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OPTIMUS GENERICS LTD. JADCHERLA
(Subsidiary Unit of Glochem Industries ltd.)
TITLE
REFERENCE STANDARDS AND WORKING STANDARDS MANAGEMENT
This note on reference standards and working standards management is intended to address all the elements pertaining to
qualification of reference and working standards that are used during analysis of all products such as Active Pharmaceutical
Ingredients, Impurities, Intermediates, Starting materials etc.
APIs (Pharmacopoeial products)
For all pharmacopeial products, reference standards must be procured from official source, instead of using a characterized inhouse reference standard, as these are used for quantification purpose to establish a working standard.
Reference standard
Source
Qualification process
From any officially
recognized sources
(EP, USP etc)
Re-qualification period
Valid until the date
provided by
Not required
Working standard
pharmacopeia when a
new lot is released
Qualification process
Re-qualification period
Material having more than
99.0% purity or within the
Validity :
specification, whichever is
stringent shall be selected to 2 years
qualify as working standard. (Refer Note-2)
Complete analysis as per
existing STP with the current
lot of reference standard
with multiple assay
preparations
Retest :
1 year (or)
When the new tests
are included / test
methods are revised
(Refer Note-3)
(Refer Note-1)
APIs (Non-Pharmacopoeial products)
Reference standard
Source
Qualification process
Re-qualification period
Working standard
Qualification process
Re-qualification period
If sufficient quantity is available, this reference
standard can be used as working standard. If not,
follow the below procedure
1. From the approved lot
2. R&D purification of
existing approved lot
3. From the technology
transferor
4. From any other
resources
5. From the API
manufacturer
Complete analysis as per Validity :
existing STP
2 years
(Refer Note-5)
Characterization study
HNMR, CNMR, MS,
Retest :
Elemental analysis, IR. If When the new tests
applicable, XRD, TGA,
are included / test
DSC
methods are revised
(Refer Note-4)
Material having more than
99.0% purity shall be
selected as working
standard.
Complete analysis as per
existing STP with the
current lot of reference
standard with multiple
assay preparations
Validity :
2 years
(Refer Note-2)
Retest :
1 year (or)
When the new tests
are included / test
methods are revised
(Refer Note-3)
(Refer Note-1)
Head Office: GV Chambers, 7-2-C8 & C8/2, Industrial Estate, Sanathnagar, Hyderabad 500 018, AP, India
Page
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OPTIMUS GENERICS LTD. JADCHERLA
(Subsidiary Unit of Glochem Industries ltd.)
TITLE
REFERENCE STANDARDS AND WORKING STANDARDS MANAGEMENT
Standards at finished dosage forms facility
Following table is applicable for API and its impurity standards which are used at finished dosage forms facility
Reference standard
Source
Qualification process
Re-qualification period
Working standard
Qualification process
Re-qualification period
Validity :
As provided by the API
be obtained from the API manufacturer
manufacturer with
traceability to the fully
Retest :
characterized reference
Not required.
standard
Working standard shall
From API manufacturer
No need to procure
Not applicable
(No additional
qualification is required
at in-house)
Request API
manufacturer to send
the retest CoA before
the retest period is over
Notes:
1.
Once a working standard is established in comparison to a reference standard, further lots of working standards (for next
years) can be established based on the previous working standards. No need to qualify every lot of working standard in
comparison to a reference standard as the previous working standard has been qualified w.r.t. the reference standard.
(CoA shall indicate reference of both these working standard and reference standard)
2.
If the quantity and supporting stability is available, same working standard can be continued for next year also by retesting
for all tests.
This working standard is valid for 24 months even if the reference standard, which is used for qualification of this WS is
expired / invalid in this 24 months period.
3.
During retest, if there is any significant change is observed from initial qualification results, a new working standard to
be qualified.
4.
In any case, if the characterization data is provided along with the standard, no need to perform the study at inhouse again. Working standard can be qualified directly from the same standard.
