sop for Handling of Reference Standard

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sop for Handling of Reference Standard

1.0. OBJECTIVE :

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

3.0 RESPONSIBILITY :
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.

4.0 ACCOUNTABILITY :
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.

5.0 PROCEDURE :
5.1 DEFINITIONS:
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 REFERENCE STANDARDS:
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 PROCUREMENT OF REFERENCE STANDARDS AND IMPURITIES:
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 USAGE OF REFERENCE STANDARDS / IMPURITIES:
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):
5.8.1.1 Use in Quantitative analysis such as Assays for Drug Substances and Formulations (Drug Products), Limit Tests,

Preparation of working standard, etc.
5.8.1.2 Use in Qualitative analysis such as Identification tests, System Suitability Tests, etc.
5.8.1.3 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/XX/YY’
Where,
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:

QUALITY CONTROL DEPARTMENT
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 STORAGE OF REFERENCE STANDARDS / IMPURITIES:
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 DESTRUCTION:
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:
5.10.1.1 After the expiration (Validity Over) of existing Lot/ Batch No.
5.10.1.2 Existing Batch / Lot No. gets decomposed / contaminated.
5.11 PRECAUTIONS:

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.

6.0 ABBREVIATION :
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

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

8.0 REFERENCE :