Define Critical Cleaning

Chemistry of Cleaning Organic solvents Alcohols Ethers Petrochemical Only clean residues that are soluble in them Volatile Organic Carbon Concerns Flammability Concerns Waste Disposal Concerns Chemistry of Cleaning Water Only cleans things soluble in it Excellent where water alone will work Commodity chemicals (aqueous) Caustic soda and potash (NaOH & KOH) Phosphoric and nitric acid Single cleaning mechanisms of alkaline or acid attack Require high concentrations, no synergistic cleaning Waste disposal concerns Chemistry of Cleaning Detergent for Critical Cleaning Aqueous – blend Surfactant – anionic, nonionic, cationic Builders – chelation, anti-re-deposition, silicates Additives – enzymes, rinse aids Cleaning Methods (COP focused) Soak Scrubbing Agitated Immersion Ultrasonic Bubbled Pump under immersion Manual Cleaning COP Cleaning Processes Soak Low cost of capital equipment Easy to perform No Computer System Validation (CSV) Ultrasonic Cavitations release massive energy at the surface residual interface Usable on a wide variety of materials of construction Usually 40+ kHz Manual Cleaning Scrub Wipes – especially single use and should be non shedding Brushes (nylon may be degraded by alkaline cleaners) – smooth cleanable brushes of polypropylene can be more desirable Non abrasive pads (best to use robust pads that do not degrade and leave insoluble fibers) Abrasives (may be undesirable due to harming equipment and potentially leaving insoluble solid abrasive residues) Sponges – sometimes not desirable due to leaching compounds and harboring microbes Manual Cleaning Manual Cleaning mechanisms Dominant manual cleaning mechanisms Emulsification – Far better than low foaming used in CIP Supported by sequestering Dispersing Less participating cleaning mechanisms Lifting by Wetting Saponification – to the extent milder cleaners are used Acid and base hydrolysis – to the extent milder cleaners are used Manual Cleaning Advantages Able to use high emulsifying detergents Visual inspection by operators Mechanical energy from scrubbing Uniform & reproducible mechanical ultrasonic energy Lower boundary layers - sub-micron particles with higher frequencies Higher tend to be better for smaller particles Often uses milder, easier to dispose of chemicals Sometimes only option when equipment is small or for tools, and small fittings Manual Cleaning Disadvantages Requires labor Needs appropriate PPE Safety issues Soak cleaning volume vs. automated CIP cleaning May have variability Detergent Selection Hard to Choose Which Cleaner Over 3000 Cleaner suppliers Quality levels ranging from appearance grade to semiconductor quality There are formulations for gross soil removal and fine trace soil removal Formulations change for economy, performance or marketing claims Detergent Selection Regulatory Support One should choose brands that are cGMP compliant: Precise formulations & quality control Lot-specific COA, technical bulletins & SDS should be available Comprehensive cGMP compliance support Documentation available Lot traceability of cleaners Toxicity data Ingredient reactivity information Cleaner shelf-life testing Cleaning validation support Written cleaning procedures Cleaning Process Development and Optimization The 9 Variables of Effective Cleaning Success is more than Detergent The 9 variables: BATH-O-CARD 1. Before-clean 2. Agitation 3. Time 4. Heat 5. Orientation 6. Chemistry/Conc. 7. After-clean 8. Rinsing 9. Drying Cleaning Process Development and Optimization Process Conclusion – A Lifestyle Approach Selecting the right cleaner is easier if you understand the 9 variables that effect cleaning performance Match your cleaner to the cleaning method, substrate, and type of residue Then evaluate health and environmental safety The 9 variables intrinsic to cleaning process → cleaning validation → clean product Cleaning Validation/Verification Validating the use of a cleaner: Identify Cleaner Residues Select a Residue Detection Method Choose a Sampling Method Validate a Residue Detection Method Construct Recovery Studies Set Residue acceptance criteria Validate the cleaning process with the new cleaner Including design of experiments for optimal process Including three consecutive cleaning trials Including and Creating the Validation Report Write procedures and train operators Cleaning Validation/Verification Validating the use of a cleaner: Detergent Residue Detection - Specific vs. non-specific Specific ingredients: high performance liquid chromatography (HPLC) ion selective electrodes flame photometry UV spectroscopy enzymatic detection Titration Blend of ingredients: total organic carbon pH Conductivity Visual inspection Contact Angle (portabl) Cleaning Validation/Verification Summary Critical cleaning steps effecting the quality, safety or manufacture “Hot Spot” or worst-case locations Validation is achieved by proving that a process operates within predetermined parameters Manual Cleaning ---- consider both detergent and product residues ADE/PDE as detergent limits Limits for the active drug Excipients Degradation products Cleaning agents Bioburden Endotoxins COP Cleaning Case Study Pharmaceutical Company Case Study Progesterone/estrogen combination therapy highly water insoluble nature of progesterone/estrogen steroid structure Cleaning doesn’t scale “nicely” Inconsistency at large scale Move away from their typical CIP low foaming? COP Cleaning Case Study Pharmaceutical Company Case Study More than just a residual Very low level requirement Cytotoxic, antibiotic, and hormones COP Cleaning Case Study Pharmaceutical Company Case Study Consideration of more aggressive CIP detergent Consideration of a new CIP system Consideration of a higher foaming, COP process Ultrasonic/soak of parts Scrubbing of equipment that can’t be soaked/sonicated Flowing water rinse COP Cleaning Case Study Pharmaceutical Company Case Study Able to consistently meet cleaning requirements Validate using a “manual” higher foaming detergent Both specific and non specific used High emulsifying ability to more easily remove Progesterone/Estrogen COP Cleaning Case Study 2 OTC Skin Product Adherent, waterproof compound – mascara Customer looking to COP Instruments and small parts/vessels Experience indicates using Keylajet detergent and optimizing parameters COP Cleaning Case Study 2 OTC Skin Product KJ worked to some degree… It was noted the oily remained – add emulsification 85/15 % blend of roughly 3% KJ/LQ. Powerful concept of detergent blends When manual/COP involved with proper PPE, foaming or non foaming not the issue, best chemistry is COP Cleaning Case Study 3 Nutraceutical Turmeric, acidic components, collagen Needs oxidation, acid cleaner, protease? What we know – Collagen swells in presence of alkaline Acid cleans acid Turmeric aromatic compounds cleaned by oxidation COP Cleaning Case Study 3 Nutraceutical Determine if Citranox (acidic detergent) cleans alone Removes most collagen and acid residues Rust colored residue remaining – aka turmeric Follow with alkaline + oxidative detergent – Detojet Typical alkaline then acid reversed Follow the science - Verified on full scale