Guidelines for Receipt and Usage of Reference Standards and Qualification and Usage of Working Standards
REFERENCE STANDARDS & IMPURITY REFERENCE STANDARDS
Reference standards are authentic substances that have been approved by Reference Standards approving authority as suitable for use as Comparison Standards in various tests described in individual monographs and methods of analysis.
Wherever possible pharmacopoeial reference standards and impurity reference standards shall be procured.
If pharmacopoeial reference standards including those for impurities are not available, the same can be procured from chemical research laboratories, drug substance manufacturer, contract giver or in-house reference standards shall be used.
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Receipt of Reference Standards :
On receiving a reference standard the following checks are carried out.
• Quantity received against the challan / invoice.
• Lot No. or Batch No. of the respective reference standard from the vial and certificate of analysis, if available.
Record the details in the index of the reference standard log book. These details include Sr No., Name of Reference Standard, Pharmacopoeial status, Supplier Name and Page Number.
On the header part of the respective page for any reference standard, record the details viz. Name of the reference standard, Lot Number / Batch Number, Assay (as is), Quantity received, Supplier Name, Pharmacopoeial Status, Date of Receipt, Mfg Date & Expiry Date / Validity if available.
Assay shall be recorded as 100%, if not claimed on the vial or on the certificate of analysis of reference standard.
Storage of Reference Standards:
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Store the reference standards and impurity reference standards in original vial/container or in a suitable container if necessary.
Keep the containers airtight protected from heat, moisture and light.
Store the reference standards at the recommended or prescribed storage conditions. If storage conditions are not recommended by the pharmacopeia, manufacturer or supplier, store between 2°C to 8°C
Usage of Reference Standards:
Reference standards shall be used for analysis or qualification of working standards, as and when required. Impurity reference standards shall be used for analysis for various tests as per requirement.
Handle the reference standards carefully. Ensure that the integrity is safeguarded and maintained throughout their period of use.
Do not insert spatula or butter paper in the vial. Transfer required quantity approximately on butter paper and discard the remaining quantity taken out. Do not transfer the balance quantity to the original vial.
When a vial of the reference standard is taken out from the respective storage conditions, allow it to attain the room temperature prior to use. After weighing of the standard, store the vial in prescribed storage conditions.
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Recommendations from manufacturer/supplier shall be followed before every use. Such recommendations may include estimation of water content, vacuum drying etc.
Also, record the consumption of reference standard in the log book. Record Sr No., Vial opened on Date, Date of Usage, Balance No., Quantity Taken (Approximate), Test, Taken by and Checked by in the logbook.
Reference standards shall not be used after their expiry date/validity
Disposal:
The outdated reference standards and empty vials shall be destroyed to prevent misuse. Deface the label of such vials before destroying. Such disposal shall be recorded in the reference standard logbook.
WORKING STANDARDS
Working standards are the materials of high purity, which are used as a substitute for reference standards and are qualified against reference standards or authentic standards.
Qualification of Working Standards
For qualification of working standards select an approved batch of respective raw material preferably of current lot/batch having purity well above lower specified limits.
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Qualify fresh working standard by comparing with a current lot of pharmacopoeial reference standard available. If a pharmacopoeial reference standard is not available, standard provided by chemical research laboratories, drug substance manufacturer/contract giver or certified in-house reference standards shall be used for qualification of working standard. Existing working standard can also be used to prepare new working standard if the results of retesting of existing standard are within specified limits.
Perform following tests during preparation/qualification of working standard.
• Description
• Identification (IR spectrum shall be recorded whenever possible and compared with reference standard or authentic standards. Lot number of reference standard used shall be incorporated on the IR spectrum)
• Water content (shall be performed in triplicate) or
• Loss on drying
• Assay (perform the assay in triplicate. RSD of the result obtained should not be more than 1.0 %.)
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Report the assay on as is basis. If the assay of working standard obtained is above 100%, it shall be reported as 100% on the label.
Record the details of qualification of working standard i.e. manufacturing date, batch number, reference standard details used in preparation and valid up to etc. Document all the data including relevant spectra and / or chromatograms and reports along with certificate of analysis with a complete information as to test methods employed, values obtained for each test, as applicable.
