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PDA-Aligned Validation: Feature-Tec Advancing Sterile Filtration
2026-02-02
In the biopharmaceutical industry, sterile filtration has always been a critical element of aseptic assurance. With the continuous evolution of regulatory expectations, the Parenteral Drug Association (PDA) released a major update to Technical Report No. 26 (TR 26) in 2025. This revision marks a fundamental shift in sterile filtration practices—from a focus on compliance-based verification to a more advanced paradigm of quality risk management.
By comparing the earlier and revised versions of PDA TR 26, this article outlines the key developments in sterile filtration validation and provides practical guidance to help pharmaceutical manufacturers proactively respond to regulatory upgrades.
More Precise Definitions:
From “Generic Concepts” to a Clear Definition of “Sterilizing Grade”
2008 Edition
“A filter that reproducibly removes test microorganisms from the process stream, producing a sterile filtrate.”
2025 Revised Edition
“For sterilizing filters specifically, a consensus has arisen in the industry to define sterilizing-grade filters not by physical pore size measurement, but by its ability to reproducibly retain 10⁷ CFU per cm² of Brevundimonas diminuta according to the ASTM F838 standard.”
This revision not only clearly defines the performance threshold of sterilizing-grade filters but also reflects regulators’ increasingly refined expectations for high-risk process equipment.
A Clear “Three-Layer Validation Model” for Sterile Filtration Compliance
1. Outer Layer: Rated Filters
Filters labeled only with a nominal pore size (e.g., 0.22 μm or smaller) represent basic physical specifications and do not constitute validated sterilizing performance.
2. Middle Layer: Sterilizing-Grade Filters
Sterilizing-grade filters must be supported by ASTM F838 bacterial challenge test data provided by the supplier, demonstrating a ≥7 log reduction value (LRV). This level represents the industry-recognized minimum performance threshold.
3. Inner Layer: Sterilizing Filters (Process-Specific)
Beyond being sterilizing grade, a filter must also undergo process-specific bacterial retention validation under actual manufacturing conditions. This includes consideration of:
- Product characteristics (e.g., viscosity, pH, chemical composition, bioburden)
- Process parameters (e.g., pressure, temperature, contact time)
Practical experience has shown that:
“Passing ASTM F838 in the laboratory does not automatically guarantee sterility in real production.”
Therefore, regulations further emphasize that a “sterilizing filter” must be supported by process-specific validation, accounting for chemical compatibility, process variability, and their impact on bacterial retention. This approach ensures end-to-end sterility assurance rather than isolated test compliance.
Responsibility for this validation lies with the drug manufacturer. According to relevant sterile filtration guidelines, such studies are commonly conducted by qualified testing organizations, including filter manufacturers or independent third-party laboratories.
Regulatory Trend Analysis
1. Risk-Based Control
Sterile filtration is no longer treated as a single, generalized concept. Instead, it is managed as a layered, stage-based validation system, enabling comprehensive risk control from nominal specifications to process suitability.
Validation strategies are shifting from experience-driven to science- and risk-based approaches, requiring systematic evaluation of the interactions between product, process, and filter.
2. Clear Accountability Boundaries
- Filter suppliers are responsible for providing sterilizing-grade filters supported by ASTM F838 data.
- Drug manufacturers are responsible for process-specific validation.
Together, this establishes a closed-loop accountability model spanning the supply chain and manufacturing operations.
3. Global Regulatory Convergence
Similar layered requirements are reflected in EMA GMP Annex 1, FDA guidance, and NMPA aseptic processing regulations, indicating an ongoing trend toward global regulatory harmonization.
Key Recommendations for Pharmaceutical Manufacturers
In response to the enhanced requirements of PDA TR 26 (2025), companies are advised to:
- Implement layered validation management, clearly distinguishing supplier data from in-house process validation responsibilities.
- Conduct early-stage risk assessments, using tools such as FMEA to identify critical control points in filtration processes.
- Strengthen collaboration with filter suppliers and communicate process-specific requirements at an early stage.
Conclusion
The release of PDA TR 26 (2025) represents not only an update of technical requirements, but also a fundamental evolution in quality management philosophy. It encourages pharmaceutical manufacturers to transition from passive compliance to proactive risk control, building a comprehensive sterile filtration assurance system across the entire process chain.
For pharmaceutical companies, a thorough understanding and effective implementation of these requirements are essential to improving product quality, safeguarding patient safety, and meeting global regulatory expectations.
This article is based on the interpretation of PDA Technical Report No. 26 (Revised 2025): Sterilizing Filtration of Liquids and is provided for reference only. Actual implementation should be aligned with specific process conditions and applicable regulatory requirements.
In the next installment, we will provide an in-depth analysis of validation updates. Stay tuned to Feature-Tec Life Sciences. For further information on sterile filtration validation strategies or product support, please contact Feature-Tec for consultation.
About Feature-Tec
Feature-Tec has over 20 years of experience in the fields of filtration, separation, and purification, integrating R&D, manufacturing, and testing & validation capabilities. Its solutions serve a wide range of industries, including semiconductors, FPD, biopharmaceuticals, nuclear power, lithium batteries, automotive, food & beverage, petrochemicals, water treatment, machinery & equipment manufacturing, marine engineering, and renewable energy.
Feature-Tec provides fully automated filtration systems covering filter elements, separation equipment, ceramic membrane filtration, magnetic filtration, and backwash filtration. Its successful applications include catalyst recovery filtration, Raney nickel magnetic filtration, nanomaterial slurry concentration and washing, amine desulfurization filtration, activated carbon decolorization, silicon steel pickling, reinjection water filtration, comprehensive dust control, and sulfuric acid concentration, among many other innovative filtration processes.
With a global footprint and professional testing capabilities certified to CNAS / ISO 17025 and GMP-like standards, Feature-Tec offers services including cleaning validation, contaminant analysis, extractables and leachable studies, bacterial retention process validation, chemical compatibility studies, safety assessments, adsorption evaluations, and filtration efficiency testing.
We welcome you to contact Feature-Tec for customized high-efficiency filtration solutions and to jointly advance a more sustainable future.
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