A reference standard material is defined as highly purified compound that is well characterized by FDA (US Food and Drug Administration) or company or laboratory. Reference standards are highly characterized specimens of drug substances, excipients, reportable impurities, degradation products, compendial reagents, and performance calibrators by USP (US Pharmacopeia). Reference standards are used to determine quantitative data (such as assay and impurity), qualitative data (such as identification test), and calibration (such as melting point standard). Therefore, the quality and purity of the reference standards are crucial to achieve scientifically valid results
FDA: Specifically, prepared drug substance batch and an authentic material of the highest purity used for structural elucidation and benchmark for working standards.
ICH (Q6A): A reference standard from new drug substances intended for assays, its impurities should be adequately identified and/or controlled and purity should be measured by a quantitative procedure.
The US Pharmacopeia (USP) defines reference-standard materials as “highly characterized specimens of drug substances, excipients, reportable impurities, degradation products, compendial reagents, and performance calibrators”
|Laboratory made Reference Standards|
|Company Reference Standards|
|Official Reference Standards|
|Primary Reference Standards|
|Primary Reference Standards|
|Secondary Reference Standards|
|Supplementary Reference Standards|
The reference standards used as the basis for quantitative and qualitative testing. Impurity Reference standards: Not much guidance from authorities here as per ICH Q3A the
Reference standards used in the analytical procedures for control of impurities should be evaluated and characterized according to their intended uses.”
|Type of Reference STD||Uses|
|Assay||To determine potency for active pharmaceutical ingredients (APIs) and salts|
|Degradation Products||To identify and possibly to quantitate degradation products|
|Process Impurities||To identify and possibly quantitate process-related compounds|
|Resolution Standard||To determine assay performance or impurity method|
|Metabolites Standard||To identify and possibly to quantitate substances generated through a metabolic process.|
When pharmacopeial reference standard is not available then it is prepared by synthesizing as per below.
Reference material is selected from a particular batch. After assigning its batch number its characteristic properties are documented for reference purpose and comparison with future production lots.
The material selected as a primary standard should be highly stable, free from water of hydration and bear traceability to a national or international standards body. Besides the qualification results, the batch-specific certificate of analysis also includes details on the recommended storage conditions as well as sample spectra and chromatograms.
The reference standard materials were prepared as per below procedure:
As a part of the qualification of identity and purity standards minimal required tests for initial characterization were typically performed by using the following tests:
Scientists and Experts at Veeprho Laboratories continuously developing and manufacturing the highest purity grade reference standard with complete characterization using various techniques. (HPLC, ICP-MS, GC-FID, NMR, LC–MS, TGA and FTIR).