Reference standards
a. Primary standard is a standard designated or widely acknowledged as having the highest metrological qualities and whose property value is accepted without reference to other standards of the same property or quantity, within a specified context.
b. International standard is a primary standard provided to enable the results of biological or immunological assay procedures to be expressed in the same way throughout the world. The value assignment is in International Units (IU) or another suitable unit. The unitage is normally assigned to a first international standard by the World Health Organization (WHO) in an arbitrary manner based on an international inter laboratory study. Activities in International Units are assigned to replacement international standards, where appropriate, by comparing them with a previous standard
c. Secondary standard is a standard whose property value is assigned by comparison with a primary standard of the same property or quantity
d. European Pharmacopoeia reference standard is a reference standard established under the aegis of and adopted by the European Pharmacopoeia Commission.
e. European Pharmacopoeia chemical reference substance (CRS) is a substance or mixture of substances intended for use as stated in a monograph or general chapter of the European Pharmacopoeia. European Pharmacopoeia biological reference preparation (BRP) , too .
CRSs are in general primary standards, except for those (notably antibiotics) that are calibrated in International Units. The latter are secondary standards traceable to the international standard.
BRPs are either secondary standards calibrated in International Units or primary standards, which may be used to define a European Pharmacopoeia Unit (Ph. Eur. U.). Other assigned contents may also be used, for example, virus titre or number of bacteria
f. European Pharmacopoeia herbal reference standard (HRS) is a herbal drug preparation (usually an extract) or a herbal drug intended for use as stated in a monograph or general chapter of the European Pharmacopoeia.
g. Reference material (RM) is a material sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in the measurement process.
h. Certified reference material (CRM) is a reference material characterised by a metrologically valid procedure for one or more specified properties, accompanied by a certificate that states the value of the specified property, its associated uncertainty, and a statement of metrological traceability.
\ A European Pharmacopoeia reference standard may be suitable to determine the content/potency of that substance in a pharmaceutical preparation provided all of the following conditions are fulfilled:
— the chromatographic assay method described in the active substance monograph is employed; — the applicability of the method to the particular pharmaceutical preparation (absence of interference) is verified by the user;
— any pre-treatment of the sample (e.g. extraction, filtration) is validated for the particular pharmaceutical preparation.
\ It is the policy of the European Pharmacopoeia to supply reference standards in adequate quantities for immediate use after opening of the container.
\ A secondary standard shall exhibit the same property or properties as the primary standard to which it is traceable.
Test programme for primary standards
- Characterisation of the substance by appropriate chemical attributes.
- Determination of purity:
- determination of the content of related substances by an appropriate separation technique and/or spectrometric method, where applicable;
- quantitative determination of water;
- determination of the content of residual solvents;
- determination of loss on drying, which may in certain circumstances replace the determinations of water and residual solvents
- determination of inorganic impurities
- determination of purity by an independent method
\ For chemical reference standards
- identification
- \
\ \ \ \ \ \