Usage of Reference
Standard Working Standard the Complete Guidelines
Reference standards are authentic substances
approved by the reference standard approving authority as a preferred method
for use. Comparison Standards are described as individual monographs and
methods of analysis. The purpose of this is to define the procedure for
preparation, standardization, and usage of a working standard.
Wherever possible this reference standard shall
be used including those for which impurities are not available. Remember the
same can be gotten from chemical research laboratories, drug substance
manufacturers, a contract giver or an in-house references standard at the
There are certain precautions that have to be
taken like using a clean and dry amber coloured vial for storage of working
standards. All reference standards
or impurity standards have to be stored as per the storage condition mentioned
in MSDS from the supplier. Remember before usage, the temperature of the vials
must reach room temperature. In the case that potency of the working
standard is found more than 100.0%
during the standardization, as a policy cut off the potency of the working
standard will be considered as 100.0%.
of Reference Standard
According to pharmaceutical standards, reference
substances or standards are authentic purified chemicals supplied by the
official pharmacopoeia commission. These are
generally used for comparison to determine the purity of the test specimen. In
case the reference standard isn’t available in the pharmacopeial catalog, the
manufacturer shall be asked for their reference standard or working standard
with a certificate of analysis. As reference standards are usually available
only in small quantities, working standards can be prepared to act as a
substitute, these are prepared from approved raw materials and validated
against authentic reference standards or substances.
All standardized records of working standards
shall be maintained in a QC laboratory. The Inventory and consumption of
reference standards shall be maintained as per Annexure – VI, the validity of
reference standards shall be verified on a quarterly basis, and before
preparation for a working standard.
Now, in case the reference standard is found to
be consumed or expired during verification, then the indent for procurement of
a fresh lot shall be initiated by the Manager Q.C.
of Working Standard
Select any approved batch, the quality
attributes of the selected batch will be reviewed critically with special emphasis on its
assay and related substances. This batch shall have reviewed according to pharmaceutical
standards and the selected batch
shall have maximum assay/purity and the lowest related substance.
Analyse the selected batch against the reference
standard using logbook as per Annexure – VI and follow the stipulated control
procedure which includes Description, Identification, Moisture Content, Assay,
Perform Assay, and Moisture Content Analysis in triplicate. The QC manager shall allocate the material
abbreviation and assign a unique number to each working standard as below.
WS – denotes the working standard
‘/ ‘- denotes the slash
XXXX – denotes the four-letter abbreviation for
YY – denotes the year of preparation of working
01 – denotes the serial number of working
A typical example of Paracetamol working
standard shall be as below:
The details of results in the record analysis
sheet are to be entered and calculated with the purity of the working standard,
post which it is to be transferred to clean amber coloured vials, sealed and
labelled as per Annexure – V. Fifteen vials of 2gm should be prepared and
another 20gm working standard should be stored in the vial. Prepare a list of
working standards to identify the due date for preparation and in case of any
absence of API or CRS working standards received from the manufacturer should
be used for respective analysis.
and Expiry Working Standards
All working standards are to be stored under
refrigeration, in case a specific storage
condition is mentioned then the material should be stored according to that.
All working standards shall be brought to ambient temperature before use and
the details to be recorded in the usage log book as per Annexure – I. The
expiry period for the working standard is one year from the day or preparation,
and for a vial is one month, expiry period should not exceed the retest period
of the selected API batch.
Expired working or reference standards should
not be used. Instead, they should be discarded immediately in a proper way.