Quote from Chief Pharmacist on January 20, 2026, 4:12 pm

1. FDA Draft Guidance (1999): ANDAs – Blend Uniformity Analysis

This was one of the earliest formal attempts to regulate blend uniformity testing. It laid out specific sampling requirements and acceptance criteria to ensure drug product homogeneity prior to final compression or encapsulation. While it was never finalized, it formed the foundation for subsequent approaches.

Key Highlights:

• Minimum 10 sampling locations.
• Acceptance Criteria: RSD ≤ 5% and 90-110% of target concentration.

https://pqri.org/wp-content/uploads/2015/12/FDADraftGuide.pdf

2. PQRI Recommendations (2002): Stratified Sampling for Blend Uniformity

The Product Quality Research Institute (PQRI) introduced the concept of stratified sampling, which evaluates blend uniformity by analyzing samples from predefined blender locations. This addressed variability concerns and ensured more representative results.

Key Highlights:

• Sampling aligned with defined risk-based locations.
• Emphasis on reducing sampling bias and improving uniformity assessment.

https://pqri.org/wp-content/uploads/2016/04/Final_BUWG_Stratfied_Sampling.pdf

3. FDA Guidance (2003): PAT – A Framework for Innovative Manufacturing

The Process Analytical Technology (PAT) framework revolutionized blend uniformity testing by promoting real-time process monitoring using advanced tools like NIR spectroscopy.

Key Highlights:

• Encourages real-time monitoring for blend uniformity.
• Incorporates Quality by Design (QbD) principles to optimize processes.

https://www.fda.gov/media/71012/download

4. ICH Q12 (2019): Lifecycle Management for Pharmaceuticals

The ICH Q12 guideline focuses on managing post-approval changes while maintaining product quality.

Key Highlights:

• Risk-based assessment for process

5. ISPE Guidance (2018): Blend Uniformity and Content Uniformity Tools

The ISPE provided tools and strategies to harmonize blend and content uniformity practices across the industry. The document integrates risk assessment, sampling strategies, and PAT tools for robust monitoring.

https://ispe.org/initiatives/blend-uniformity-content-uniformity/tools

6. FDA Case Study (2023): Risk-Based Blend Uniformity

In this recent case study, the FDA demonstrated the application of risk-based strategies for blend uniformity assessment. It highlights the use of statistical tools and advanced technologies to ensure process robustness.

Key Highlights:

• Incorporation of modern risk assessment techniques.
• Case-based approach for demonstrating uniformity and process control.

https://www.fda.gov/media/168894/download

These guidelines trace the evolution of blend uniformity testing from rigid analytical testing to risk-based approaches and real-time monitoring, aligning with QbD and continuous process verification.