Principles and Practice of Cleaning & Sterility in Place

CIP or in its full form, Cleaning in Place is defined as: Equipment and techniques to allow cleaning or process equipment without dismantling or manual cleaning with minimal operator involvement. What is CIP?

CIP / SIP - Definition CIP = Cleaning in Place – To clean the product contact surfaces of: vessels, equipment and pipework – in place – i.e. without dismantling SIP = Sterilize in Place – To ensure product contact surfaces are sufficiently sterile to minimise product infection.

CIP / SIP Involves the use of: – Chemicals – Sterilizers – High pressure pumps – Spray nozzles – Spray balls – Aseptic designs

CIP or SIP Ensures that the large scale processes are: – Free of dirt – Free of organic contaminants – Free of microorganisms

Benefits of CIP

Benefits, contd. It is: – Automatic – Reproducible – Reliable Delivery of: – Cleaning solutions – Rinsing – Washing To & through: – process equipment/piping Improves: – Product quality – Plant hygiene

How CIP Works? Mechanical – Removes ‘ loose ’ particles by Impact / Turbulence Chemical – Breaks up /removes remaining particles, if possible, by Chemical action Sterilant / Sanitizer –‘ Kills ’ remaining micro-organisms to an acceptable level

CIP Energy Solutions

Factors affecting CIP Mechanical Chemical Temperature Time

CIP Operation PRE-RINSE - Mechanical Removal DETERGENT - Cleaning of Remaining - Caustic, Acid or Both FINAL RINSE - Wash Residual Detergent STERILANT/SANITIZER - Cold or Hot

Vessel CIP Mains CIP Pre-Rinse 10 to 20 mins 5 to 10 mins Caustic Detergent 30 to 45 mins20 to 30 mins Rinse 10 to 15 mins5 to 10 mins Acid Detergent 20 to 30 mins15 to 20 mins Rinse 15 to 20 mins10 to 15 mins Sterilant 10 to 15 mins5 to 10 mins Typical CIP Times

Typical CIP Temperature Initial (Rx) VesselsHot 85°C Initial (Rx) MainsHot 85°C Process VesselsCold < 40°C Process MainsHot 75°C (Yeast) VesselsHot 75°C (Yeast) MainsHot 75°C

Water Used for Cleaning Process Quality of Water used for aqueous cleansing is critical for performance: Chemical properties (pH, hardness, etc.) Biological properties (bioburden, endotoxins) Pre-Rinsing. Solely for flushing out of residue prior to washing step. Usually based on practicality of what water is available. Washing. Most critical water hardness – effects efficiency of cleansing of aqueous surfactant solutions. Rinsing. In general, the final rinse used for equipment should use the same quality of water as used in the final stage of manufacture.

CIP Detergent - Requirements Effective on target Non foaming or include anti-foam Free rinsing Non corrosive – Vessels/pipes, joints Controllable - Conductivity Environmental

Caustic Detergents Advantages – Excellent detergency properties when “ formulated ” – Disinfection properties, especially when used hot. – Effective at removal of protein – Auto strength control by conductivity meter – More effective than acid – Cost effective Disadvantages – Degraded by CO 2 forming carbonate. – Ineffective at removing inorganic scale. – Poor ability to rinse. – Not compatible with Aluminium – Activity affected by water hardness.

Acid Detergents Advantages – Effective at removal of inorganic scale – Not degraded by CO2 – Not affected by water hardness – Lends itself to automatic control by conductivity meter. – Readily rinsed Disadvantages – Less effective at removing organic soil. – Limited bio-cidal properties – High corrosion risk, Nitric Acid – Environment – Phosphate/Nitrate discharge

Detergent Additives Sequestrates (Chelating Agents) – Materials which can complex metal ions in solution, preventing precipitation of the insoluble salts of the metal ions – e.g. EDTA (Ethylene Diamine Tetra Acetic acid) Surfactants (Wetting Agents) – Reduce surface tension allowing detergent to reach metal surface.

