Session 1 : Validation Principles and Cleaning Validation
• Evolution of cleaning and cleaning validation in the pharmaceutical industry
• What validation applies to
• Critical cleaning processes
• Cleaning objectives
• Validation vs. verification
• Overview of validation principles
Session 2 : Regulatory Background
• Cleaning validation guidelines (U.S. and European Union)
• Relevant cGMP notes
• 11 CFR 210/211
• Current 483s related to cleaning and cleaning validation
Session 3 : Validation Master Plans
• Content of master plan
• Rationale
• Value
Session 1 : Cleaning Process Parameters and Scale Up
• Temperature, agitation, concentration, time
• Pharma and biotech soils, soil levels, soil conditions
• Miscellaneous process parameters
• Laboratory and pilot studies
• Scaling-up parameters for manual vs. automated cleaning
Cleaning Agents
• Options and description
• Rationale for the selection of specific cleaning agent(s)
• Efficiency of residue removal and speed of wash-out
• Physical and chemical characteristics of agent
• Residue evaluation
Session 2: Equipment Design Considerations
• Typical pharma and biotech equipment cleaning
• Pipe sizing, flow through pipes, dead legs
• Seals, drainability, pitch, etc.
• Spray ball coverage, coverage testing
• Materials of construction
Writing Effective SOPs
• Recommended documentation structure and format
• Level of detail
• Upgrading manual SOPs
Session 3 : Selection of Most Suitable Analytical Method for Determination of Residue
• Choosing quantitative, specific and sensitive residue analysis
• Method validation requirements
• Visual inspection: advantages and disadvantages
• pH
• Conductivity-in-process screen
• Total Organic Carbon (TOC)
• Titrations
• UV-VIS spectrophotometry
• HPLC
Session 1 : Setting Cleaning Residue Limits
• Use of therapeutic or dose rationale for calculation of cleaning limit
• Use of toxicological approach for non-therapeutics or highly toxic agents (safety factor)
• Assay detection limit method
• Visual inspection, detection and examination
• Limits determination for rinsate, swab
Sampling Methods and Recovery Studies
• Type of technique: rinsate, surface sampling or swabbing, visual inspection
• Identification of proper rinsing solvent and swab composition
• Determination of proper swab technique
• Sample type, quantity, identification, location, size, container, method and materials
• Correction of analytical calculations based on accuracy/recovery results
Sesion 2 : Microbiological Control of Validated Cleaning and Sanitization Procedures
• Comparison of biopharmaceutical vs. pharmaceutical facilities
• Monitoring requirements for sterile vs. non-sterile facilities
• What and why
• Monitoring procedures
• Sample selection
• Media/incubation parameters
• Identification of isolates
• Establishment of alert and action levels
• Trending data
• Investigation and corrective actions
Session 3 : Cleaning Validation Protocols
• Process design/description and flowchart for each SOP for equipment
• Process capability
• Specifying residue challenge type and amount
• Acceptance criteria and limits calculations
• Appropriate cleaning SOPs and sampling procedures
• Proper documentation: IQ, OQ, PQ structure
• Monitoring and checklist of activities
• Execution and results interpretation
• Defining scopes and protocols
Cleaning Validation Strategies
18(hours)