicines(EDQM) and its website.
5.5.2 The EP Reference Standards Catalogue is updated three times a year and is available in English only.

It includes the list of all the reference Substances currently available together with instructions for use.
5.6 United States Pharmacopoeia Reference Standards (USPRS):
5.6.1 USP Reference Standards / Impurities, Information on availability and the status of current Batch / Lot Number is

provided in the Reference Standards Catalogue and its website.
5.7.1 After the receipt of information of launching of a new product or existing lot of standard is expired

(Validity period over) or a new lot has been issued / released, by the respective pharmacopoeia commission / convention,

procurement procedure for the respective standards/impurities shall be initiated by Head/Designee-QC after taking the approval of Plant head.
5.7.2 Reference standard/Impurity is/are required and to be procured/arranged for the analytical purpose under the following situations:
a. The Product is Pharmacopoeial and the Pharmacopoeial Reference Standard/Impurity is available.
b. The Product is Pharmacopoeial and the Pharmacopoeial Reference Standard/Impurity is not available.
c. The Product is Non-Pharmacopoeial and the Pharmacopoeial Reference Standard/Impurity is available.
d. The Product is Non-Pharmacopoeial and the Pharmacopoeial Reference Standard/Impurity is not available.
5.7.3 In case of the situations `a’ and `c’, the Head/Designee–QC, shall raise the indent and arrange for the

Pharmacopoeial Reference Standards and Impurities.
5.7.4 Reference standards shall not be used after validity date mentioned in the catalogue or shall be used upto

three months after date of issuance of next lot (if validity period is not specified) or as per the respective specified

validity period, in case of the situations `b’ and `d’.
5.7.5 Status of the Pharmacopoeial Reference Standard / Impurity shall be checked by Executive/Officer/Designee-GLP

on regular basis, against the respective Catalogue(s)/Internet Website for the status of current Lot/Batch No., if validity

period is specified on website than the same shall be updated as per format in Annex-I.
5.7.6 In case of the situations `b’ and `d’, as mentioned above; the reference standards/impurities shall be arranged/ received

from the R&D centre of Troikaa Pharmaceuticals, Authentic chemical manufacturers (e.g. Fluka, Merck, Lancaster, Sigma Aldrich, JT Baker, Rankem etc)

, other agencies/bodies duly authorized by different competent authorities or can be arranged from the respective

approved vendor/supplier. Certificate of analysis for the same (if applicable) shall be available in the QC department.
5.7.7 All the standards/Impurities, received from authentic/authorized/certified/recognized sources, Pharmacopoeial agencies,

Troikaa R&D Centre and approved vendors, shall be considered as Primary Standard/Impurity.
5.7.8 On receipt, the Reference Standard/Impurity Vial/Container shall be checked for following attributes (But not limited to):
Integrity of the Vial / Container.
Pharmacopoeial Status.
Label of the respective Vial / Container.
Name of Reference Standard / Impurity.
Cat No. / Lot No. / Batch No. of Reference Standard / Impurity.
Availability of respective COA , MSDS etc.
Any other information like potency, instruction of usage of material and its storage, etc.
Receipt record of all Reference standard(s)/Impurities, such as Source, Lot No., Date of receipt, Received by, Quantity received, etc.

shall be maintained as per Annex-II, and same shall be updated as and when applicable by Executive/Officer/Designee-GLP.

5.8.1 The official and authorized uses of Reference Standards are specified in the respective monographs and

general chapters, and they include (But Not Limited to): Use in Quantitative analysis such as Assays for Drug Substances and Formulations (Drug Products), Limit Tests,

Preparation of working standard, etc. Use in Qualitative analysis such as Identification tests, System Suitability Tests, etc. Use as Performance Standards and Calibrators, such as Dissolution Calibrators, Melting Point Standards, Verification of Particle count, etc.
5.8.2 Reference Standards do not carry an expiration date as long as they are in distribution. A lot of any RS may be used as long as

it is listed as “Current Lot” in the current (most recent) official Reference Standards Catalogue (website).
5.8.3 Users are responsible to ensure that the Reference Standards/Impurities they are using have official status either as a “Current lot”

or as a “Previous lot” within the valid use date. Same can be verified by referring the information available as per Annex-I.
5.8.4 Directions for usage are available on the label of each Reference Standard. These are lot-specific. The label includes safety

warnings, required information for controlled substances, and calculation values for standards with quantitative applications.
5.8.5 As and when required, an appropriate quantity of the Reference standard shall be used for the qualification of

Secondary Standard (Working Standard) and for analysis of product /materials in case working standard is not available.
5.8.6 Potency mentioned on the label or COA (Certificate of Analysis- In case of CRS/CRM) shall be used for calculation.

