Pharmaceutical Reference Standards| How to Manage

Introduction and outcome: Pharmaceutical Reference Standards

Pharmaceutical Reference Standards play a vital role in maintaining pharmaceuticals’ quality, safety and efficacy at every stage during drug development. In this article, you will learn pharmaceutical reference standards, their types, pharmacopeial standards, applications, advantages and source with FAQs.

What are the Pharmaceutical Reference Standards?

Pharmaceutical Reference Standards (PRS) are highly pure materials used in pharmaceutical testing and analysis to ensure the quality of pharmaceuticals (such as raw materials, intermediates and APIs) and dosages forms.

Three Types of Pharmaceutical Reference Standards

The following are the different types of pharmaceutical standards:

Primary Reference Standards
Secondary Working Standards
Calibrators

Primary Reference Standards

These are the highest-pure reference materials that have been characterized in terms of their purity, structure-identity, and potency. They are often prepared and characterised by in-house or purchased from pharmacopoeias such as the United States Pharmacopeia (USP) or the European Pharmacopoeia (EP). Primary standards are used to establish the exact potency of a substance and are often the source material for preparing secondary standards.

Secondary Working Standards

These are standards used in day-to-day laboratory testing. They are often made from secondary working standards and are used in routine quality control (QC) tests for manufacturing processes. Working standards must be regularly checked against primary reference standards for accuracy.

Calibrators

These are specific reference materials used to calibrate measuring instruments, such as spectrometers, chromatographs, and titration systems, ensuring that these instruments give accurate readings.

Related Article: Potency, Purity and assay

What is the difference between Primary reference standards PRS) and Secondary working/reference standards ?

In pharmaceutical analysis, reference standards play a vital role in analytical testing such as identification, assay, purity, impurity profile etc. The following are the difference between primary and secondary reference standards:

Primary Reference Standards:
- These are highly purified pharmaceuticals that have been characterized using different analytical techniques.
- They are often obtained from official sources like pharmacopoeias (e.g., USP, EP) or government agencies.
- Primary standards are considered “official” and serve as the basis for calibration in analytical methods.
Secondary Reference/Working Standards:
- These are substances that are derived from primary reference standards or have been calibrated against primary standards.
- While they are used in routine testing, they may not be as highly characterized as primary standards, and their purity or concentration is determined indirectly by comparison to a primary standard.
- Secondary standards are typically prepared and used in a specific laboratory or manufacturing setting.

In summary, primary reference standards are the characterized standard using different analytical techniques, while secondary reference standards are calibrated against those primary standards for more routine use.

Applications of Pharmaceutical Reference Standards

The following are the different applications of the pharmaceutical standards:

Identity Testing: To confirm the identity of a drug or its ingredients.
Assay Testing: To verify that the active ingredient is present in the correct quantity and meets the specifications.
Impurity Profiling: To test for the presence of impurities and degradation products in drugs, ensuring that the product is safe for consumption.
Stability Studies: To evaluate the long-term stability of drugs under various environmental conditions (temperature, humidity, etc.).
Method Validation: To validate and standardize laboratory methods, ensuring that they give reliable and reproducible results.
Lot Release Testing: To ensure that each batch of pharmaceutical products meets regulatory standards before it is released to the market.
Instruments Calibration: To calibrate the instruments like HPLC, GC, FTIR, UV, UPLC etc.

Standards Providers

United States Pharmacopeia (USP): Provides official standards for drug substances, dosage forms, and biologics in the United States. USP standards are recognized globally.
European Pharmacopoeia (EP): Sets standards for drugs, excipients, and raw materials used in Europe.
World Health Organization (WHO): Publishes international reference standards for biological medicines and other health products.
National Institute for Biological Standards and Control (NIBSC): Provides reference standards for biological substances and vaccines.
Indian Pharmacopoeias (IP)

Certified Reference Materials, EP Reference Standard and USP Reference Standard:

Certified Reference Materials

Characterised reference standard with certificate is called Certified Reference Materials.

EP Reference Standard

Reference standard of the European Pharmacopoeia source is called EP Reference Standard

USP Reference Standard

The reference standard of the United States Pharmacopeia (USP) source is called USP Reference Standard

Importance of Pharmaceutical Reference Standards

Ensuring Quality and Safety: Reference standards help ensure that pharmaceutical products are of the required quality, free from contaminants, and meet potency specifications.
Regulatory Compliance: Regulatory authorities require that pharmaceutical products meet strict standards, and reference standards are critical in demonstrating compliance with Good Manufacturing Practice (GMP) and other regulations.
Reproducibility and Accuracy: Analytical methods, when validated with reference standards, ensure that results are consistent, reliable, and comparable over time, across laboratories, and in different regions.

Also Read: What is the role of AMD (analytical method development) and AMV (Analytical method validation)in Pharmaceutical development?

Conclusion

In summary, pharmaceutical reference standards are crucial tools in maintaining the quality, efficacy, and safety of pharmaceuticals and their drug products. I hope this article has helped you understand Pharmaceutical Reference Standards (PRS) and its importance in pharmaceutical development.

You may also want to check out other articles on my blog, such as

FAQs

What are the pharmaceutical reference standards?

How to make a reference standard?

Reference standards is prepared using highly pure material. Several tests are performed purity, related substances, water/Loss on drying, NMR, mass, FTIR, UV and Elemental analysis. Potency is calculated and structure is characterised before the use of the standard.

What is the reference standard material qualification?

The reference standard is prepared using highly pure pharmaceuticals.NMR, mass, FTIR etc are performed to characterise the structure of the material and tests like chromatographic purify/ loss on drying or water content is performed to calculate the potency of the reference standard.

What is the secondary standard?

The secondary working standards are qualified using primary reference standard and are used in routine quality control (QC) tests.

What is the qualifier?

The reference standards which are used to calibrate measuring instruments, such as spectrometers (e.g UV, FTIR), HPLC, GC, and titrator are called qualifier.

References

Abbreviations

PRS: Primary reference standard
EP: European pharmacopoeias
USP: United state pharmacopeia