This document discusses the handling of reference standards. It defines reference standards as certified, uniform materials intended for use in specified tests to compare the properties of test samples. Reference standards are classified as primary, set by pharmacopoeial authorities, secondary, calibrated by primary standards, or in-house standards made for routine laboratory work. Proper storage is important to maintain the quality and stability of reference standards over time in the recommended conditions away from heat, light, and humidity. Certificates of analysis provide information on the reference standard including tests conducted and intended use. Good practices for handling include using appropriate personal protective equipment and properly labeling, checking certificates and purity, and storing in a sealed and protected environment.

1. HANDLING OF
REFERENCE STANDARDS
LIM WEN JUN
PRODUCT AND COSMETIC TESTING SECTION

2. Outline
1 Definition
2 Classification
3
Establishments – CoA, Validity,
Storage Condition & Safe Handling
4 Case Study
Lovastatin in Chemical Analysis Unit (Traditional & Cosmetic)

3. Reference Standard = Reference Substance = Reference Material
• A certified, uniform / homogenous material that is intended for use
in specified tests;
• Possesses a degree of purity adequate for its intended use.
• Its properties are compared with those product under
examination (i.e. test sample)
REFERENCE STANDARDS ??

4. CLASSIFICATION
OF REFERENCE STANDARDS
Primary
RS
Secondary
RS
In-house reference
standards

5. Primary Reference Standard
• Pharmacopeial Reference Substance
• Internationally accepted as having appropriate qualities within a specified
context and whose value is accepted without reliance on comparison to
other reference material.
• Established and distributed by pharmacopoeial authorities following the
general principles of ISO Guide 34 for Reference Material Producers
(RMP).
• Pharmacopoeial authorities e.g. USP, BP, EP
CLASSIFICATION

6. Secondary Reference Standard
• Working Standard
• Substance whose characteristics are assigned and/or calibrated by
comparison with a primary standard
• The extent of characterization and testing may be less extensive.
• Traceable to primary standard
• ASEAN RS, Sigma-Aldrich etc
CLASSIFICATION

7. In House Reference Standard
• Reference standard that was manufactured, purified and fully
characterized and structurally elucidated.
• Use for routine laboratory work, in the analysis of production batches of
new drug substance or drug products (NCE).
CLASSIFICATION

8. Applications
Quantitative Tests
• Assay
• Impurity Tests
Qualitative Tests
• Identification Tests
Equipment Calibrations

9. Certificate of Analysis
 Name of reference substance
 Batch / control number
 Description of the physical nature of the reference substance
 Tests carried out together with the results
 Intended use of the reference substance
 Direction for use (e.g. instruction on drying before use)
 Recommended storage conditions

10. Certificate of Analysis

14. Certificate

16. Validity
• Quality & Stability over time
• ALWAYS check BEFORE using

17.  Follow recommended storage condition
 Avoid high temperatures
 Avoid light
• Amber glass
 Prevent contamination
 Avoid humidity
• Store in dry location such as a desiccator
Good Practices for Storage

19. Why proper storage?

20.  Good Practices for personnel protection
 Wear appropriate Personal Protective Equipment (PPE):
 Gloves,respirator,etc
 Long sleeves or lab coat
 Closed-toe shoes
 Check handling precautions for specific compounds (MSDS)
 Check label properly
 Check CoA and purity
 Store in proper environment and seal with parafilm
Proper Handling

21. Handling of Lovastatin RS
In Traditional & Cosmetic Subunit

22. TRC
USP

23. Thank you