5.
After 2 years, once the reference standard is expired and no new lot is available at that time, a standard can be prepared
and same can be qualified against the current working standard then characterization study to be completed to qualify as
reference standard. This note is applicable for Pharmacopeial reference standards also.
Head Office: GV Chambers, 7-2-C8 & C8/2, Industrial Estate, Sanathnagar, Hyderabad 500 018, AP, India
Page
3 of 4
OPTIMUS GENERICS LTD. JADCHERLA
(Subsidiary Unit of Glochem Industries ltd.)
TITLE
REFERENCE STANDARDS AND WORKING STANDARDS MANAGEMENT
API impurities (Pharmacopeial products)
If it is possible to synthesize the impurity standards at in-house, no need to procure the reference standards from officially
recognized sources (EP, USP etc.) as these are used for peak identification / system suitability purpose only.
Reference standard
Source
Qualification process
From any officially
recognized sources
(EP, USP etc)
(if not possible to
synthesize in-house)
Re-qualification period
Valid until the date
provided by
pharmacopeia when a
new lot is released
Not required
Working standard
Qualification process Re-qualification period
Not applicable
Not applicable
Not applicable
Not applicable
(Refer Note-6)
1. From in-house
synthesis
2. From the technology
transferor
3. From any other
resources
Validity :
4 years
Characterization study i.e.
HNMR, CNMR, MS,
Elemental analysis, IR
(Refer Note-4)
Retest :
1 year (for purity and
identification)
(Refer Note-3)
Note-6: If there is no availability of respective impurity at relevant official resource and if not possible to synthesize at in-house,
this can be procured from any other officially recognized resources.
(E.g. If impurity-A in Raloxifene HCl is not available at EP and it is not possible to synthesize in-house, this can be procured from
USP, which is Impurity-I. Same can be used for both EP and USP analysis.)
API impurities (Non-Pharmacopeial products)
Reference standard
Source
Qualification process
1. From in-house
synthesis
2. From the technology
transferor
3. From any other
resources
Re-qualification period
Working standard
Qualification process Re-qualification period
Validity :
4 years
Characterization study i.e.
HNMR, CNMR, MS,
Elemental analysis, IR
(Refer Note-4)
Retest :
1 year (for purity and
identification)
Not applicable
Not applicable
(Refer Note-3)
Head Office: GV Chambers, 7-2-C8 & C8/2, Industrial Estate, Sanathnagar, Hyderabad 500 018, AP, India
Page
4 of 4
OPTIMUS GENERICS LTD. JADCHERLA
(Subsidiary Unit of Glochem Industries ltd.)
TITLE
REFERENCE STANDARDS AND WORKING STANDARDS MANAGEMENT
Intermediates and its impurities, API starting materials and its impurities, Other raw materials
No reference standards are required for all these standards. Working standards shall be established and can be used for regular
analysis directly
Material
Source
•
•
Intermediates
•
•
•
•
API starting materials
•
•
Intermediate and API •
staring material
•
Impurities
•
•
•
Other raw materials
and solvents
•
•
Reference standard
Qualification process
Re-qualification period
From the approved lot
R&D purification of existing
approved lot
From technology transferor
From any other resources
Complete analysis as per existing STP
with the current lot of working
standard
Validity : 1 year
From the approved lot
R&D purification of existing
approved lot
From technology transferor
From any other resources
Complete analysis as per existing STP
with the current lot of working
standard
Validity : 1 year
From in-house R&D synthesis
From technology transferor
From any standard resources
Testing for purity and identification
Validity : 1 year
From the approved lot
R&D purification of existing
approved lot
From technology transferor
From any other resources such as
AR grade, LR grade etc.
Complete analysis as per existing STP
with the current lot of working
standard
Validity : 1 year
Head Office: GV Chambers, 7-2-C8 & C8/2, Industrial Estate, Sanathnagar, Hyderabad 500 018, AP, India