Aseptic Transfer & Contamination Control Network
GMP Validation Framework | Risk-Based Approach | ISO 14644 Compliance
IQ/OQ/PQ
Validated
Risk Assessment
FMEA/HACCP
Master Plan
Continuous
1. VALIDATION LIFECYCLE
DQ – Design Qualification
- •URS (User Requirements Specification)
- •Functional Specifications (FS)
- •Design Review & FMEA
- •Material Selection (USP Class VI)
- •Engineering drawings approval
IQ – Installation Qualification
- •Equipment installation verification
- •Calibration of instruments (±0.5% accuracy)
- •Utility connections (HVAC, gases, power)
- •Documentation review (manuals, COC)
- •Environmental monitoring points
OQ – Operational Qualification
- •Process parameter challenges (worst-case)
- •Alarm testing & interlocks
- •Pressure decay tests (ISO 14644)
- •Airflow visualization studies
- •Temperature/humidity mapping
PQ – Performance Qualification
- •Media fills (3 consecutive runs)
- •Bioburden monitoring
- •Particulate contamination (ISO Class 5)
- •Process simulation studies
- •Operator qualification (GMP trained)
2. ASEPTIC TRANSFER SYSTEMS
Isolator Technology
- •H₂O₂ vapor bio-decontamination (6-log reduction)
- •HEPA filtration (99.995% @ 0.3μm)
- •Positive pressure differential (>15 Pa)
- •Glove integrity testing (pressure hold)
- •Transfer chamber validation
RABS (Restricted Access Barrier Systems)
- •ISO Class 5 background environment
- •Laminar airflow (0.45 m/s ±20%)
- •Door interlocks & alarms
- •Personnel gowning qualification
- •Smoke studies for airflow pattern
Transfer Procedures
- •Aseptic connection validation
- •Container closure integrity (CCI)
- •Sterile filter integrity (bubble point)
- •Process hold time studies
- •Critical zone protection
3. CONTAMINATION CONTROL STRATEGY
Environmental Monitoring
- •Viable particles (CFU/m³): Grade A <1
- •Non-viable particles: 0.5μm & 5.0μm
- •Surface sampling (contact plates, swabs)
- •Personnel monitoring (finger dabs)
- •Real-time monitoring systems
Cleaning & Disinfection
- •Validated cleaning procedures
- •Sporicidal agents (6-log kill)
- •Residue limits (MACO/MRL)
- •Rotation of disinfectants
- •Clean hold time validation
Microbiological Controls
- •Bioburden limits (action/alert)
- •Endotoxin testing (LAL)
- •Sterility testing (USP <71>)
- •Microbial identification
- •Trend analysis & CAPA
4. CONTINUOUS MONITORING SYSTEMS
Critical Process Parameters
- •Differential pressure (21 CFR Part 11)
- •Temperature & relative humidity
- •Airflow velocity & direction
- •HEPA filter integrity (DOP/PAO test)
- •Real-time viable monitoring
Data Integrity (ALCOA+)
- •Attributable, Legible, Contemporaneous
- •Original, Accurate, Complete
- •Consistent, Enduring, Available
- •Electronic signatures (21 CFR Part 11)
- •Audit trail requirements
5. RISK ASSESSMENT & MASTER PLAN
Risk Assessment Tools
- •FMEA (Failure Mode Effects Analysis)
- •HACCP (Hazard Analysis Critical Control)
- •Risk Priority Number (RPN) calculation
- •Severity × Probability × Detection
- •Risk mitigation strategies
Validation Master Plan
- •Scope & objectives definition
- •Organizational responsibilities
- •Validation strategy & approach
- •Documentation requirements
- •Change control procedures
- •Revalidation schedules
- •Annual product review integration
Regulatory Compliance
- •FDA 21 CFR Part 211 (cGMP)
- •EU GMP Annex 1 (Sterile Products)
- •ISO 14644 (Cleanroom Standards)
- •PIC/S Guidelines
- •ICH Q9 (Quality Risk Management)
Key Performance Indicators (KPIs)
Media Fill Success Rate
100%
Target: Zero contamination
Environmental Excursions
<2%
Alert/Action limits
Deviation Rate
<1%
Per 1000 operations
CAPA Closure Time
<30d
Average timeline