SOP: Handling of Working Standards

ABBREVIATIONS AND DEFINITIONS 

• COA : Certificate of Analysis
• HPLC : High Performance Liquid Chromatography
• INN : International Nonproprietary Name
• IR  : Infrared
• QC : Quality Control
• QA : Quality Assurance
• QO : Quality Operations
• Qty. : Quantity
• SCM : Supply Chain Management
• UV : Ultraviolet
• WS : Working Standard

Primary Chemical Reference Substance: A designated primary chemical reference substance is one that is widely acknowledged to have the appropriate qualities within a specified context, and whose assigned content when used as an assay standard is accepted without requiring comparison with another chemical substance.

Reference Standard: Chemical substance whose potencies are known and used as reference sample in UV, lR and chromatographic procedures.

Working Standard: A chemical substance that is standardized against reference standard and used as control material during analysis.

Expiry dates: Date put on the label of container beyond longer be used for analysis purpose.

PRECAUTIONS

1. Immediately recap the container containing working standard after use.

2. Keep the working standard alphabetically in its designated places as per storage condition.

3. Use clean dry spatula during sampling, vial preparation and use.

4. Check the expiry date of a working standard before use.

5. Use reference standard from valid lot to standardize a material.

6. CRS can be used instead of WS, if WS is not available in QC laboratory. (Maintain Standard Concentration)

PROCEDURE

1. Selection of Material

1.1. Officer to Sr. Executive will select latest batch of active raw materials for WS preparation considering the following: 

• Quality control recent passed material.
• Officer to Sr. Executive will received from approved vendor with Manufacturer's Certificate of analysis (COA).
• WS expiry date must not exceed the material manufacturer’s expiry date/retest date.
• Analytical results obtained during analysis of the material must comply with the entire test parameters of the specification.
• Officer to Sr. Executive will select the material of higher purity among the passed batches.
• Officer to Sr. Executive will collect Certificate of analysis (COA) and test procedure from the supplier if the material is not included in the pharmacopoeia i.e. INN materials.

2. Collection of Material

2.1. Officer to Sr. Executive will give requisition for the sufficient quantity of raw material from the selected passed batch to warehouse. The required quantity shall be based on one year consumption including buffer stock.

2.2. If the raw material is not available in Warehouse, then Officer to Sr. Executive will place requirement to SCM or other respective department to collect the working standard or raw material for working standard preparation.

2.3. Sampler (Raw Material) will perform the sampling using clean dry sampling utensils and affix the sample label on the sampling poly bag/ container. Fill up the label manually.

2.4. Sampler (Raw Material) will give entry in the weight register of the sampling booth.

3. Standardization.

3.1. If the assay method of the sample is in HPLC/UV/Bio-Assay reader then Officer to Sr. Executive will take the required quantity of sample to run the assay test against respective primary chemical reference substance to determine the potency. For INN material standardize for assay against INN reference standard or Compendial reference standard (Which are applicable).

3.2. lf the assay method of the sample is in Potentiometric titration/only specific absorbance value used for the determination of assay (i.e., no standard required) then Officer to Sr. Executive will compare the identification test with the respective reference standard.

3.3. Officer to Sr. Executive will collect following test results: (i) Appearance, (ii) Identification, (iii) LOD/ Water content, (iv) Related Substances, and (v) Assay (If it is done against reference standard) from Raw material test report sheet if the working standard is prepared within one month from the release date of the material.

But if the working standard is prepared after one month from the release date of the material, perform the analysis of following parameters: (i) Appearance, (ii) LOD/ Water content, and (iii) Assay, and capture the results of other test parameters (Identification and Related Substance) from Raw material test report sheet.

3.4. For the raw material received from vendors, Officer to Sr. Executive will perform complete testing of the material before the material is used for qualification as working standard and the same test result shall be captured in the Certificate of Analysis of working standard.

3.5. Officer to Sr. Executive will compile details of the test & record the data on working standard logbook and take approval for the Certificate of analysis for working standard from Sectional Head or his nominee.

3.6. Before expiry of any chemical reference substance, prepare additional stock (If considerable) working standard to ensure additional stock of working standard with extension of use of this to utilize the CRS in maximum cases. Prepare vial quantity and assign individual vial’s “use before date” as per requirement and also issue it after expiry of the current lot of working standard.

4. Vial Preparation and labeling

4.1. Officer to Sr. Executive will pour sufficient quantity of materials (for both hygroscopic and non-hygroscopic) sample separately into 15 airtight amber glass containers where first 12/13 vials will be used for 12 months (1 vial for 1 month) QC analysis & rest of the vials will be used as a buffer quantity or for Regulatory Affairs purpose or other purpose & issue the working standard one after another lot.

4.2. Officer to Sr. Executive will Prepare one vial for Travoprost for which batch production is very limited and the WS vial will open very few times throughout the year.

4.3. Officer to Sr. Executive will give one year expiration date for Travoprost which stability was proved by a shelf-life study.

