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Pharmaceutical MicrobiologyMultidisciplinary Integrated Approach in Drug Manufacturing
Obaid Ali & Roohi B. ObaidCivil Service Officers, Government of Pakistan
5/5Inspections & Aseptic Processing Area
Managing an Aseptic Processing Area (APA)
Drug Product Sterilization Process Sterile Drug
Containers Sterilization Process
Sterile Container
Excipient Sterilization Process
Sterile Excipient
Closures Sterilization Process
Sterile Closures
Contact Surface
Sterilization Process
Sterile Contact Surface
Managing of all these steps is a real challenge for personnel
Working in an Aseptic Processing Area (APA)
Personnel
Knowledge
Ability
Skill
Atypical Job
Heavy gowning
Physical Exhaustion
Technical understanding
Very important
Educational background
K, A, S
Personal attributes
Grade A
Grade B
Grade C
Grade D
Process, Facilities
& Design
Personnel with
appropriate K,A,S
Training (Knowledge
based & performance)
Monitoring performance
Effective CAPAs
Aseptic Process
Connecting the Dots
Build Quality
Be proactive …. Rigorous thinking with logical, systematic &
science based approaches to improve effectiveness & efficiency of decision
making
Personnel & material flow
Air flow pattern evaluation
Aseptic operations
Disinfectant/ Sanitization
Cleaning efficiency
EM Plan
…… Inspector’s eyes looking for ……
Systems that allow inferior product to the market
Quality Management System
Production & Control Strategy
Potential adulteration boulevard
Consistency affairs
Contamination affairs
Identification & Traceability avenues
Reliability & reproducibility of results
Genuineness & accuracy of data
Validation Policy, Plan, Protocol, Report & Raw Data
Reports & Reviews
Developmental reports & Change Controls
Deviation, non-conformance, incidents
OOS, CAPA, OOT
Trainings & Effectiveness
Storage, Transportation
Human practice in aseptic areas
Sterility Failures
Media Fills
Rejects, Reworks, Re-process
Equipment repairing
Utilities & Plumbing Connections
Equipment logs
Maintenance Records
Cleaning Records
Observed Practice vs. Validated Practices
Personnel observed vs. Expected behavior
In-process store
SOP in place
Calibration stickers
Non-validated analytical methods
Growth promotion negative controls
Degree of product & process
understanding
Robustness of Quality System controlling the
process
Manufacturer’ ability to manage
risk associated with product
quality
Lets understand
GMP Inspection & Inspector’s Interest
Quality
Materials
Production
Laboratory Control
Facilities & Equipment
Packaging & Labeling
Quality
Review/approved procedure
Documentation of operation execution
Investigation Deviations
& Complaints
Failures
Production
Control Strategy
for change
Process validation
Investigation of
discrepancy
Missing & incomplete
records
In-process controls
Laboratory Control
Control Strategy
for change
Source of microbial
contamination
Investigation of
discrepancy Retention
of raw data
In-adequate sampling
Facilities & Equipment
Contamination
Cleaning procedure
Investigation of
discrepancy Equipment
qualification
Control strategy for
change
Materials
Identity test
Authenticity of COA
Investigation of
discrepancy
Control strategy for change in
handling of materials
Release of material
Packaging &
Labeling
Potential of mislabeling
Mix up potential
Investigation of discrepancy
Control strategy for
change
Packaging validation
Be Compliant and in state of Control
Aging infrastructure
Regular Assessment, Repair, Expertise, Risk Management
Conformance to Standards
compliant, competent in
microbial risk
assessment?
Culture
• Inherent human characteristic
Employee behaviors
• Absent or lagging change or behaviorDocumentation
• Expertise, Knowledge, CommunicationOversight
Key Compliance Root Cause Themes
• Human factorsEquipment design
• Appropriate, regularity, expertise & know-how
Equipment adjustment
• Risk Mitigation Activities absentEnvironment
Key Compliance Root Cause Themes
Lets sketch map
Lets count the dots to reconcile
Engineers design and
install
Validation department
executes validation
Production department performs
production
Maintenance department performs
maintenance
Quality Control performs tests
Quality Assurance
reviews and approves
Lets separate the dots to reconcile
Microorganisms unique to your
facility and operation
Personnel and material flow
Air flow pattern evaluations
Observation of aseptic filling operation
Environmental monitoring sample site selection
