Cleaning Validation, Monitoring and Verification

DOC 45 CLEANING

September 2021

European

Hygienic Engineering and Design Group

EHEDG Headquarters

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CLEANING VALIDATION, VERIFICATION AND MONITORING*

September 2021 ©EHEDG

Dan Anderson

Lammert Baas

Karin Blacow***

Ellen Brinkman

David Childs

Olivier Couraud

Isabelle Guillard

Dr. John Holah

Holger Hölzemann

Gabe Miller

Dirk Nikoleiski***

Hein Timmerman

Thomas Tyborski

Dr. Patrick Wouters

Coca Cola, USA

LB F&B Support Services, The Netherlands

Commercial Food Sanitation, The Netherlands

FrieslandCampina, The Netherlands

Holchem Laboratories, UK

GSF SAS, France

Tetra Pak Packaging Solutions AB, Sweden

Kersia, UK

OSI International Holding GmbH, Germany

Process Innovation Food Safety, LLC, USA

Commercial Food Sanitation, Germany

Diversey, Belgium

Ecolab Europe GmbH, Germany

Cargill, The Netherlands

Hui Zhang** Unilever, The Netherlands

* Report prepared by the Working Group “Cleaning Validation” of the European Hygienic Engineering & Design Group (EHEDG)

** Chairman

*** Co-Chair

Summary

This guideline provides recommendations for establishing site specific cleaning validation, monitoring, and verification programs in a food manufacturing environment It explains the overall concept and provides templates and practical examples that can be used in order to establish validation, monitoring and verification programmes.

Introduction

The food industry must make products that meet quality standards and which can safely be consumed, whilst at the same time providing efficient processing lines and ensuring a safe working environment for operatives. Therefore, process, ancillary equipment and the environment need regular and effective cleaning, with or without disinfection, to ensure the control of such food safety, efficiency and operative safety functions and to prevent the cross-contamination of food products. Building constructors and equipment manufacturers also play a role in ensuring the management of these functions by providing building structures and equipment that are inherently cleanable. In the following text, cleaning or cleaning and disinfection will be referred to as "cleaning"

Cleaning validation is also becoming more important in the general philosophy of food safety with the recognition that HACCP prerequisites, such as cleaning, can be as important in managing food safety as food processing CCPs. To facilitate this, physical, chemical and biological cleanliness is a prerequisite for food safety as well as meeting quality standards and for brand protection reasons. A variety of hazards can contaminate food such as microorganisms and their toxins; food residues, particularly if allergens are present; residues of cleaning and disinfection agents and lubricants, and foreign bodies.

The validation of cleaning operations is necessary to provide documented evidence that an appropriate cleaning procedure will provide clean equipment, suitable for its intended use, and thus that cleaning procedures are compliant with best practice and third-party food safety standards. Following a validated cleaning baseline, optimization of the cleaning operation can subsequently be undertaken, with a subsequent reduction of chemicals, energy, water, labour, downtime and effluents, whilst maintaining the validated objectives of the clean

Appropriate monitoring and verification programs should be implemented to ensure validated cleaning protocols are being adhered to and are operating as intended on an ongoing basis.

Objectives and scope

This document is intended as a guideline for food manufacturers on how to perform the validation, monitoring and verification of the cleaning and disinfection programmes of the entire manufacturing asset. This guideline provides the overall concept, templates including practical examples, that can be used in order to establish validation, monitoring and verification programmes (See Annex)

More detailed information about cleaning and disinfection can be found in the EHEDG Doc 52 “Basic Principles of Cleaning & Disinfection in Food Manufacturing”. Details about CIP will be found in the EHEDG Doc 50 “Hygienic design requirements of CIP installations” and tank cleaning EHEDG Doc 51 “Tank Cleaning” (will be published soon).

This guideline provides general advice and does not cover specific validation, monitoring and verification programs.

Normative References

The following documents contain provisions that, through reference, constitute provisions of this EHEDG Guideline. At the time this guideline was prepared, the editions listed below were valid. All documents are subject to revision and parties are encouraged to investigate the possibility of applying the most recent editions of the documents indicated below.

‒ Codex Alimentarius, Food Hygiene (Basic Texts)

‒ ISO 18593:2018(en) Microbiology of the food chain Horizontal methods for surface sampling

‒ ISO 22000 Food safety management systems - Requirements for any organization in the food chain (2018).

