Understanding the Difference Between Working Standards and Reference Standards in Biopharma
What Are Reference Standards?
Reference standards, also known as primary standards, are highly characterized, pure compounds that serve as the benchmark for analytical testing. These standards are typically obtained from recognized regulatory agencies, such as:
- United States Pharmacopeia (USP)
- European Pharmacopoeia (EP)
- National Institute of Standards and Technology (NIST)
- World Health Organization (WHO)
Reference standards undergo extensive characterization and validation to ensure their suitability for analytical testing. Since they represent the highest level of accuracy, they are used for:
✅ Method validation
✅ Instrument calibration
✅ Quality control testing
✅ Stability studies
However, due to their high cost and limited availability, reference standards are often reserved for critical analyses rather than routine laboratory use.
What Are Working Standards?
Working standards, also known as secondary standards, are derived from reference standards and used for routine testing and quality control. A working reference standard (WRS) is qualified against a primary reference standard to ensure accuracy and reliability.
Working standards are used for:
✅ Routine batch testing
✅ In-process control measurements
✅ Daily calibration of analytical instruments
Since working standards are qualified but not as rigorously characterized as reference standards, they are more cost-effective and practical for day-to-day laboratory use.
Key Differences Between Reference Standards and Working Standards
| Feature | Reference Standard | Working Standard |
|---|---|---|
| Source | Regulatory agencies (USP, EP, NIST, WHO) | Derived from reference standard |
| Characterization | Extensively validated and certified | Qualified against reference standard |
| Cost | High | Lower |
| Usage | Method validation, regulatory compliance, calibration | Routine testing, in-process control |
| Availability | Limited | Readily available |
Why Qualification of Working Standards is Critical
Since working standards are used more frequently, proper qualification protocols must be followed to ensure they remain accurate and reliable. This process includes:
✔️ Comparative testing against the reference standard
✔️ Stability assessments to confirm consistency over time
✔️ Regular requalification to maintain accuracy
By establishing a well-defined working reference standard (WRS) program, pharmaceutical companies can maintain data integrity, improve operational efficiency, and ensure regulatory compliance.
Conclusion
Understanding the difference between reference standards and working standards is crucial for maintaining high-quality pharmaceutical products. While reference standards provide the highest level of accuracy, working standards allow for efficient and cost-effective routine testing. Proper qualification and maintenance of working standards ensure continued accuracy and compliance with industry regulations.
At BioPharma Consulting Group, we specialize in quality control solutions to help companies establish effective reference and working standard protocols. Contact us today to learn how we can support your analytical testing and compliance needs.
Article by:
Christopher M. LeBlanc
Founder & Principal Consultant
Christopher LeBlanc is the founder and Principal Consultant of BioPharma Consulting Group, LLC, a patient passionate, innovative consulting agency that provides quality services to the Biotechnology, Pharmaceutical and Gene Therapy industries.
Biotech & Pharmaceutical Consulting Services
Quality Control
Quality Assurance
Our Quality Assurance services focus on improving quality, integrity and compliance by providing certainty of the product and data. Guaranteeing effectiveness and efficiency as per client expectations and regulatory requirements with regard to patient safety.
Project Management
BCG will manage client projects with technical competencies focused on quality design efficiency through customized strategies to meet all company goals and produce completed projects compliant to objectives and timelines.