MAVF Session 3 Cleaning Lab Studies PDF

SESSION 3: CLEANING LABORATORY STUDIES STAGE 1 OF THE CLEANING VALIDATION LIFE CYCLE  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  Worst-case soiling material (Experiment...

SESSION 3: CLEANING LABORATORY STUDIES STAGE 1 OF THE CLEANING VALIDATION LIFE CYCLE  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  Worst-case soiling material (Experiment Product Characterization) LAB SCALE STUDIES AND SCIENTIFIC ANALYSIS Simple and recommended workflow to effectively use DoE (Design of Equipment): 1. Perform an Ishikawa analysis of parameters potentially affecting the cleaning process 2. Perform a definitive screening design of the hardest-to-clean product to identify critical factors from the Ishikawa analysis 3. Use DoE of the critical factors on the hardest-to-clean product to select parameter settings and optimize the cleaning process 4. Determine the cleanability of all products to identify the hardest-to-clean  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  Product Characterization Assessment SCIENTIFIC ANALYSIS – PRODUCT AND MATERIAL CHARACTERIZATION Product Characterization Assessment Component Name Chemical Composition Organic / Inorganic Molecular Weight Concentration LD50 Toxicity Carbon content based on actual concentration Viscosity  Product Characterization Assessment SCIENTIFIC ANALYSIS – PRODUCT AND MATERIAL CHARACTERIZATION Product Characterization Assessment Degradation Time Frame Solubility Solubility Index Cleanability Added to Process Stage Rationale and Purpose of Usage in the product Reference Material  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  TACT TACT CRITICAL PROCESS PARAMETERS FOR CLEANING Time Action Concentration / Chemistry Temperature  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  Active Cleaning Limits WORST-CASE DETERMINATION Crucial Step In Defining Contamination Limits Batch Solubility Contact Toxicity Release Cleanability mechanism size Potency Area  Activesoiling Worst-case Cleaning material (Experiment Product Limits Characterization) WHAT ARE BEING REMOVED Active Ingredient Decomposition product of active ingredient Microbial contamination Endotoxins Sanitizing agent Lubricant Environmental Dust Residual rinse water  Activesoiling Worst-case Cleaning material (Experiment Product Limits KEY ELEMENTS TO CONSIDER IN Characterization) DESIGN Equipment to be cleaned Soils to be removed Cleaning methods Cleaning agents Cleaning mechanism Cleaning parameters Residue limits  Activesoiling Worst-case Cleaning material (Experiment Product Limits Characterization) SOIL TYPES Actives, excipients, process materials, bioburden, endotoxin Amount of soils on surfaces Nature of soils on surfaces Freshly deposited Dried on during process Dried on during DHT Baked on during process Compacted  Activesoiling Worst-case Cleaning material (Experiment Product Limits Characterization) CLEANING EFFICIENY FACTORS Cleaning Solution Cleaning Agent Temperature Concentration Cleaning efficiency Solution Contact Time External Energy  Activesoiling Worst-case Cleaning material (Experiment Product Limits Characterization) METHODS Extent of automation Extent of disassembly Fixed CIP Portable CIP Parts washer Ultrasonic Manual (soak, brush, wipe, spray)  CONTENTS Worst-case soiling material (Experiment Product Characterization) Product Characterization Assessment Active Cleaning Limits Residue Limits TACT  Residue Limits QUESTIONS ON RESIDUE LIMITS What residues tested? How clean is clean? How low? Analytical methods used for measuring residues can perhaps affect selection of cleaning process, but is not typically a limiting factor  Residue Limits ANALYTICAL METHODS FOR CLEANING APPLICATIONS Residue specific assays Assay is unique to analyte Expensive, typically developed as part of the QC product analysis test suite Must be validated for use in cleaning application Residue non-specific assays Not unique to analyte Broad applications  Residue Limits ANALYTICAL METHODS FOR CLEANING APPLICATIONS Residue Specific Non-specific Assay Assay Advantages Highly specific Less expensive Highly sensitive Broad applications High precision Disadvantages Poor precision Low specificity Detection of only active molecules  Residue Limits RINSE WATER TESTING Relatively easy to perform Conducive to many analytical test methods Product specific (Bioassay, HPLC, LAL) Non-specific (pH, conductivity, TOC) Indirect measure of cleanliness  Residue Limits SURFACE TESTING Visual and Swabbing Direct measure of cleanliness More difficult to perform – typically required some breakdown of equipment to access hard to reach areas Swab sampling a defined surface area allows for quantification of assay results  Residue Limits SAMPLING AND TESTING METHODS Solvent Rinse Water Visual Surfac Swabbing e Contact plates - microbiological  Residue Limits VISUAL DETECTION Can detect many compounds down to levels of