Definition of Terms

The definitions of the EHEDG Glossary (V4-2020) apply to this document. Definitions specific to this document are given below.

Change Management

A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action to ensure and document that the system is maintained in a validated state.

Cleaning validation

Obtaining the documented evidence that cleaning with or without disinfection processes, if properly implemented, is effective at achieving a predefined level of hygiene on product contact surfaces identified during the hazard evaluation.

Concurrent cleaning validation

Obtaining the documented evidence that current cleaning processes, under worst case conditions, have been effective and will work in the future.

Design Qualification

An iterative verification process during the design stage of a hygienic entity to confirm a proposed design will meet the requirements it needs to fulfil.

Equipment Qualification

The formal process of obtaining the documented evidence that the equipment is fit for its intended use or that appropriate mitigation steps have been implemented. (For example, if an area of equipment cannot be easily cleaned, and cannot be redesigned, mitigation would be the need for dismantling prior to cleaning). Qualification is a part of (the initial stage of) validation, but the individual qualification steps alone do not constitute process validation.

Monitoring

(Codex Alimentarius) The act of conducting a planned sequence of observations or measurements of control parameters to assess whether a control measure is under control

(ISO 22000) Conducting a planned sequence of observations or measurements to assess whether control measures are operating as intended

(NACMCF, USA) A planned sequence of observations or measurements to assess whether a CCP is under control and to produce an accurate record for future use in verification

Product contact surfaces

Surfaces exposed intentionally or unintentionally to the product and surfaces from which splashed product, condensate, liquids or material may drain, drop, diffuse or be drawn into the product or onto product contact surfaces or surfaces that come into contact with product contact surfaces of packaging materials.

Prospective cleaning validation

Obtaining the documented evidence that future cleaning processes, while applying known worst case conditions, will be effective.

Retrospective validation

Obtaining the documented evidence that existing cleaning processes, based on historical data, have been effective in the past and, on the condition that product composition, process, production equipment and cleaning programmes remain unchanged, will also work in the future.

Revalidation

Repeated validation of an approved process (or a part thereof) to ensure continued compliance with established requirements.

Standard operating procedure (SOP)

An authorized written document giving instructions for performing operations (e.g., equipment operation, maintenance and cleaning, sampling, analyses).

Validation, General

(EHEDG Doc. 34) Documented evidence that a hygienic entity (process, procedure or analytical methods) can deliver conformity with the user (stakeholders) specification.

(Codex Alimentarius) Obtaining evidence that a control measure or combination of control measures, if properly implemented, is capable of controlling a hazard to a specified outcome Validation involves measuring performance against a desired food safety outcome or target, in respect of a required level of hazard control. Validation is performed at the time a control measure or a food safety control system is designed, or when changes indicate the need for re-validation. Validation of control measures is, whenever possible, performed before their full implementation.

(ISO 22000) Obtaining evidence that the control measures managed by the HACCP plan and by the operational prerequisite programs (oPRPs) are capable of being effective

Validation protocol (or plan)

An approved document describing the activities to be performed in a validation, including the acceptance criteria for the approval of a cleaning process and the validation personnel’s responsibilities.

Validation report

An approved document in which the records, results and evaluation of a completed validation programme are assembled and summarized. It may also contain proposals for the improvement of processing and/or equipment.

Verification

(Codex Alimentarius) The application of methods, procedures, tests and other evaluations, in addition to monitoring, to determine whether a control measure is or has been operating as intended.

(ISO22000) Confirmation, through the provision of objective evidence, that specified requirements have been fulfilled

Worst-case

A condition or set of conditions encompassing the upper or lower processing limits for operating parameters and circumstances, within SOPs, which pose the greatest chance of product or process failure when compared to ideal conditions.

General Considerations

There are many reasons for cleaning, some of which are listed in Table 4.1. These range from keeping the workplace tidy (housekeeping) to specific programmes to free processing equipment from hazards such as allergens and pathogens.

