SOP: Storage And Use of Chemical Reference Substances in the QC Laboratory
ABBREVIATIONS AND DEFINITIONS
API: Active Pharmaceutical Ingredient
BP: British Pharmacopoeia
COA: Certificate of Analysis
EP: European Pharmacopoeia
EDQM: European Directorate for the Quality of Medicines
IR: Infra-red
MSDS: Material Safety Data Sheet
QC: Quality Control
QA: Quality Assurance
RS: Reference Standard
USP: United State Pharmacopoeia
UV: Ultra-violet
Chemical Reference Substance (CRS): Chemical reference substances are authentic substances that have been approved by Reference Standard approving authority as suitable for use as comparison in various tests described in individual monograph and method analysis.
Sub batches (EP): Sub batches are obtained by filling containers with material from the same batch of bulk material. The quality and specification of the sub-batches do not differ from each other. Currently, sub batches are labeled as 1.1, 1.2, 1.3, etc.
Current Lot (USP): Current lot designation of each official item being distributed as of the date of this catalog. If the current lot is blank, the item is not in distribution.
Previous Lot/Valid Use Date (USP): Lot designations for recent lots no longer being distributed. The date in parentheses indicates the month (last day of the month) through which that lot was valid as an official USP Reference Standard (e.g. "F-1 (30-SEP-2021)" means lot F-1 is no longer being distributed, but was considered official through September 30, 2021).
PRECAUTIONS
1. Immediately recap the CRS container after its opening and care must be taken during weighing, use a clean and dry spatula during withdrawing the material.
2. For USP RS, consider potency as 100% unless potency is specified in the respective CRS container label and for BP/EP CRS follow potency specified in the respective leaflet or on-line catalogue. For BP/EP CRS, if the potency is not mentioned for the active substances, then these CRS can only be used for qualitative analysis.
3. When use an impurity reference standard in a related substances test for the control of an impurity and if no assigned content is indicated, the purity of the reference standard for the purpose of estimation is considered to be 100 percent.
4. For non-pharmacopoeial CRS, use potency referring to the respective certificate.
In case of CRS stored in freezer or refrigerator, prior to use wipe the outer surface with the tissue paper to remove the condensed moisture and shall be transferred to the desiccators to attain the room temperature.
5. Where drying of the CRS is specified, only the required portion of the CRS should be dried in a Petri dish before using.
6. CRS should be stored alphabetically in its designed place. (As per storage condition)
For pharmacopeial CRS/ RS, do not receive any CRS/RS which is from old lot/ invalid lot.
PROCEDURE
01. Current lot checking procedure:
1.1. Officer to Sr. Executive, QC shall log-on to following web address for checking the Current lot of CRS:
For BP CRS: https://www.pharmacopoeia.com/Catalogue/Products
For EP CRS: http://crs.edqm.eu/
1.2. Officer to Sr. Executive, QC shall search for the CRS required for and check for the available current batch (lot) (BP CRS)/ current lot (USP RS) or Batch (EP CRS). For USP RS, in some cases Previous lot might be mentioned with a validity date in the list, in this case same can be used. For EP CRS Current lot is valid for all sub lot/batches for example if current lot/batch of any CRS shown in EDQM site is 2 then all sub batches 2.1, 2.2, 2.3 is valid for this lot/batch.
1.3. Officer to Sr. Executive, QC shall Compare the batch number to Stock CRS/ RS with “Current lot/ Batch” of catalog.
1.4. If any CRS is excluded from “Current lot” list, Officer to Sr. Executive, QC shall place a fresh requisition for the same, until receiving of the same use the existing CRS, upon receiving of the current lot of CRS discard the old batch of CRS using internal requisition and issue in IFS software.
1.5. Officer to Sr. Executive, QC shall check the current lot status monthly (Preferably 1st week of every month) and update the CRS list.
1.6. Prior to use of a CRS, Officer to Sr. Executive, QC shall check lot/ batch number against the CRS list, if the existing CRS lot/ batch match with the Current lot, use the same and if does not meet then inform the responsible person for raising fresh requisition for the same. Purchase requisition should be raised for INN CRS before about six months of their expiry date and for USP RS, EP CRS and BP CRS before about four months of their expiry date using IFS software.
2. Receiving and Storage:
2.1. Officer to Sr. Executive, QC shall receive CRS from authorized source i.e. USP/ EP/ BP or API Manufacturer/ Research Laboratory.
2.2. Officer to Sr. Executive, QC shall receive CRS with respective certificate and check the certificate by giving checked by signature and date. Also receive in IFS software as Register Arrival which is described in appendix-F
2.3. During receiving, Officer to Sr. Executive, QC shall check the outer labeling of the CRS i.e. name, lot number, storage condition, and check the outer condition of the container i.e. flip-off sealing and intact condition. Also check the current lot status for Pharmacopeial CRS/ RS (Follow step 1.1). If any discrepancy observed during receiving send back it to SCM department.