Sterilant / Sanitizer Requirements Effective against target organisms Fast Acting Low Hazard Low Corrosion Non Tainting (An unpleasant odour and flavor) Acceptable Foam Characteristics

Sterilants / Sanitizers Chlorine Dioxide Hypochlorite Iodophor Acid Anionic Quaternary Ammonium Hydrogen Peroxide PAA (Per-oxy Acetic Acid)

CIP Systems Single Use – Water/Effluent/Energy costs Recovery – Detergent Recovery – Rinse/Interface Recovery Tank Allocation

Single Use vs Recovery Single Use CIP – Low Capital Cost – Small Space Req. – Low Contamination Risk – Total Loss High Water Use High Energy Use High Effluent Vols. – Longer Time/Delay – Use for Yeast Recovery CIP – High Capital Cost – Large Space Req. – Higher Contamination Risk – Low Loss Low Water Use Low Energy Use Low Effluent Vols. – Shorter Time/Delay – Use for Brewhouse & Fermenting

Types of CIP VESSEL CIP - Spray-head Selection - Scavenge Control MAINS CIP - Adequate Velocity - Total Route Coverage

Vessel CIP - Sprayheads Static Sprayballs – High Flow / Low Pressure Rotating Sprayheads – Low Flow / Medium Pressure Cleaning Machines – Low Flow / High Pressure – High Impact

Vessel CIP – Sprayballs Advantages – No moving parts – Low Capital Cost – Low pressure CIP supply – Verification by Flow Disadvantages – High Water & Energy Use – High Effluent volumes – Spray Atomises if Pressure High

Vessel CIP – Cleaning Machines Advantages – High impact, aggressive cleaning – Good for heavy duty cleaning – Low water/energy use – Low effluent – Effective in large vessels

Mains CIP Flow of CIP fluid from CIP supply, through process pipework and back to CIP set The entire process route must see: – turbulent CIP Flow

Thin Boundary Layer at pipe wall Turbulent Flow – Flat velocity profile – Thin Boundary layer – Effective CIP Laminar Flow – Streamline flow – Velocity profile, faster at centre – Ineffective CIP Mains CIP Turbulent & Laminar Flow

Typical CIP Program Step Operation Cleaning Agent Temp (°C) Time (Min.) Usage 1 Pre-RinseWater To drain 2 Alkali Clean2% Caustic Re-circulated 3 Inter-rinseWater To drain 4 Acid Clean1% Phosphoric Re-circulated 5 Inter-rinseWater To drain 6 Final RinseQuality Water To drain 7 Air PurgeSterile Air To drain

Why Use CIP? 1. CIP is superior to any cleaning method Automated, with parameter monitoring & control Repeatablility -> reliability Human errors eliminated Eliminate contaminated products

Why Use CIP? (pt. 2) 2) Lower operating costs Reduced labor costs Cleaning turnaround time reduced Water / solvents / detergents usage significantly reduced

Why Use CIP? (pt. 3) 3) Safety Improvement Reduced explosive of product to personnel No equipment dismantling / vessel entry Eliminates hazardous activities, eg HP water HP water blasting

What is the Result of CIP? CIP results in the equipment being chemically cleaned. This is defined as “the removal of all residues of soil and all CIP agents so that contact with the cleaned surface does not result in physical contamination.” If the equipment being cleaned needs to be microbiologically clean then an additional process can be carried out. This process is called SIP.

What is SIP? SIP or in its full form, Sterlilizing in place is the generic term for sanitizing, disinfecting or sterilizing equipment normally after a CIP clean. SIP results in the removal of any remaining microbiological contamination.

Typical Chemical Sanitizers are: Chlorine, hypochlorite, hydrogen peroxide, ozone, peracetic acid Sanitation or Disinfection is normally applied after the full CIP has been carried out. It is achieved by the introduction of a sanitizer or disinfectant chemical into the final rinse waters of the CIP Chemical SIP

Thermal sterilization has the advantage of affecting areas such as sample points, which may not be treated by chemical means. Thermal sterilization is achieved by the application of steam or hot water at a suitable temperature for a suitable firm Typical Thermal SIP methods are: dry heart, steam, superheated water. Thermal SIP