Standard Operating Procedure for Receipt, Qualification and Handling of Analytical Standards
1.0 Purpose:
To lay down a procedure for Receipt, Qualification and Handling of Analytical Standards.
2.0 Scope:
The scope of this SOP is applicable for Procurement, Qualification, Storage, Handling and Disposal of Reference Standards (RS), Secondary Reference Standard/Working Standard (SRS/ WS), GC Standards used for Analysis in Quality Control Laboratory at [company name].
3.0 Responsibility:
3.1 QC-Personnel: To receipt, qualify, handling and destruction of analytical standards
3.2 Lab QA Reviewer: Review of Qualification report
3.3 Section Head-QC/ Designee:
- To check the qualification report.
- To monitor the activity.
3.4 Head-QC/ Designee : Ensure the Compliance of SOP.
3.5 Head- Lab QA/ QA/Designee: To approve the qualification report in LIMS.
4.0 Definitions and Abbreviations:
4.1 Definitions:
4.1.1 Pharmacopoieal Reference standard: These are authentic Substance of high purity with Critical characteristics and Suitable for their intended purpose. These are supplied by the official Pharmacopoieal.
4.1.2 In-House Reference standard: These are authentic substance, Characterized and verified In-House and suitable for their intended purpose.
4.1.3 Working standard/Secondary reference standard: Secondary Reference Standards are the standards that are Qualified against the current lot of the Reference Standard. Secondary Reference Standards are also known as Working Standard (WS).
5.0 Procedure:
5.1 Analytical standards shall be accessed to authorized personnel. List of authorized personnel having access to Analytical standards shall be prepared by lab support person in the format titled “List of QC/QA/Lab QA persons authorized to access standards”. The List shall be displayed at the Analytical standards storage room.
5.2 The list shall be updated whenever required like when the authorized person left from the organization or when any new person is authorized.
5.3 During handling of analytical standards, wear Personal Protective Equipment (PPEs) like hand gloves, safety goggles, nose mask (as appropriate).
5.4 Never transfer the remaining quantity into the original container after completing the weighing activity.
5.5 In case of Liquid standards transfer the material in the clean glassware and after weighing don’t transfer the remaining quantity into the original container.
5.6 Fresh working standard vial shall be used every time during analysis. Once opened, vial shall be discarded after the analysis is complete.
5.7 At the time of usage, analyst shall ensure the correctness of the standard vial against the specification like name of the standard, lot number and validity period.
5.8 If any abnormality found (Wrong standard issued / Lot no., WS not within the validity period) then, do not use the vial and inform to lab support person accordingly.
5.9 Before using / weighing the reference standard or working standard, keep the standard vial in the Desiccator/ Tray provided to attain the room temperature or as per the requirement.
5.10 If the working standard is exhausted before its validity period qualify new working standard against the current lot of reference standard.
5.11 If the potency of Analytical Standard is more than 100%, it shall be considered as 100%.
5.12 Temperature record for the cooling cabinet / deep freezer / dual chamber record shall be verified on daily basis. For weekly off/ holiday, temperature record shall be verified on next working day.
5.13 After opening, the Analytical standards are closed tightly with the Para film/aluminum Crimp Cap after every usage and shall be kept in the upright position in respective chamber by Lab support Person.
5.14 If analytical standard is required to be dried before use then, use a cleaned and dried weighing bottle for drying. Do not use original container as drying vessel for drying.
5.15 Reference standard which is required for RT / RRT or resolution and which are not used for any quantitative estimation, the usage quantity of such reference standard can be reduced where, the final concentration shall be kept as per the test procedure with prior approval from department head.
Note: In case, where statement mentioned on the reference standard “Reconstitute and quantitatively transfer the entire contents of the vial without weighing” and for protein & peptide where ever applicable lower weight of reference standard may be used for working standard qualification. Final concentration of the solution will remain similar.
5.16 Lab support person shall verify all the analytical standards on monthly basis and same shall be update in LIMS.
5.17 In case Identification test by IR for packaging material “Reference Standard / Vendor Spectra shall be considered as working standard.”