All cleaning programmes require validation, monitoring and verification (see 4.1), though the degree of validation, monitoring and verification will vary with the objectives of the clean. Generic cleans, e.g. as developed for new buildings and equipment (see 4.2), may require basic validation to establish that they are fit for purpose and may require infrequent monitoring and verification. Other cleaning programmes, particularly those that control hazards (see 4.3), will require enhanced validation with detailed document and frequent, subsequent, monitoring and verification. Such validation studies are likely to be audited by regulatory authorities, customers, and other audit bodies

The degree of validation is also associated with the accessibility of equipment surfaces. If the objective of the cleaning is visual cleanliness, enhanced cleaning validation is not usually required for open surfaces. This is because the monitoring for visual cleanliness by inspection or rapid hygiene methods, should occur after every cleaning, so in effect, cleaning is being ‘validated’ every time it is undertaken. For closed surfaces (e.g CIP) where the cleaned surfaces cannot be readily inspected, enhanced cleaning validation maybe required. Guidance on the degree of validation and the frequency of monitoring and verification, dependent on the objectives of the clean, is given in Table 4.1.

Cleaning validation should be undertaken for new installations (see 4.2) and if major changes occur (see 5.4). Existing (legacy) installations (see 4.4), which have been traditionally controlled by monitoring and verification, may require a concurrent or retrospective validation (see 4.1).

If the validation process to be undertaken is likely to require sampling/inspection of the line that is not routine, e.g if it is necessary to:

• undertake extra dismantling

• access a guarded area

• access difficult to reach areas

• physically enter into equipment

• work at heights

• etc.

appropriate health and safety risk assessments should be completed.

It is the responsibility of the food manufacturer to validate the cleaning and disinfection procedure. Cleaning validation is best performed with input and/or participation from stakeholders including the equipment supplier, cleaning chemicals supplier, any cleaning contractors and specific customers, as appropriate.

Reason for cleaning

Provide a safe working environment for operatives (housekeeping)

Undertake a clean-as-you-go for GHP/GMP

Extend the life of, and prevent damage to equipment and services

Maintain plant operating parameters during food processing including heat transfer and flow parameters

Remove materials that could lead to foreign body contamination or could provide food or shelter for pests

Remove food soils that would be detrimental to the organoleptic quality of subsequent production runs

Remove DNA to prevent e.g. one meat species (e.g. pork) contamination of subsequent production runs (e.g. beef) in a factory processing multiple animal species

Remove spoilage microorganisms to maintain or potentially extend product shelf-life

Remove cleaning chemical residues, particularly if they are associated with a regulated maximum residue limit (MRL)

Remove allergens to prevent contamination of subsequent production runs

Remove pathogens that may contaminate food products

Visual cleanliness Basic Infrequent

Visual cleanliness Basic Infrequent

Visual cleanliness Basic Infrequent

Visual cleanliness Basic Frequent

Visual cleanliness Basic Frequent

Visual cleanliness Basic Frequent

Visual cleanliness

Absence* of DNA Enhanced Optional Every clean

Visual cleanliness

Absence* of Spoilage microorganisms

Visual cleanliness

Absence* of chemical residues

Visual cleanliness

Absence* of allergens

Visual cleanliness

Absence* of pathogens

Enhanced Optional Every clean

Enhanced Every clean

Enhanced Every clean

Enhanced Every clean

Table 4.1 – The objectives of a range of cleaning programmes, together with their suggested degree of validation and frequency of monitoring and verification (*: Absence based on pre-determined level)

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Validation, monitoring and verification

Cleaning validation, monitoring and verification are related concepts to demonstrate that a cleaning regime shows effective and consistent results (see Fig 4.1). The outcome of cleaning validation will typically give directions and provide acceptance criteria for setting up the verification and monitoring programmes, which follow cleaning validation and which confirm that the cleaning protocols are being adhered to and are operating as intended.

Validation Personal copy of: Pieter de Haan, pdehaan@stonhard.com, 24.03.2023 19:28:50, IP: 189.244.53.247

Verification

Validation - Does it work?

Demonstrates that a cleaning procedure (Standard Operating Procedure, SOP) is effective in achieving the predetermined required level of cleanliness, whilst applying expected worst-case conditions. Once a cleaning procedure has been validated, then it is routinely applied and the process should be monitored and verified. Revalidation may be required following changes to the equipment, manufacturing process or cleaning procedure.

Monitoring – Is it working?

Monitoring cleaning effectiveness is performed during every cleaning procedure. It includes a planned sequence of observations, measurements, records and documentation of control parameters, to assess whether the cleaning procedure is performing within specifications. Monitoring activities are typically “real-time” measurements during cleaning.

