SOP for Reference Standard Control

OBJECTIVE

To provide a procedure for controlling and storage of reference standards.

SCOPE

This procedure shall apply to all the reference standards that are used for analysis.

RESPONSIBILITY

• It is the responsibility of the QC Executives to ensure that the standards are used appropriately, and stored in the right conditions.
• It is the responsibility of the QC Manager to ensure that all standards are prepared & qualified against reference standards & documented.

PROCEDURE

Classification of Reference Standard

1. Primary Standards: These have been prepared and classified as such by competent accredited bodies such as USP, BP, FDA, and WHO. Unless otherwise stated primary standards are taken as being 100% pure.
2. Secondary Standards: This is prepared from a selected batch of an active ingredient after it has been tested against a Primary Standard and has passed all monograph requirements.

ALSO READ: Use of In-house Reference Standards Beyond Pharmacopoeial Standards

Classification of Secondary Reference Standards

Selection of Sample, Sample quantity & sampling of Raw material

• Select the latest approved batch of Raw material preferably having maximum assay.
• The sampling quantity shall be calculated based on the sample required for analysis and preparation of secondary reference standards.
• Perform the sampling as per the current SOP of sampling of secondary reference standard

Analysis of material:

• Carry out the following test for the preparation of the secondary reference standard

1. Assay *
2. Loss on drying/Water content
3. I.R. (Where applicable)

* Assay shall be done in Triplicate

• Enter the results in the datasheet for secondary reference standards of the respective material. A secondary reference standard data sheet shall be prepared as per Attachment-I
• Calculate the average of three assay values obtained on as-is basis.
• The RSD of three assay values obtained on as-is basis should not be more than 1.0% for chemical assay and 5.0% for microbial assay.
• When approved the following should be entered on the Certificate of Analysis for Secondary Standards:

1. Name of Secondary standard.
2. Date of certification.
3. Expiry date.
4. Assay (as such).
5. Loss on drying/ Water content
6. Analyst’s signature and date.
7. Approval signature and date.

Preparation & labeling of vials

• Prepare the List of secondary reference standards as per Attachment-II (List of Secondary reference standards). Assign the reference number to the Secondary Reference Standard as follows. Number the Secondary Reference Standard as

SRS/XXX-YY/BB

Where,

SRS: Secondary Reference Standard,

XXX: Corresponds to the serial no starting from 001.

YY: Corresponds to the last two digits of the year in which SRS prepared.

BB: Corresponds to the no. of vial prepared for particular SRS starting from 01.

e.g: SRS/001/24-01,

Where

SRS – Secondary Reference Standard,

001 is the reference no for – Ibuprofen,

20 describes the secondary reference standard prepared in the year 2024,

01 is – First secondary reference standard in the series in the year 2024.

The second secondary reference standard of Ibuprofen prepared in the year 2024 shall be numbered as SRS/001/24-02.

ALSO READ: Difference between Assay and Purity

• Store the material in light-resistant glass vials closed with a cap.
• Label the vials with the following details.

1. Name of Secondary Reference standard
2. Ref. No.
3. Assay (On as such basis)
4. LOD/Water content
5. Date of preparation
6. Use before

• Assign one-year shelf life for secondary reference standard when the expiry of the sample used for secondary reference standard preparation is more than one year
• If the secondary reference standard is not qualified in-house and is supplied by an external party, the results from the certificate of analysis shall be adopted and recorded on the secondary reference standard analytical report. A reference standard number is assigned to a such reference standard and recorded.

Storage and handling of reference standards

• Store all secondary reference standards in the A.C. control area (below 27°C)/ refrigerator (Between 2 to 8°C). Keep the vials air tight and protected from heat, moisture, and light. Primary Standards should be stored in their original stoppered containers.
• Moisture-sensitive Reference Standards must be stored in desiccators.
• Unless otherwise directed, Reference Standard must be dried before use as directed in their labeling or in the monograph.
• Reference Standards will be used in the assay of certain raw material or finished dosage forms, or to determine a specific impurity in either.

Precaution

• The analyst shall check the expiry of the secondary reference standard before use.
• The analyst shall keep the standard out of the recommended storage for as short as possible to protect it from light and moisture.
• Equilibrate secondary reference standards to room temperature before use, which are stored in the refrigerator.
• Use the required quantity and do not put back the secondary reference standard in the vial.
• Ensure proper closing of the vial after use.

ABBREVIATION

QC: Quality Control

QA: Quality Assurance

SRS: Secondary Reference Standard

ANNEXURE

Nil

REVISION HISTORY

Nil

ALSO READ: SOP for Preparation of Data Sheets for Working Standard