Selection, Application and preparation standards for Pharma

Assoc Prof. Vorasit Vongsutilers, Ph.D., R.Ph. Assist Prof. Bodin Tuesuwan, Ph.D., R.Ph.
Department of Food and Pharmaceutical Chemistry,
Faculty of Pharmaceutical Sciences, Chulalongkorn University
Reference Standards
Primary chemical reference substance
… is widely acknowledged tohave the
appropriate qualities within a
specifiedcontext, andwhoseassigned
content when used as an assay
standard is accepted without
requiring comparison with another
chemical substance.
WHO general guidelines for the establishment, maintenance and distribution of
chemical reference substances - TRS 943 - Annex 3
Annex 3, WHO Technical Report Series 943, 2007
Secondary chemical reference substance
A secondary chemical reference
substance is a substance whose
characteristics are assigned
and/or calibrated by comparison
withaprimary chemical reference
substance.
WHO general guidelines for the establishment, maintenance and distribution of
chemical reference substances - TRS 943 - Annex 3
Annex 3, WHO Technical Report Series 943, 2007
Reference Material

material, sufficiently homogeneous and

stable with respect to one or more
specified properties, which has been
established tobe fit for its intended use in
ameasurement process
ISO17034:2016
Certified Reference Material
CRM
reference material characterized by a
metrologically valid procedure for one or more
specified properties, accompanied by a reference
material certificate that provides the value of the
specifiedproperty, itsassociated uncertainty, and
astatement of metrological traceability
ISO17034:2016
USP RS
… to have the appropriate qualities to support their intended use

USP RS also assume official status and legal recognition in the

UnitedStatesandother jurisdictionsthat recognizethe USP or NF
(see General Notices, 2.30Legal Recognition).

Where USPor NF tests or assays call for the use of a USPRS,

only those results obtained using the specified USPRSare conclusive
BP 2021
PRIMARY STANDARDS
Characterisationof the substance
NMR IR

Determination of purity:
Determination of the content of related substances
Quantitative determination of water
Determination of inorganic impurities
Determination of the content of residual solvents
Determination of purity by an independent method (Determination of loss on drying)

BP 2021
… should exhibit the same property or properties as the primary standard,
relevant for the test(s) for which it is established.
The extent of testing may not be as comprehensive as is required for the establishment
of a primary standard.
The secondary standard is established by comparison with the
primary standard to which it is traceable. An official primary standard
is used wherever possible for establishment of secondary standards

BP 2021
A secondary chemical reference substance is a substance whose
characteristics are assigned and/or calibrated by comparison with a
primary chemical reference substance. The extent of characterization and
testing of a secondary chemical reference substance may be lessthan for
a primary chemical reference substance. Although this definition may
apply inter alia tosome substancestermed “WORKINGSTANDARDS”,
part B of these guidelines is intended to apply to secondary reference
substances supplied as “official”, e.g. regional/national standards, and not
tomanufacturers’ orotherlaboratories’ workingstandards.
WHO general guidelines for the establishment, maintenance and distribution of
chemical reference substances - TRS 943 - Annex 3
Annex 3, WHO Technical Report Series 943, 2007
 Obtainsourcematerial
Testingtoestablishtheassignedcontent
(validanalytical method, traceability)
Packaging
PRIMARY Retestingprogram
SECONDARY
STANDARDS STANDARDS
Case: Standardize with API assay
Case: Retest date = API shelf-life or magic number X year
Case: Use of cheaper form for RS
MOLECULE A . Dicyclohexylamine
25mg USD 458

MOLECULE A . Sodium
400mg USD 120
Case: Switching between BPCRS and USP RS
Case:Use of AR grade for RS
Case: ”intended use”