Preparation of Primary Standards For Non Pharmacopoeial Products

1.0    PURPOSE:

1.1    To lay down the procedure for preparation, standardization and use of primary standards for Non-pharmacopoeial products.

2.0    SCOPE:

2.1    This SOP is applicable for Non-pharmacopoeial products in Quality Control Department.

3.0    RESPONSIBILITY:

3.1    Sr. Executive – QC 

4.0    ACCOUNTABILITY:

4.1    Asst. Manager – QC 

5.0    PROCEDURE:

5.1    Non-pharmacopoeial standards shall be procured from APL, R&D or from any vendor or shall be prepared from any of the plant batch by full characterization.
5.2    Code number shall be allocated as mentioned below for the characterized primary standards.

5.3    Characterization shall be done by using the following relevant techniques for the plant batches to qualify as primary standard.
1)    NMR
2)    MASS
3)    IR
4)    UV
5)    XRD
6)    DSC
7)    Melting Range
8)    Water by KF
9)    Loss on drying
10)    Residue on ignition
11)    Chromatographic purity by HPLC/GC/TLC
12)    Assay by chemical 
13)    Residual solvents by GC

5.4    Purity/potency of primary standard shall be defined as follows by mass balance method.

Defined potency    = Chromatographic purity by HPLC/GC – (Water 
Content/LOD + Residue on ignition + Residual solvents by GC/NMR)

5.5    All primary standard shall be retested after one year from the effective date.  During retesting, only chromatographic purity and Water content/LOD need to be checked.  If there is no significant change* observed during re-testing, the standard validity period can be extended to another one year without applying correction to the potency.  If significant change observed during re-testing, then the potency value should be corrected as per the re-test report and validity period of the primary standard can be extended for another one year.
*No significant change – if the retested results for Water content/LOD falls within the following range in comparison with the previous results and with in the specification.

*No significant change –The retested results for related substances should not be more than ±20% of the previous results, and for Chromatographic purity, not more than ±0.3% of the previous results and with in the specification.

5.6    After retesting, the primary standard number shall be suffixed as ‘A’.

5.6.1    Example: The primary standard of number xxxxx, after retesting will be numbered as ‘xxxxx.

5.7    Storage and distribution:

5.7.1    Primary standards should be preserved in tightly closed amber coloured glass vials, in a closed container and stored in the refrigerator at 2° to 8°C.
5.7.2    The Primary standards shall be distributed into 16 vials.
5.7.3    Primary standard vials shall be labeled as per the Annexure III.
5.7.4    The labeled vials shall be stored in a month wise plastic containers and stored in refrigerator.
5.7.5    Validity period for Primary standards shall be one year from the effective date and the effective date shall be with in one week from the date of completion of analysis.
5.8    List of primary standards shall be mentioned as per the Annexure – IV.

6.0    ANNEXURES:

6.1    Annexure – I: Primary standard protocol
6.2     Annexure – II: Primary standard Profile
6.3    Annexure – III: Primary standard label
6.4    Annexure – IV: List of primary standards
6.5    Annexure –V: Primary standard retesting protocol

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