Creating Working Reference Standard (WRS) Qualification Protocols

Approved and ready to use WRS qualification protocols significantly reduce workload, time and resources when transitioning from one WRS lot to another.

Primary reference standards (PRS), secondary reference standards and working reference standards (WRS) are established to ensure quality in pharmaceutical manufacturing, development, quality assurance and quality control laboratories. Reference standards must be maintained with assurance in their accuracy, precision and stability attributes for extended periods of time.

In most cases, Pharma/Biotech companies need to qualify their own working reference standards (WRS) from proprietary final drug substance and/or drug product. However, many organizations are not familiar with the requirements needed for selecting and qualifying reference standards for routine use as the industry lacks guidance, literature and information provided by FDA, ICH, Eudralex etc. can be difficult to understand and follow.

Clients typically create WRS qualification protocols and reports every time a new WRS lot is implemented for routine use. These protocols and reports often lack compliance.

At BioPharma Consulting Group (BCG) we assist our clients by creating product specific WRS protocols, eliminating the need to generate protocols for each WRS lot of the same product. BCG has obtained the necessary WRS qualification expertise for creating compliant protocols by leveraging information from industry leading professionals including ex-FDA consultants and colleagues. Providing this information directly to clients significantly reduces time and resources needed for research on reference standard qualification guidance and for creating, reviewing and approving protocols.

The following are key components to consider when selecting and qualifying a new lot of WRS for routine use:

1. Bulk Drug Substance/Product Release:

• Establish protocols with appropriate methods and testing, including characterization testing.
• Aliquoting
• Content Uniformity
• Generate CoA’s.

2. WRS Qualification vs PRS (Comparability):

• Establish protocols with appropriate methods and testing, including characterization testing.
• Generate comparability reports.

3. Annual Stability:

• Establish protocols with appropriate methods and testing.
• Determine the total number of years for the stability program.
• Generate stability reports.

4. Report Generation:

• Determine the necessary content to be included in the qualification report.

Over the past 25 years, BioPharma Consulting Group agents have worked with many companies by providing industry guidance and expertise for handling reference standards including selection, qualification, testing plans, labeling, storage and stability monitoring programs. It is never too late to ensure your reference standard qualification procedures, protocols and reports contain the current regulatory guidance needed for routine use.