SOP for Handling of Reference Standards
This Document describes (Standard Operating procedure) SOP for Handling of Reference Standards and Preparation of working standard
SOP for Handling of Reference Standards and Preparation of working standard
I: Objective and Scope
The purpose of this SOP is to lay down a procedure for handling of Reference Standards and Preparation of working standards.
This procedure is applicable for handling of Reference Standards and Preparation of Working Standards in Quality control.
II: Responsibility :
Quality Control Trainee/ Officer / Executive / Designee:
- To handle the reference standards & impurity standards as per standard operating procedure.
- To prepare working standard as per standard operating procedure.
- To report any non conformance, deviation, OOS occurred during follow of this SOP
- To maintain the document related to handling of reference standards and preparation of working standard.
Quality Control Head/ Designee:
- To give requirement of reference standards/ impurity standard to Purchase.
- To ensure the overall compliance of SOP.
III: Introduction and Procedure :
Definitions :
- Reference standards: A substance that is widely acknowledged to have the appropriate characteristics within a specified content and whose value accepted without requiring comparison to another substance and supplied by a compendia authority (such as USP, EP, BP or IP committee) or authorized agencies.
- Working standards: A substance of established quality and purity, as shown by comparison to a reference standards, used as a reference for routine laboratory analysis.
Procurement of Reference and Impurity standard:
- The requirement of reference standards and Impurity standard shall be given to purchase department by Head QC or designee.
- Purchase order shall be raised by purchase department for the desired “Reference Standard” from authorized agency.
- The purchase order shall specify the name and source of reference standards and shall be authorized by Head Operation or CEO.
- New Reference/Impurity standard shall be procured in case of existing reference standard shall get exhausted or if the (regulatory) authorities change the current Batch No. / Lot No. of the reference standards.
- Store all Reference standards / impurity standards as per the storage condition mentioned in respective MSDS from supplier.
- Reference substances or Reference standards are authentic purified chemicals or substances supplied by the official pharmacopoeia commissions. These are used for comparison for determining the purity of the test specimen.
- In case reference standard is not available in any of the pharmacopoeia catalog, manufacturer shall be requested for their reference standards/ working standards with certificate of analysis.
- As Reference Standards are available only in small quantities, working standards are prepared to act as substitutes. These are prepared from approved raw material and validated against authentic Reference standards or Reference substances. Standardizations records of Working Standards are maintained in the QC laboratory.
- If reference standards are not available, then working standard from manufacturer with COA shall be arranged and used for routine analysis.
Procedure for receipt and storage of Reference standard/Impurity standard :
- Reference standards shall be received in the original container of the certifying and supplying agency.
- If any discrepancy observed in reference standards; immediately inform to department head to take further actions.
- The Lot number/Batch number and validity of reference standards shall be verified on official website of USP/BP/EP/IP.
- The Certificate of Analysis, batch validity statement (If applicable) shall be downloaded from official website of USP/BP/EP/IP.
- For USP reference standard go to website usp.org
- For EP reference standard go to website edqm.eu
- For BP reference standard go to website pharmacopoeia.com
- After verifying all the details of reference standards, entry shall be made in “Reference Standard Register” refer Annexure I.
- Reference standards and Impurity standard must be stored in its original stopper container.
- All reference standards shall be stored in an airtight pack with a desiccant in a refrigerator between 2°C to 8°C; or according to the specific instructions given on the label.
Validity of Reference standards/Impurity Standard:
- Validity of Official reference standards/Impurity standards shall be verified on official website of USP/BP/Ph. Eur. in first week of every month.
- Official website ID are mentioned above
- Record shall be maintain as per Annexure VIII
- If any reference standards/impurity standards will be expire in next 3 month then requirement shall be given to Purchase department to procure new reference standard/impurity standard.
Handling of Reference standards :
- Where drying is recommended, a small quantity shall be transferred to a clean dry container for drying and the original container shall not be dried as such temperature before weighing. Takeout the reference standards bottle and keep in desiccators and allow it to equilibrate with room temperature. Material taken out for weighing that is an excess of the requirement should not be returned to the container of the standards hence very small amount must be removed at a time.
- The consumption record of the reference standards shall be maintained refer Annexure II.