5.18 Procurement, Receipt and Storage of Analytical Standards:
5.18.1 The different analytical standards used in the laboratory are:
- Reference Standard (RS) or Primary Reference Standards (PRS)
- Secondary Reference Standard (SRS) or Working standard (WS)
- Impurity Standard
- GC standards
5.18.2 Analytical standards shall be procured from authentic source or can be received from Company’s other locations.
5.18.3 Reference Standard (RS / PRS)
- Reference standards are authentic standards received from Pharmacopoeial commission.
- Procure the reference standards from stipulated source i.e., USP, BP, EP, IP, Micromol , GMBH or from official distributor. i.e. Promochem.
- Reference standards / impurity standards (Other than Pharmacopoeial) shall be procured from API vendors.
- Lab support person shall initiate reference standard procurement, at least two months prior to its requirement.
- Lab support person shall raise the procurement requisition in SAP with the details of RS like name of the material, quantity required etc., and shall forward the requisition to purchase department.
- During receipt of RS, Lab support person shall verify following details (but not limited to)
i. Name of the material for which requisition has raised.
ii. Lot Number (Current Lot).
iii. Use before / valid up to / expiry date/re-test date (as applicable).
iv. Documents received along with the RS (Invoice, Delivery Note, MSDS, COA, etc.).
v. Storage condition
- If any abnormality observed then, it shall be informed to Purchase department.
- The validity of reference standard shall be checked for current lot by referring current catalog, confirmation from authorized source and through respective web site. For example:
USPRS: www.usp.org
EPCRS: www.edqm.eu
BPCRS: www.bpcrs.com
IPRS: www.iprs.com
- If all the above details are found satisfactory, then the Reference Standard/Impurity shall be received and updated the inventory in LIMS.
- The received standard shall be stored in chamber according to its storage condition.
- If, RS/Imp/WS is procured from other than API vendors like Simson etc. as per approved supplier list then, complete analysis report is attached with the characterization data, whenever required.
- If analytical standards are received with similar name from different vendors then, nomenclature (IUPAC name / other synonyms) and Pharmacopoeial name (if any) shall be verified and difference (if any) shall be mentioned on vial and inventory shall be done in LIMS.
- Lab support person shall verify all the RS stored in QC lab on monthly basis against current official catalog of USP/EP/BP.
- In case, any lot is found expired, quantity / No. of vials of the expired lot shall be verified and removed from respective storage chamber and properly segregated. Expired lot shall be discarded and same disposal entry shall be done in LIMS.
- Current lot of reference standard shall be used up to its validity period.
- In case, the RS found expired/Material is not available at site and required for the analysis, then site lab support person can request company’s other location to procure / send the analytical standard which is not available at site.
- At the time of receipt of Analytical Standards, if the documents like COA or any relevant data is not provided. In that case, the standards are stored in the separate container/box according to the storage conditions.
- Respective site shall send the analytical standard by courier along with data logger whenever required.
- At the time of receipt of standard, lab support person shall verify the minimum, maximum and average temperature in data logger. If the data logger does not show Min, Max and Average temperature, then complete data is required. If Data is found satisfactory then, the standard inventory shall be done in LIMS.
- If the temperature is not within the limit, Stability data and relevant supporting information shall be requested and verified for evaluation. Based on evaluation of data working standard shall be accepted/ rejected.
- After receiving of standard, QC shall request respective site to send complete transit data of Data Logger.
- QC shall verify the transit data. If found satisfactory, then only be issued for routine use and details of transit data shall be kept for record.
5.18.4 Working Standard (WS)
- WS shall be internally qualified against the current lot of Reference Standard.
- If any WS is received from other location and vendor, shall be kept as per storage condition mentioned in respective Certificate of Analysis.
- During receipt of WS, lab support person shall verify following details (but not limited to)
i. Name of the material for which requisition has raised.
ii. Lot Number (Current Lot).
iii. Use before / valid up to / Expiry date/Re-test (as applicable).
iv. CoA of Reference Standard / API by which WS is qualified
v. Documents received along with the RS (Invoice, Delivery Note, MSDS, COA, etc.).
vi. Storage condition
- Validity of WS shall be less than/equal to the material (API) by which WS is qualified.