4.4. Officer to Sr. Executive will label the in-house working standard with the following information

• Name 
• Batch No.  
• Potency
• LOD/Water content
• Vial No. (Vial number format will be xx/yy, where xx is the number of vial and yy is the total number of vials. For example, if 15 vials are prepared, the number for first and second vial will be 01/15 and 02/15 respectively).       
• Preparation Date
• To be issued on
• Use Before
• Storage Condition
• Prepared By
• Quantity: {Write down the quantity of the material and affix the weight in working standard preparation logbook.

4.5. Officer to Sr. Executive will label the working standard received from supplier or dossier submission and other purpose of the plant with the following information:

• Name
• Batch No.
• Potency
• Issue date
• Expiry Date
• Storage Condition
• Quantity

4.6. Officer to Sr. Executive will prepare list of hygroscopic materials. For the hygroscopic materials, Officer to Sr. Executive will determine the Water/LOD content to calculate the strength on as is basis before each use.

5. Assigning Expiry Date:

5.1. Officer to Sr. Executive will assign the expiry date of the working standard as one year from the date of release of Raw material if the working standard is prepared within one month from the date of release. If the working standard is prepared after one month from the release date of the material, then assign expiry date as one year from the standardization date. If any non-conformance or incidents happened during the qualification of working standard, that should be investigated and CAPA should be taken accordingly.

5.2. Officer to Sr. Executive will consider that the Working standard expiry dates should not exceed expiry date/retest date of the material declared by the manufacturer.

5.3. Officer to Sr. Executive will issue WS vial and issued vial should be used month wise (vial issue and last use date in the same month) i.e. If a Working Standard vial issued at 01 January 2020, it can be used up to 31 January 2020, similarly if a Working Standard issued at 11 April of 2020, it can be used up to 30 April 2020. If a WS prepared on any date of a month, the initial vial will be valid till the last date of the month, for example, a WS prepared on 20 January 2020, the first vial will be valid till 31 January 2020 and for the last vial (12th//13th vial), expiry will be assigned date equivalent to 1 year from the release date or working standard analysis date of the material. If the material expiry is below 1 year, then prepare the vial up to the expiry month including buffer quantity. For example: If the WS has a shelf life of three months, prepare 4 or 5 vials as per requirement.

5.4. Officer to Sr. Executive will discard previously issued vial at the first day of every month and a fresh vial shall be issued for use. If the first day of respective month is a holiday, then the previously issued vial shall be discarded and a fresh vial shall be issued for use on the first working day after holiday.

5.5. Officer to Sr. Executive will keep the disposal record on working standard register and input their reconciliation status for working standard.

6. Storage condition:

6.1. Officer to Sr. Executive will store the working standard container as per storage condition.

6.2. Officer to Sr. Executive will each opened vial shall be maintained according to its storage condition, i.e. if storage condition is below/ not more than 25°C then keep in the desiccators under room temperature (15°C to 25°C) and if the storage condition is 2-8°C then keep in the refrigerator where 2-8°C temperature is maintained and if the storage condition is -20°C then keep in the freezer where -10°C to-25°C temperature is maintained. If nothing is mentioned as a storage condition then find storage condition from the MSDS or from Vendor/ Suppliers support and maintain the respective storage condition.

7. Use & Dispose of working standard

7.1. Officer to Sr. Executive will check the expiry date of a working standard before use.

7.2. Officer to Sr. Executive will take the working standard from the desiccators/refrigerator/ freezer.

7.3. Officer to Sr. Executive will keep it few minutes and follow the SOP of Handling of Desiccators to attain room temperature if taken out from refrigerator/freezer.

7.4. Officer to Sr. Executive will weigh quickly with minimum exposure to air.

Officer to Sr. Executive will close the container tightly and wrap the cap with para film & keep it in the right place.

7.5. Officer to Sr. Executive will input the reconciliation status on working standard logbook.

7.6.Officer to Sr. Executive will dispose the working standard vial and material following the SOP Laboratory Waste Disposal.

List of working standards

Officer to Sr. Executive will yearly plan should be prepared for In-house Working Standard as per Appendix-H. Whenever the new working standard requirement generated, it shall be incorporated in the existing Yearly planner as an annexure. Prepare monthly list of working standards for In-house and Supplier following Appendix-E and Appendix-F within the first week of every month. In-house Working Standard preparation shall be completed before the expiry or as when required.

Officer to Sr. Executive will not receive any working standard from the supplier without Certificate of Analysis (COA). Prepare document (following Appendix-B) during issuing of the respective working standard mentioning name of the standard, supplier name, batch no., potency, issue date, expiry date, and storage condition achieved from corresponding manufacturer's COA.

Officer to Sr. Executive will archive all standardization documents for 5 years after the expiry of working standard.

REFERENCES

• British Pharmacopoeia
• United States Pharmacopoeia
• European Pharmacopoeia
• World Health Organization (WHO)