Preparation of working standard:
- Working Standard shall be always standardized/ qualified against Reference Standards.
- If a reference standards is not available then working standard shall be standardized against standards received from authentic sources or manufacturers having the manufacturer’s certificate of analysis with characterization data. The manufacturer COA shall give reference of reference standards they have used.
- Select an approved batch of high purity of respective material and collect the required amount of sample for working standard qualification.
- If approved batch is not available and new raw material is received then perform complete testing as well as additional tests as per mentioned in point number Working standard qualification shall be done.
- The new raw material is complies with all specification criteria then after approval of new raw material working standard shall be effective.
- Assay and Loss on drying /Water content tests shall be carried out in triplicate (three samples preparation).
- Related substances/ Organic impurities test shall be carried out as per respective standard test procedure.
- Perform the appearance, identification, water content/Loss on drying, and assay / potency in triplicate, as per relevant procedure/ Pharmacopoeial methods and record the observations and results on the respective analytical protocol.
- Consider the average of assay (on as is basis) values for the assay / purity, provided the RSD of three values is not more than 1.0 %.
- On completion of qualification Certificate of analysis of respective working Standard shall be prepared as per Annexure VII.
- Sub divide the material into equal quantity and transfer to 4 + 2 or as per requirement clear/amber color glass bottles/vials and store in a refrigerator / desiccators, as applicable, away from heat, light and moisture after labeling.
- In case of desiccators, keep it over a silica gel that has been previously activated at 105°C± 2°C.
- Weigh accurately 2 g or as per requirement of the material (i.e. Maximum 5g) and fill in each vial. Affix the label on Individual vial as per Annexure-VI.
- Weight of working standard (Filled quantity) shall be mentioned for each vial in working standard issuance and destruction record i.e. Annexure V.
Note I: Extra vials are prepared to cater the requisition from Regulatory agencies/ any other customer or in-house use if in case vial exhaust in between or spoiled due to improper handling.
Note II: More than 4 vials can also be prepared if the consumption of a working standard is more.
- Store the material in amber color glass vials closed with rubber bungs and sealed with aluminum seal.
- During filling of the working standard into the vial follow safety precautions as well as care must be taken to avoid any contamination.
- Put the Clause “Use within 90 days after opening” as applicable. Give the Validity not more than one year or Expiry date (as DD/MM/YY) from the date of preparation. Store the filled vials in a desiccators/rack provide/recommended storage. Enter the details of usage of working in Annexure IV.
- Affix a Label to all bottles of Working Standards with details:
Name of Working Standard
Working standard No.
Prepared by
Valid from
Use before
Opened on
Potency
LOD/Water
Vial No.
Validity up to
Use before
- Working Standard qualified by manufacturer of material can be used if supplied with COA.
- All the above information shall be checked and verified by Head QC. The filled label shall be affixed on the Qualification record of working standard.
- Prepare a list of working standard to identify the due date for preparation of working standard as per Annexure-III
- In case of absence of API or CRS (BP/EP/USP) working standards received from manufacturer shall be used for respective analysis.
- Before use of the working standard, follow the instructions (if any) given on the label of the working standard.
Handling and storage of working standard:
- On preparation/receipt of working standard affix the label as per annex VI and issue the vial as per requirement for usage. The validity of the issued vial is three months from the date of issuance. The issuance log for the standard vials shall be maintained.
- On issuance of the fresh vial of working standard the left over quantity of working standard in previous vial shall be destroyed.
- In case of vial broken during handling or quantity exhausted; next vial shall be issued and record shall be maintain in Annexure IV &Annexure V.
- Analyst has to ensure the validity of the vial before starting the analysis and seal the vial with aluminum seal after every use.
- Vials which are in current use and to be stored at ambient condition shall be stored in a desiccators containing self-indicating silica gel.
- Self-indicating silica gel can be used up to one year. If the color of Silica gel is changed from blue to white, it shall be dried at 105°C, till the color of silica gel becomes blue.
- The remaining sealed vial of each WS shall be stored in black or plain colored double polybag indicating identity of WS. These vials shall be stored in a cool and dark place or as per the recommended storage condition.
- If a working standard is stored under the condition other than the ambient, allow the container to equilibrate to room temperature before weighing.