- QC personnel verify the material received along with the label and supporting documents received.
- If any abnormality observed then, it shall be informed to respective site.
- If all the above details are found satisfactory, then the WS shall be received and inventory shall be created in LIMS.
- The received standard shall be stored in chamber according to its storage condition.
5.18.5 GC Standards
- GC standards shall be Procured from approved source like Merck, SDFCL, Fluka, Spectrochem, etc. (but not limited to).
- The requisition shall be forwarded through mail to the purchase department specifying the name of the standard, quantity required etc.,
- The material is received by store department and after inventory in SAP the material is handed over to QC person.
- After receiving the standard, the QC person shall verify the certificate of analysis and the same shall be filed.
- During receipt of GC standard, lab support person shall verify following details (but not limited to):
i. Name of the standard for which requisition has raised.
ii. Lot Number.
iii. Use before / valid upto / Expiry date/re-test date (as applicable).
iv. Certificate of Analysis
v. Purity of the standard
vi. Documents received along with the standard (Invoice, Delivery Note, MSDS, COA, etc.).
vii. Storage condition
- The purity is assigned on the basis of the certificate of analysis received from the supplier or manufacturer. Such received material are not further qualified and neither subsequent standards are prepared against these materials.
- List of GC standard list be updated/verified on monthly basis or whenever required. If any new addition of standard,Inventory shall be done in LIMS.
- The use before date for GC standard chemicals shall be based on chemical nature or maximum 6 months from the date of opening.
- Validity of GC standard (other than sensitive chemicals) shall be as per the expiry specified on the supplier’s COA / bottle or maximum 1 year from the date of opening whichever is minimum
5.18.6 Qualification of Secondary Reference Standard (Working Standard) :
- Material selected for qualification of working standard should be a recent / current lot of approved raw material with highest purity/potency.
- Available lot with highest purity Approved (As per release COA) /under test (As per Vendor COA) material shall be used for working standard Qualification.
- To get the approved raw material from Warehouse department, QC personnel shall prepare a material requisition note in format titled “Material requisition Format” and after getting approval from QA the requisition shall be submitted to Warehouse in charge.
- On the basis of material requisition, the requested quantity of the material will be sampled by QC personnel as per sampling procedure.
- Use current lot of reference standard for qualification of working standard.
- During qualification of working standard ensure that, validity of reference standard should not pass its original expiry date.
- Secondary Reference Standards are the standards that are Qualified against the current lot of the Reference Standard. Secondary Reference Standards are also known as Working Standard (WS).
- If the WS is to be qualified using under test material, then required sample quantity shall be taken from already sampled material.
- If WS is qualified using under test material, then the WS shall be made effective only after approval of under test material.
- WS qualification shall be qualified as per respective raw material Specification.
- Description, Identification, LOD/Water Content & Assay tests shall be performed for qualification of Working Standard.
- If WS received from other locations then, the WS shall be received along with COA. Based on the COA, WS shall be used for routine analysis.
- In case under test material is used for Secondary Reference standard qualification, after approval of raw material, QC personnel shall prepare a material requisition note in format titled “Material requisition Format” and after getting approval from QA the requisition shall be submitted to ware house – in charge & On the basis of material requisition, the approved quantity of the material will be sampled by QC personnel as per sampling procedure.
- Record the Reference Standard consumption in LIMS.
- QC Person shall perform analysis in LIMS.
- Attach the HPLC / UPLC, UV Spectra, IR spectra or if any in LIMS.
- To qualify the secondary reference standard the test assay and LOD / Water content shall be carried out in triple sets and all other remaining tests shall be carried in a single set by single analyst.
- For calculation of Assay test on dried basis / anhydrous basis, mean of the three set of LOD / Water content is taken, respectively.
- The Relative standard deviation (% RSD) for Assay in triplicate set shall not be more than 1.0 % and the average of Assay is considered as the assay of WS.