2.4. After receiving, Officer to Sr. Executive, QC shall affix a label on the CRS container, bearing information of CRS Control no., received date, open date, expiry date and storage condition. After opening, Officer to Sr. Executive, QC shall input open date and expiry date (if required).
2.5. Officer to Sr. Executive, QC shall Issue Code no for each type of CRS in alpha-numeric digits and start with first alphabet corresponding to the respective CRS name, then use numeric value e.g. for Dexamethasone CRS Code no is D1, then for Dexamethasone Sodium Sulphate CRS Code no is D2.
2.6. Officer to Sr. Executive, QC shall issue CRS control no. for every CRS in alpha-numeric digits and start with the Code no. of respective CRS then place a slash than (three) numeric digits e.g. if four vials of Dexamethasone CRS received than the CRS control no will be in following order: D1/001, D1/002, D1/003 & D1/004 respectively, where, D1 is the code no. for Dexamethasone CRS. Use CRS according to the consequence of CRS control no.
2.7. Officer to Sr. Executive, QC shall store the CRS as per storage condition:
In case of USP RS storage condition is usually noticed on the RS label i.e. at refrigerator (2- 8ºC) or at freezer (-20ºC) and if nothing is mentioned then store the RS in room temperature on the desiccators over activated silica gel and change silica gel immediately with the dried one whenever it becomes fade.
3. Expiry dating
3.1. Officer to Sr. Executive, QC shall use current batch (lot) of BP CRS/ current lot of USP RS or Current Batch of EP CRS.
For USP RS, in some cases Previous lot might be mentioned with a validity date in the online list/catalog, in this case same is ready for use.
3.2. Officer to Sr. Executive, QC shall use BP CRS as long as the batch (lot) number on the vial is shown as the current batch (lot) on the website, it is valid and suitable for use, provided it is unopened and stored according to the instructions.
3.3. If the batch (lot) number on the BP CRS vial is different from the current batch (lot) on the
website, then Officer to Sr. Executive, QC shall apply an expiry date of 12 months from the
date of dispatch provided if it is un- opened and stored according to the instruction given.
9.4. In case of CRS received form API manufacturer/ Research Laboratory, Officer to Sr. Executive, QC shall give expiry as per respective Certificate of Analysis (COA).
4. Use & discard of CRS:
10.1. Officer to Sr. Executive, QC shall check the current lot status of required CRS following step 1.1 and use current lot of available CRS/ RS for analysis.
4.2. Officer to Sr. Executive, QC shall check the expiry date (if any).
4.3. Officer to Sr. Executive, QC shall take the CRS from the desiccators/refrigerator/ freezer.
4.4. Officer to Sr. Executive, QC shall keep it few minutes and follow the SOP of Handling of Desiccators to attain room temperature if taken out from refrigerator/freezer.
4.5. Officer to Sr. Executive, QC shall weigh quickly with minimum exposure to air.
4.6. Officer to Sr. Executive, QC shall close the container tightly and wrap the cap with Para film & keep it in the dedicated place.
4.7. Officer to Sr. Executive, QC shall place an internal requisition for the quantity used and take approval from the Deputy Manager/Sr. Assistant Manager/Sr. Executive. Also raise an internal requisition to the IFS software.
4.8. Officer to Sr. Executive, QC shall input the reconciliation status on CRS logbook. Also issue the used CRS from IFS software.
4.9. Officer to Sr. Executive, QC shall store and use the prepared CRS solution used for qualitative test at 20C - 80C for three months, unless otherwise specified in the individual monograph/method.
4.10. Officer to Sr. Executive, QC shall describe CRS solution preparation into Logbook for CRS Solution preparation
4.11. Officer to Sr. Executive, QC shall Use reference no: CRS/XXXX/MM/YY
Where XXXX-serial no, MM-current month, YY-Last two digit of current year
4.12. Officer to Sr. Executive, QC shall discard INN CRS immediately after their expiry date and use the stock USP RS, EP CRS and BP CRS until receiving of fresh Lot/Batch of RS and CRS. The old batch of RS and CRS will be discarded after receiving of the current lot of RS and CRS.
5. Disposal of CRS:
5.1. Officer to Sr. Executive, QC shall discard the expired CRS solution immediately after
expiry.
5.2. Officer to Sr. Executive, QC shall discard the Reference Standard after final use and affix the label of the CRS vial in the CRS logbook after subsequent entry of respective CRS. Officer to Sr. Executive, QC shall record the discard history in the CRS log-book mentioning the quantity discarded.
5.3. Officer to Sr. Executive, QC shall prepare a list of Outdated/Expired reference standard selected for disposal according to Appendix-C and take approval from Department Head or his nominee. Also raise an internal requisition and issue CRS for the discarded amount in IFS software.
5.4. Officer to Sr. Executive, QC shall dispose Outdated/Expired vial one after another under the Fume Hood.
REFERENCES
- British Pharmacopoeia
- United States Pharmacopoeia
- European Pharmacopoeia
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