FMEA Risk Assessment for Isolator Used in Sterility Testing
1. Scope and Purpose
Scope: To assess the risks associated with the use of an isolator in sterility testing of pharmaceutical products.
Purpose: Identify potential failure modes, their causes and effects, and implement controls to mitigate the risks to acceptable levels in
compliance with regulatory and industry standards.
2. System Description
An isolator for sterility testing is a closed, controlled environment used to perform sterility tests, minimizing contamination risk by physical
separation from the external environment. It includes:
Physical enclosure with HEPA filters
Transfer ports
Glove ports
Air handling and pressure control
Environmental monitoring sensors
Cleaning and decontamination systems
3. FMEA Table
Risk
Process Potential Potential Severit Occurrenc Detectio Priority Existing Recommende
Failure Mode
Step/Component Causes Effects y (S) e (O) n (D) Numbe Controls d Actions
r (RPN)
Implement
Damaged Contamination
Regular seal robust seal
Isolator Physical seals, ingress, false
9 3 4 108 inspections, materials;
enclosure breach/leakage improper positive/negativ
leak testing enhance
closure e sterility result
training
Filter
Implement
clogging, Contaminated Routine filter
Filter failure or redundant
HEPA filters damage, air entering 10 2 3 60 integrity
bypass filtration,
improper isolator testing
increase filter
installation
Risk
Process Potential Potential Severit Occurrenc Detectio Priority Existing Recommende
Failure Mode
Step/Component Causes Effects y (S) e (O) n (D) Numbe Controls d Actions
r (RPN)
replacement
frequency
Use high-
Handling quality gloves;
Operator Visual glove
Glove tears or errors, periodic glove
Glove ports contamination, 9 4 4 144 inspections
punctures material replacement;
exposure risk before use
degradation glove leak
testing
Install UPS for
Equipment Loss of isolator Continuous
Air pressure Pressure loss or power backup;
failure, power sterility 10 2 5 100 monitoring,
control system fluctuation regular system
outage environment alarm systems
maintenance
Improper Automate
Transfer port Contamination SOPs for
Transfer ports transfer 8 3 5 120 transfers where
contamination ingress material
technique, possible;
Risk
Process Potential Potential Severit Occurrenc Detectio Priority Existing Recommende
Failure Mode
Step/Component Causes Effects y (S) e (O) n (D) Numbe Controls d Actions
r (RPN)
port seal transfer, improve seal
failure training design
Automate
Incomplete or Inadequate Validation of sterilant
Decontaminatio ineffective sterilant Microbial sterilization dosing; use
10 3 3 90
n process decontaminatio concentration contamination cycles; process biological
n , contact time monitoring indicators
regularly
Use redundant
Sensor failure Calibration and sensors;
Environmental Sensor drift, Undetected
or inaccurate 9 2 4 72 maintenance implement
monitoring malfunction contamination
readings schedule alarm
escalation
Risk
Process Potential Potential Severit Occurrenc Detectio Priority Existing Recommende
Failure Mode
Step/Component Causes Effects y (S) e (O) n (D) Numbe Controls d Actions
r (RPN)
Implement
Human error Inadequate Contamination, Comprehensiv competency
Operator
during training, incorrect test 8 4 5 160 e training, SOP assessments;
handling
operation fatigue results adherence improve
ergonomics
Regular
Inadequate retraining;
Residue or Cleaning
Cleaning of cleaning False positive improve
contamination 9 3 3 81 validation and
isolator procedure or sterility test cleaning
post-cleaning routine checks
validation validation
protocols
Labeling Barcode Automate
Sample False sterility
errors, systems, SOPs, sample
Sample handling contamination results; product 9 3 4 108
improper double tracking;
or mix-up rejection
handling verification implement
Risk
Process Potential Potential Severit Occurrenc Detectio Priority Existing Recommende
Failure Mode
Step/Component Causes Effects y (S) e (O) n (D) Numbe Controls d Actions
r (RPN)
stronger
controls
4. Risk Evaluation and Classification
Severity (S): 1 (least severe) to 10 (most severe) based on impact on sterility and patient safety.
Occurrence (O): 1 (rare) to 10 (frequent) based on likelihood of failure.
Detection (D): 1 (easy to detect) to 10 (difficult to detect) based on current controls.
Risk Priority Number (RPN) = S × O × D
Acceptable risk thresholds should be defined by the organization, with high RPNs (>100) prioritized for mitigation.
5. Regulatory and Industry Guidelines Referenced
USP <71> Sterility Tests — defines sterility test procedures and environmental controls.
ISO 14644 — Cleanrooms and associated controlled environments.
ISO 14971 — Risk management for medical devices; framework for risk assessment.
FDA Guidance for Sterility Testing — expectations for sterility assurance and contamination control.
EU GMP Annex 1 (Revision 2022) — manufacture of sterile medicinal products; requirements for isolators.
ICH Q9 — Quality Risk Management principles.
ISO 8573 — Compressed air quality (for isolator air supply).
6. Summary of Key Risks
Risk Impact Mitigation Priority
Contamination ingress Leads to false sterility results, patient risk High
Glove breach Operator contamination or exposure risk High
Decontamination failure Persistence of viable microorganisms High
Pressure control failure Loss of aseptic environment High
Human errors Compromise of sterility test validity High
7. Recommendations for Risk Mitigation
Implement robust training programs for operators with regular competency assessments.
Use validated cleaning and decontamination protocols with frequent monitoring and revalidation.
Employ automated environmental monitoring with redundant sensors and alarm escalation.
Maintain a strict preventive maintenance schedule for all isolator components.
Incorporate automated or semi-automated material/sample transfer systems to reduce human error.
Use high-quality consumables (gloves, filters) and verify integrity prior to use.
Conduct periodic risk review and updates to FMEA as new data or technologies become available.