- If the % RSD between the assay results found more than 1.0 % then, qualification of WS shall be repeated by another analyst in triplicate.
- If the % RSD between the Assay results of second analyst is within 1.0 % then, second analyst result shall be considered as valid and investigate for initial failure.
- After completion of WS qualification, report shall be verified by Lab QA reviewer and approved by Lab QA / QA.
- Finally, Head-Lab QA/QA/Designee shall approve the qualification report in LIMS.
- After approval from Head Lab QA/QA/Designee in LIMS, QC Person shall take the print of Certificate of Analysis (COA) from LIMS if required.
- For qualification of In-House Working standard and for those where reference standards are not available with Pharmacopoeia Commission, then such Working standard shall be sent to Research and Development laboratory to perform the characterization study and complete record of the characterization shall be maintained at the site.
- After completion of qualification, WS shall be stored in respective chamber as per the applicable storage conditions.
- The impurity standard/Working standard and reference standard received from R&D (Other than Pharmacopoeial standard) shall be kept as per storage conditions mentioned in respective Standards/Impurities Certificate of analysis.
5.18.7 Procedure for Vial Filling:
- All Working standard material shall be transferred to amber color glass vials with rubber caps and sealed with aluminum cap as per the requirement.
- Working standard vials filling activity shall be done in Laminar Air flow as per respective procedure.
- Qualified working standard shall be filled in each and individual vials as per the requirement up to its vial capacity (Approximately 50 – 600 mg).
- In case of sodium meta bisulfite and Sevelamer carbonate standard received from other source and which is not to be qualified at site, it shall be filled in each different vials as per usage, up to vial capacity immediately.
- The Working standard vials are labeled in the Format titled “Working Standard Label” for container. Each and individual vial shall contain the minimum information of WS name, WS number, Potency, vial No. and Water content/ LOD. The In-house Impurity standard vials shall be labeled in the Format titled “In-house Impurity /Reference Standard Label”
- Transfer all the filled vials of working standards in the cooling cabinet/deep freezer as per the storage condition mentioned on the standard vial.
5.18.8 Assigning of Shelf life to Analytical Standards:
- The validity of WS shall be given one year or shelf life of the API whichever is less.
- R&D / Vendor, Working Standard / Impurity Standards shall be used till its expiry date.
- Lab support person shall ensure the validity of working standard. The validity of WS should be less than the API which is used to qualify WS.
- Validity of GC standard shall be as per the expiry specified on the supplier’s COA / bottle or else validity is considered to be 1 year from the date of opening and based on chemical nature or maximum 6 months from the date of opening.
- To assess the stability of working standard, assay and LOD or water content to be performed in single set analysis to ensure that there was no significant change during the storage. The retest results shall meet the acceptance criteria of the relevant specification and that should not differ by more than 1% in assay from its initial value obtained during WS qualification.
- If the significant change is observed more than 1%, then further investigation shall be carried out.
- The assessment of Stability of Working Standard shall be checked after six months and expiry on the basis of Protocol. If no significant change is observed in that period then there shall be no further assessment to be carried out as the Standard is in stable condition.
- The Validity for Analytical Standards provided by the vendor for (Retest/Expiry/Valid up to/due date) shall be in the Format of Month & year. Then, the validity shall be considered in the Format of last date of Month &year.
For example :If the Valid up to Month &date is Jun 2020, then it shall be considered as last date of Jun 2020
5.19 If any abnormality is observed before the expiry of the standard, i.e. in the appearance (color change of the liquid standard), then it is discarded.
5.20 Issuance of Analytical Standards:
5.20.1 Lab support person shall issue the standard vial in chronological order.
5.20.2 All WS/Imp/RS vial should be issued from LIMS prior to analysis by Lab support Person/ authorized person.
5.20.3 Working standards (multiple vials/single vial) received from R&D and other sources inward and consumption shall be done in LIMS.
5.20.4 In case LIMS under shutdown/breakdown working Standard/ reference standard/impurity standard consumption shall be record after resumes the LIMS.