If potency is not mentioned on label or COA, 100.0 % Potency (on as is basis) shall be considered for all calculations.
5.8.7 After every use, consumption record of quantity of the respective Standard / Impurity shall be maintained as per the format mentioned in Annex.
5.8.8 The quantity of the respective Reference standard / Impurity to be used for a particular test can be reduced as per the quantity

available in the respective vial / Container. While doing so, prior approval shall be taken from the Head/Designee-QC, and

the final concentration of the solution shall remain unchanged.
5.8.9 Where a Reference Standard is required to be dried at specific temperature before being used; dry only

appropriate quantity of material and not the original vial / container.
5.8.10 If the quantity received/remaining of a particular standard/impurity is less for qualitative use, then the dilution

(The Stock Solution) being prepared can be stored and used till all the respective System Suitability parameters are

met as per the specified criteria and no other extra peak(s) [Interfering with the respective analysis] are observed during the analysis.
5.8.11 All such stock solutions shall be given a Unique Identification Number, as mentioned below:
RSS : Stands for Reference Stock Solution.
XX : Stands for the Unique Identification Number, starting from 01 for the current year.
YY : Stands for the last two digits of the current year.
5.8.12 All such solutions shall be used for qualitative purpose only (Identification test, System suitability, etc) and not for the quantitation purpose.
5.8.13 All such solutions must be stored in refrigerator, and labeled as mentioned below:



Name of the Standard / Impurity Stock Solution
Reference Stock Solution Number
Batch / Lot Number of Standard / Impurity
Pharmacopoeial Status
Prepared For (Material/Product Name and AR No.)
Prepared By (Sign / Date)
Spec. / MOA /STP Number
    Checked / Verified By (Sign / Date)

5.8.14 Reference Standards and Impurities shall be accurately weighed, taking into account the relatively large errors associated with weighing of small quantities.
5.9.1 After usage, all reference standard / impurity vials /containers shall be closed properly (with rubber stopper and aluminum seal)

and stored at their specified place and under specified conditions.
5.9.2 Each reference standard shall be preserved in their original vials/containers under lock and key.
5.9.3 Extra care/precautions shall be taken while handling any Hygroscopic/Photosensitive Reference standards/ Impurities.
5.10.1 Reference standard/impurity shall be destroyed as per the following conditions (But not limited to) and record shall be maintained as per format in Annex-I: After the expiration (Validity Over) of existing Lot/ Batch No. Existing Batch / Lot No. gets decomposed / contaminated.

5.11.1 For usage, always transfer only the required quantity from the respective vial / container.
5.11.2 Never transfer the remaining quantity of the standard back to the original vial / container.
5.11.3 If the respective Standard is stored at 2 – 8 °C, never use it for analysis immediately after taking it out from the refrigerator.

Allow it to attain the ambient temperature, and then use.
5.11.4 Never insert any external device, such as spatula, glass rods, butter paper, etc into the vials, as it may contaminate the standards.

Sr. No. Abbreviation used Full form of abbreviation used
1. QA            Quality Assurance
2. QC            Quality Control
3. AGM          Assistant General Manager
4. IP              Indian Pharmacopoeia
5. BP            British Pharmacopoeia
6. EP            European Pharmacopoeia
7. USP         United States Pharmacopoeia
8. GLP          Good Laboratory Practices
9. MSDS        Material Safety Data Sheet
10. COA         Certificate of Analysis

Annex – I : Reference Standards / Impurities: Receipt, Verification and Destruction Record.
Annex- II : Usage Record of Reference Standard / Impurity.


Sr. No. Reference Title Author Name Edition Page No.