If the working 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 working standard analytical report. A working standard number is assigned to such working standard and recorded.
Working Standard Numbering:
All working standards, whether prepared in-house or supplied by external party shall be numbered. Assign the working standard numbers as follows:
Number the working standard as WS/XXX-SS/YY,
Where,
WS : for Working Standard,
XXX : abbreviation of ma1terial defined for this purpose
SS : is the pharmacopoeial status of the standard. For example, IP for Indian pharmacopoeial standard, USP for United States pharmacopoeial standard, EP for European pharmacopoeial standard and IH for in-house or non-pharmacopoeial standard.
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YY : is Serial Number starting from 01 for each material.
e.g. WS/IBU-EP/01, where WS – Working Standard, IBU – Ibuprofen, EP describes the pharmacopoeial status of Ibuprofen i.e. Ph. Eur., 01 – First working standard in series. The second working standard of Ibuprofen qualified shall be numbered as WS/IBU-EP/02, the third as WS/IBU-EP/03 and so on. Non-pharmacopoeial impurities shall also be numbered accordingly with a suitable abbreviation for impurity name.
Packing and Storage of Working Standards
Fill approximately equal quantity of the working standard in 13 amber colored vials. Filling of these vials shall be carried out under reverse laminar air flow. Label these vials month wise, one for each month from the month of preparation. These vials shall be used, one for each month for the successive twelve months from the date of preparation. The additional 13th vial is kept as control vial and shall be used in case any vial of the twelve vials get exhausted or damaged. In event, more vials or quantity is expected to be consumed; two or more vials per months shall be prepared. Document the filling of working standard vials record.
Validity of 1 year from the date of qualification shall be assigned to working standard
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For the compounds which are known to be unstable, shorter validity periods shall be assigned. Shorter validity period shall also be assigned based on the expiry date of raw material used in the qualification of working standard
Label these working standard vials.
• Name of working standard
• Working standard number
• Month
• Date of Qualification
• Valid up to
• Assay (as is)
• Storage Condition
Store the working standards at the recommended or prescribed storage conditions. If storage conditions are not recommended by the pharmacopeia, manufacturer or supplier, store between 2°C to 8°C.
Keep the vials air-tight protected from heat, moisture and light.
Usage of Working Standards
Record the details in the index of the working standard log book. These details include serial No., Name of working standard, Pharmacopoeial status, supplier and Page Number.
On the header part of the respective page for any working standard, record the details like; Name of the working standard, batch number, working standard number, assay (as is), pharmacopoeial status, effective date and validity.
Also, record the consumption of working standard in the log book. Record serial number, Vial Opened on, date, balance number, quantity is taken (Approximate), test, taken by and checked by in the log book.
Handle the working standards carefully. Ensure that the integrity is safeguarded and maintained throughout their period of use.
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Do not insert spatula or butter paper in the vial. Transfer required quantity approximately on butter paper and discard the remaining quantity taken out. Do not transfer the balance quantity to the original vial.
After usage, securely close the vial and store as recommended.
When vial of working standard is taken out from the respective storage conditions, allow it to attain the room temperature prior to use. After weighing of the standard, store the vial in at prescribed storage condition.
Do not use the working standard, if any change in description during storage is observed. An investigation shall be made to find out the change and documented. Alternatively replace the working standard as soon as a significant change in such property is observed.
The working standard shall not be used after the validity period.
Prepare the fresh working standard in the last month of the validity of the existing working standard.
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Retest the working standard after one year. Perform following tests while retesting
• Description
• Identification (IR spectrum shall be recorded whenever possible and compared with reference standard or authentic standards)
• Water content (shall be performed in triplicate) or
• Loss on drying
• Assay (perform the assay in triplicate. RSD of the result obtained should not be more than 1.0 %.)
Compare the results of retesting with the initial results. The results should be within the specified limits and comparable with the initial results. In event, the results of retesting not meeting the acceptance criteria, the analysis in which the concerned working standard had been used, shall be evaluated.
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Document the retesting results.
Disposal
The remaining quantity of standards and empty vials shall be destroyed to prevent misuse. Deface the label of such vials before destroying. Such destruction shall be recorded in the working standard logbook.