5.20.5 Make necessary Working Standard (received from outside) Consumption entry shall be done in LIMS.
5.21 Handling of Analytical Standard:
5.21.1 Take required quantity from the vial.
5.21.2 Do not return dispensed quantity of material into the vial.
5.21.3 The reference standards shall be collected in container kept for designated purpose in chemical lab from its original pack.
5.22 Assigning of numbering for Analytical standards:
5.22.1 Assign the reference number to Reference Standard as follows,
REF/CM/YY/ZZZ-NNNNN
REF – Reference standard
CM- Company
YY – First two digits of the current year and
ZZZ- Serial No.
NNNNN-Serial No
5.22.2 Assign the reference number to Working Standard as follows,
WS/AAAA/XXX/CM/YY/ZZZ-NNNNN Where,
WS – Working standard
YY – Current year
AAAA – First four alphabets of material used for preparation of Working Standard
XXX – Pharmacopoeia reference
CM -Company
ZZ Z – Serial number 001, 002, 003…. The number of working standard in the corresponding year.
NNNNN- Serial no 00001, 00002, 00003….
5.22.3 Impurity standard:
Assign the reference number to Impurity Standard as follows,.
IMP/CM/YY/ZZZ-NNNNN
IMP– Impurity standard
CM-Company
YY – First two digits of the current year and
ZZZ – Serial No.
NNNNN- Serial No
5.22.4 GC standard – Assign the reference number to standard as follows;
GCS/CM/YY/ZZZ-NNNNN
GCS – GC Standard
CM – Company
YY – Current year (For 2022)
ZZZ-Serial No
NNNNN- Serial No
5.22.5 If outside working standard received, Assign the reference number to working standard as below:
WS/AAAA/XXX-Ext/CM/YY/ZZZ-NNNNN
Where ,
WS – Working standard
AAAA – First four alphabets of material used for preparation of Working Standard
XXX – Pharmacopoeia reference
Ext – External
CM -Company
YY – Current year
ZZZ – Serial number 001, 002, 003…. The number of working standard in the corresponding year.
NNNNN- Serial no 00001, 00002, 00003….
5.23 Disposal of Analytical standards:
5.23.1 Dispose the working standard vial, if it is exhausted.
5.23.2 Destroy the expired reference standards as per the discarding procedure of Hazardous waste.
5.23.3 Remove the material waste in hazardous waste bin and discard the bottle in respective waste bin and hand over to EHS department.
5.23.4 Each single vial after opening shall be used for analysis and discard the same vial after use on the same day in LIMS.
5.24 Secondary Reference Standards for Gas Chromatograph :
5.24.1 The stock of such standards is stored at laboratory conditions.
5.24.2 The vials are identified by label in the Format titled “GC Working Standard Label”.
5.24.3 Destroy the expired reference standards by draining in running water.
6.0 Acceptance Criteria:
6.1 For Secondary Standard (Working Standard): The Relative standard deviation for Assay in triplicate shall be not more than 1.0 %.
6.2 For retesting the results shall meet the acceptance criteria of the relevant specification and that should not differ by more than 1% in assay from its initial value obtained during WS qualification.
7.0 Frequency:
7.1 As and when required
7.2 Reference standards verification – Monthly
7.3 Assessment of Stability of Working Standard-Half yearly
9.0 Format for recording:
9.1 List of QC/ QA person authorized to access standards
9.2 Reference Standard /Working Standard/Impurity Standard Inward Register.
9.3 Material Requisition Format
9.4 Certificate of Analysis for Working Standard.
9.5 Working Standard Label
9.6 GC Working Standard Label
9.7 List of GC Working Standard.
9.8 Working Standard Consumption Record Logbook.
9.9 List of Reference Standard/Impurity Standard/ working standard.
9.10 Check list for New standard Procurement.
9.11 Working Standard/ Reference standard/ Impurity standard Consumption Record.
9.12 In house Impurity/ Reference Standard Label
9.13 Distribution list of SOP and Formats/ Annexures.
Format for List of QC/QA/Lab QA person authorized to access standards
| Sr. No. | Name of the Person |
| — | Prepared By | Checked By | Authorized By |
| Sign & Date | |||
| Designation | |||
| Department |
Reference Standard /Working Standard/Impurity Standard Inward Register.
