1️⃣ Why Foreign Fibres are Critical
- Sterile injectable products must be free from visible contamination.
- Even a single foreign fibre is considered critical contamination, because:
- It can act as a nucleation point for microbial growth.
- It may induce immunogenic reactions.
- It represents a breakdown in aseptic control.
- Regulatory agencies (FDA, EMA) expect zero tolerance for visible foreign matter in injectables.
References:
- USP <790> “Visible Particulates in Injections”
- EMA Annex 1 “Manufacture of Sterile Medicinal Products”
- 21 CFR 211.92 “Inspection of Containers”
2️⃣ Potential Origins of Fibres in Sterile Production
In theory, fibres can come from multiple sources in the process:
Personnel and Garments
- Shedding of lint from coveralls, sleeves, cuffs.
- Hair or fibers from undershirts.
- Ineffective gowning or poor garment quality.
Equipment and Tools
- Degradation of gaskets, O-rings, seals.
- Brushes or cleaning tools with synthetic bristles.
- Conveyor belts or air hoses shedding particles.
Materials
- Cardboard shippers shedding cellulose fibres.
- Primary packaging (e.g., stoppers) with embedded lint.
- Labels or paper used in the area.
Environment
- HEPA filter leakage or damage.
- Airflow disturbances causing re-suspension.
- Poor housekeeping accumulating dust and lint.
Process Flow and Methods
- Inadequate cleaning validation.
- Poorly designed material flow—uncontrolled opening of packaging.
- Use of non-dedicated tools without cleaning.
3️⃣ Regulatory Expectations
Regulators require:
- Visual Inspection Programs—100% inspection of parenterals.
- Identification and classification of particulate matter.
- Root cause analysis for any detected contamination.
- Robust CAPA to prevent recurrence.
- Traceability—documentation of every lot and inspection result.
Relevant guidelines:
- USP <790>: Acceptance criteria for visible particles.
- EU GMP Annex 1: Contamination Control Strategy.
- FDA Guidance: Sterile Drug Products Produced by Aseptic Processing.
4️⃣ Identification and Investigation Theory
When fibres are detected, a structured approach is recommended:
Step 1 – Immediate Actions
- Quarantine suspect batches.
- Review in-process controls and environmental monitoring.
Step 2 – Characterisation
- Visual examination (microscope).
- Microscopic measurement (length, diameter).
- Chemical analysis (FTIR, Raman spectroscopy).
- Comparison to known reference samples (garments, filters).
Step 3 – Mapping Possible Sources
- Use of Fishbone (Ishikawa) Diagrams.
- Process mapping to see where ingress could occur.
- Environmental monitoring data review.
Step 4 – Risk Assessment
- Evaluate impact on product quality and patient safety.
- Classify severity and recurrence potential.
Step 5 – Documentation and CAPA
- All findings must be documented in a deviation report.
- Actions tracked through the CAPA system.
5️⃣ Control and Prevention Strategy (Theoretical Basis)
Fundamental Principles:
- Contamination Control Strategy (CCS): Holistic approach covering facility design, process, personnel, materials, equipment, and monitoring.
- Risk-Based Thinking: Prioritising controls based on criticality and contamination potential.
- Lifecycle Approach: Design, qualification, monitoring, and continual improvement.
- Barrier Technologies: Use of Restricted Access Barrier Systems (RABS) or isolators to minimise exposure.
Prevention Tactics:
- Use lint-free, sterile garments.
- Implement dedicated cleaning tools (validated low-shedding).
- Enforce airlock discipline.
- Regularly replace gaskets and seals.
- Maintain robust environmental monitoring.
- Educate personnel on contamination risks and practices.
Risk-Assessment-for-White-Fibres-observed-in-Vial-or-Ampoules