SOP for testing of ETP water

sop for Calibration and Maintenance of Laboratory Instruments and Equipment

Disposal of Residual Sample or Left Over Material

sop for for Laboratory Incident

standard operating procedure temperature monitoring

sop for drying of silica gel

sop for operation of infrared moisture balance

sop for preparation of mobile phase

sop for treated RO water

sop for Preparation and Issuance of Analysis protocol standard

sop of placebo and impurity stock solutions

sop for disposal of residual sample  

sop for handling of pharmacopoeial changes

sop for procedure for operation of ultrasonic cleaner

difference between UPLC and HPLC

sop for for Emergency Eyewash and Shower

sop for operation and calibration of total organic carbon analyzers

sop for operation of cobb tester

sop for Operation and calibration of atomic absorption spectrophotometer

sop for Operation and calibration of gas liquid chromatograph

sop for operation of humidity oven

sop for operation and calibration of serological water bath

sop for monitoring of drain trap

sop for destruction of analytical samples after testing and control samples

sop for destruction of used chemicals

Sop for Operation of suction pump

sop for Operation and calibration uv cabinet

sop for Operation and calibration of bulk density apparatus

sop for operation and calibration of shore hardness tester

sop for operation of rub proofness tester

sop for monitoring of purified water

sop for Retesting of packaging materials

sop for Retesting and resampling of raw materials

sop for Control of issuance of record of analysis green sheets

sop for Control of computer passwords

sop for sampling of packaging materials PM

sop for sampling of sterile raw material

sop for sampling of intermediates and finished products

sop for operation and calibration of friability test apparatus

sop for approval and rejection of packaging materials

sop for non conformance of RM PM and finished product

sop for collection storage and disposal of control samples

sop for trend analysis of finished products

sop for Chromatographic practices and system suitability

SOP For Good Laboratory Practices

sop for cleaning and operation of sieve shaker

general specification of packing material cartons

sop for Password for Analytical Instrument and LIMS software

sop for Rounding off numerical analytical results

sop for sampling of bulk and finished product

sop for cleaning of spillage material

sop for Handling of Reference Standard

sop for hplc column maintenance and washing

procedure for sampling and handling of bulk sample

STP for borewell generation point (raw water storage tank)

sop for preparation and standardization of 0.1M Zinc Sulphate

Operation &calibration of analytical balance (dhona)

Operation and Calibration Procedure for Disintegration Test apparatus

sop for preparation and standardization of 1 M Hydrochloric Acid

Preparation and standardization of 0.1 M ceric ammonium sulphate solution

sop for preparation and standardization of 0.05 m iodine solution

validation of volumetric solution 0.1m ammonium thiocyanate

handling of reference standard and preparation of working standard

sop for water sampling and analysis

sop for operation for validation of excel worksheets

sop for laboratory cleaning

sop for stability of volumetric solutions

sop for preparation of raw material in process finish product packing material data sheets

sop for handling of hazardous chemicals

sop for handling of glassware and allocation of identification number

sop for operation cleaning and calibration of bursting strength tester

sop for rounding off the analytical test results

procedure for Analyst Qualification

sop for operation and calibration of dissolution Apparatus

procedure for maintenance of desiccators

sop for for hplc column receipt checking id no and regeneration

safety data sheet for laboratory chemicals

procedure for handling of poisonous chemicals

sop for cleaning of sampling devices

sop for calibration procedure of instruments

sop for specification and standard testing raw material packing material and finished product

procedure for operation and calibration of potentiometric titrator

procedure for operating and calibration of digital hardness tester

procedure for disposal of expired chemicals, reagents and solvents

sop for behavior in quality control department

sop for preparation and standardization 0.1M sodium thiosulphate

sop for preparation and standardization 0.1M Disodium Edetate

preparation and standardization 0.1M Sodium Hydroxide Solution

Preparation and standardization of 0.1M Perchloric acid solution

sop for preparation 0.05M edetate disodium

sop for preparation 0.1M silver nitrate

sop for Operation and Calibration of High Performance Liquid Chromatography

sop for UV & Visible Spectrophotometer

procedure for Cleaning of laboratory glassware

Cleaning of Instrument, Instrument bench and surrounding area of Quality

Safety Precaution in Quality Control Department

Operation & Calibration of Analytical Balance

Calibration of Glassware in Quality Control Department

handling of samples received in Quality Control

Cleaning and Operation of Refrigerator

Operation, Cleaning and Calibration of water bath

Operation & Calibration of Refractometer

Operation and Cleaning of Centrifuge Apparatus

cleaning, operation & calibration of Vernier caliper

Calibration of Fourier Transform Infrared Spectrophotometer (FTIR)

Cleaning and operation of Moisture Analyzer

Cleaning & Operation of Vacuum pump in Quality Control Department

Operation and Calibration of Polarimeter

Cleaning and operation of Magnetic Stirrer

Cleaning Operation and Calibration of Melting Point

Operation Cleaning and Calibration of Muffle Furnance in Quality Control Department

procedure of operation and Cleaning of Sonicator

Operation Cleaning & Calibration of pH meter in Quality Control Department

Entry and Exit in Quality Control Department


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