Name of Reference Standard :
Storage Condition :
Date of Receipt
Batch No. / Lot. No.
Source
Quantity Received
Supplier Challan No. & Date
Use for Product
Received By & Date
Use before
Remarks
Format for Material Requisition Format
| Material | : | |
| Item Code | : | |
| Batch No. | : | |
| A. R. No. | : | |
| Pharmacopoeia / IH | : | |
| Purpose | : | |
| Quantity | : | |
| Remark | : |
| Initiated By | Checked By | Approved By | ||
| Signature & Date | ||||
| Designation | ||||
| Name | ||||
| Department | Quality Control | Quality Control | Warehouse | Quality Assurance |
Certificate of Analysis for Working Standard.
NAME OF WORKING STANDARD :
Batch Number :
A.R.No. :
Quantity Prepared :
Date Of Preparation :
Use Before :
Storage Condition :
Working standard reference number :
Specification Reference no. :
Evaluated with :
Reference SOP Number :
| Test | Result | Standard |
Remarks: The above material matches with reference standard with respect to identity, purity and can be substituted.
| Analyzed By | Checked By | Approved By |
| Date : | Date : | Date: |
Format for Working Standard Label
Name:
WS No.:
Potency (on as is basis):
LOD/Water content:
Vial No.:
Use Before:
Storage Condition :
Format for GC Working Standard Label
STANDARD FOR GAS CHROMATOGRAPHY
Name :
Lot No. : Ref. No. :
Purity : Expiry :
Opening Date : Vendor :
Format for In house Impurity/Reference Standard Label
Name:
Batch No:
Reference No.:
Potency :
Use Before:
Storage Condition :
List of GC Working Standard
| Sr. No. | Name Of GC Standard | GC Ref. No. | Make | Purity | Expiry Date | Remarks |
Working Standard Consumption Record Logbook
| Name of working standard | : | |
| Vial Issue Date | : | |
| Assay (as is basis ) | : | |
| Storage Condition | : | |
| Entry Done by |
| WS Ref.No | : | |
| Vial Valid up to | : | |
| LOD/Water content ( % ) | : | |
| Open on date | : | |
| Verified by |
| Date of Use | Initial Quantity | Used Qty | Remaining Qty | Stage | Material Name/ Product Name | Batch. No. | Test | Sign | Remarks |
List of Reference Standard/Impurity Standard/working standard.
| Sr. No. | Name of The Standard | Source | Lot No. / Batch No. | Potency | Storage Condition | Use Before | Remarks |
| — | Prepared By | Checked By |
| Signature | ||
| Date |
Check list for New standard Procurement
| Sr.No. | Checkpoints | Mentioned Name | Verified By |
| 1. | Name of Standard | Found OK/Not OK/NA | |
| 2. | IUPAC Nomenclature | Found OK/Not OK/NA | |
| 3. | Required Quantity | Found OK/Not OK/NA |
| 4. | Synonyms as per Pharmacopoeia |
| USP | Found OK/Not OK/NA | |
| BP | Found OK/Not OK/NA | |
| IP | Found OK/Not OK/NA | |
| Others (If any Mentioned)__________ | Found OK/Not OK/NA |
| 5. | Vendor In-House Nomenclature |
| Harman | Found OK/Not OK/NA | |
| Promochem | Found OK/Not OK/NA | |
| Others (If any Mentioned)_________ | Found OK/Not OK/NA |
| Prepared By | Checked By | Approved By | |||
| Sign/Date | Sign/Date | Sign/Date |
Working Standard/Reference standard/Impurity standard Consumption Record.
| Sr.No. | Name of the Standard | Lot No/Batch No. | Vial No. | Issued on | Name of the Product | Batch No./A.R.No. | Name of the Test | Used Quantity | Used Date | Used By | Checked By | Remarks |