- Do not insert any of the dispensing equipment like spatulas, glass rods, and butter paper in to the working standard containers.
- Excess material after weighing shall not be returned to the container of working standard.
- The new working standard shall be prepared before the validity of existing working standard in case it gets exhausted or spoiled or because of mishandling.
- The vials remaining after the validity date of respective working standards shall be destroyed.
Note:
- The working standard shall not be re-validated after completion of validity date under any circumstances.
- The consumption record of the working standard shall be maintained refer Annexure IV.
Disposal of working standard :
- Expired working Standards / Reference standards should not be used and should be disposed immediately.
- The destruction record of the working standard shall be maintained refer Annexure V.
Numbering system for working standard:
- All the working standards shall be numbered as per the following numbering system.
- Example: Assign the working std. no. as : X AAAAA BBCC
Where,
X: – stands for standard
AAAAA: – represents material name (Five alphabets of material name)
BB: – represents year of preparation
CC: – represent the number of working standard preparation during the year.
Frequency: Yearly and as and when required
Annexure -I
Reference /Impurity standard inward register
| Sr. No. | Date of receipt | Name of Standard | Manufacture Name | Batch
/Lot No. |
Grade | Quantity Received | Potency | Water
/LOD |
Validity | Received By | Checked |
Annexure-II
Consumption Record- Reference/Impurity Standard
Name of Reference/Impurity Standard: –
Batch No./Lot No.: –
| Sr.
No |
Date of
Use |
Product/Item Name | Opening Balance | Qty Used | Balance Quantity | Used by | Checked by |
Annexure-III
List of working standard
| Sr. No. | Product Name | Storage condition | Valid up to |
Prepared by: Checked by: Head QC
Date: Date: Date:
Annexure – IV
Consumption Record- Working Standard
| Name of Working Standard | ||||
| Working Standard No./B.No./ A.R.No. | No. of Vials Prepared | |||
| Date of Analysis |
|
Use Before
|
|
|
| Potency (on as is basis %w/w) | Water/LOD Content (%w/w) | |||
| Sr.
No |
Date | Vial No. | Name of Product/Item | Stage | B.No/A.R.No | Opening
Qty |
Used Qty | Balanced Qty | Used by | Checked by |
Annexure -V
Working standard Issuance and Destruction Record
Name of Working Standard: _______________________________
Batch No./Lot No. of Working Standard:____________________________
Working standard Qualified On: _____________________ Valid up to: _______________
Number of Vials prepared:_______________________
| Vial Number | Quantity Filled | Quantity Issued | Issued by & Date | Destruction
done On |
Destroyed by | Checked By |
ANNEXURE-VI
Label for Working standard
| Name of working standard | :
|
Potency | : | ||
| Working Standard No. | : | LOD/Water | : | ||
| Prepared by | : | Vial No. | : | ||
| Valid from | : | Valid up to | : | ||
| Opened on | : | Use before | : | ||
| Note: After opening use within three month. | |||||
Annexure-VII
Certificate of analysis for working standard
| Name of Working standard | : | |||||||||||||||
| Working standard No. | : | |||||||||||||||
| Name of Manufacturer | : | Batch No | : | |||||||||||||
| Mfg. Date | : | Exp. Date | : | |||||||||||||
| Reference standard lot No. | : | Validity | : | |||||||||||||
| Reference standard/ material used for standardization | : | |||||||||||||||
| No. of vials prepared | : | Date of Preparation | : | |||||||||||||
| TESTS | SPECIFICATION | RESULT | ||||||||||||||
| Remarks: This material complies/ Does not complies as per specification and shall be used as Working standard in place of the reference standard as per above performed tests. | ||||||||||||||||
| Potency as is basis in % | : | |||||||||||||||
| Use vial within 3 months after opening | ||||||||||||||||
| Prepared By | Checked By | Approved By | ||||||||||||||
|
|
||||||||||||||||
| Officer QC | Executive/ Manager QC | Head QC | ||||||||||||||
Effective On: ______________________ Valid up to: _________________
Annexure-VIII
Reference/ Impurity standard validity period
Month:__________________
| Sr.
No. |
Name of Reference/Impurity
standard |
Batch No./
Lot No. |
Validity | Validity Verified By | Checked
By |