Verification – Has it worked?

Verification determines that the control parameters have been implemented as intended. Verification occurs during or after the cleaning procedure through a variety of activities, including observation of monitoring activities and review of records

Cleaning validation can be performed in three different ways: prospective, concurrent and retrospective cleaning validation. The principles of prospective and concurrent validation are the same, and are described in this guideline document.

Prospective cleaning validation is completed before finished product that is intended for sale will be produced on newly installed or modified food manufacturing equipment. Evidence that the cleaning procedure is capable of meeting its objectives will be obtained The validation report should be reviewed and approved, before the equipment is released for routine production.

Figure 4.1: The interrelationship of validation, monitoring and verification

Concurrent cleaning validation is applied, if it is impractical to complete a cleaning validation before finished product that is intended for sale will be produced for a new or modified process, or if validation is being undertaken on an existing process that has not historically been validated. As with prospective cleaning validation, testing will be undertaken

Concurrent cleaning validation is the recommended approach for re-validation at scheduled intervals (See 5.4)

Retrospective cleaning validation is based on the analysis of historical data to provide documentary evidence that the cleaning protocol is effective. It refers to a cleaning programme that has been implemented for some time.

Retrospective cleaning validation, particularly if the cleaning programme has been running for a long time without changes in the product or process, has the advantage that it is likely that during this time, all worst-case scenarios in terms of product soils and cleaning parameters will have been tested in practice. However, monitoring and verification may not have been undertaken at the hardest to clean areas of the process equipment.

If it can be demonstrated that verification and monitoring has included the hardest parts of the equipment to clean, and that the process has been running unchanged for a long time (usually seen as >1 year so all seasonal trends have been observed), then retrospective validation can be comprehensive and acceptable. For all other occasions, where worst case scenarios have not been fully accounted for, concurrent cleaning validation should be undertaken.

“V”-model for new equipment installations and facilities

A well-established structure for project-management is represented by the “V”-model (See Figure 4.2). It gives an overview of typical project phases, when hygienic entities should be specified and qualified, and when these entities should be validated during the corresponding built/fabrication phases.

Cleaning requirements should be defined by the user (food manufacturer), as well as how the effectiveness of the cleaning procedure(s) will be validated. These details should be documented in the User Requirement Specification (URS). Equipment manufactures should provide cleaning recommendations that can be used as input for a URS.

The functional specification(s) and to a greater level of detail the design specification(s) will translate the URS into design solutions. As part of the design qualification process, the anticipated cleaning procedure(s) and the corresponding design solutions should be reviewed at the various successive stages during the design stage before an entity is built/fabricated.

For equipment the URS and the functional specification should include:

• objective of the cleaning

• cleaning times and frequencies

• methods of cleaning

• target level of cleanliness

• cleaning validation protocol (Cleaning Validation Master Plan, see section 5 of this document)

• anticipated monitoring and verification requirements (e.g sensors, probes,etc.)

These details should become a contractual element between the user (food manufacturer) and suppliers (equipment manufacturers) as part of the performance guarantee, which needs to be confirmed.

The process of qualification should follow the directions given in EHEDG Doc. No. 34, Integration of Hygienic and Aseptic Systems. The CIP installation qualification should follow the directions given in EHEDG Doc. No. 50, Hygienic Design Requirements for CIP Installations.

The completion of cleaning validation activities typically fall into the process validation step, but may be initiated and started at earlier stages after hygienic entities are built/fabricated. Initial cleaning validation activities may be done after short production runs during the commercialisation phase and run lengths may be extended over time up to the anticipated maximum run length.

Cleaning Validation and HACCP

As a Hazard Analysis Critical Control Point (HACCP) prerequisite (Codex, 2007), cleaning and disinfection has always been regarded as important and, as a key good manufacturing practice (GMP), it’s effectiveness has traditionally been actively assessed and reviewed. More recently, audit programs based on the Global Food Safety Initiative (GFSI) benchmarking standards have recognised the concept of validation. GFSI recognised standards, such as the British Retail Consortium (BRC) Global Standard for Food Safety, the International Featured Standards (IFS) Food, the Safe Quality Food (SQF) code, and the Food Safety Certification Scheme (FSCC) 22000 have raised the importance and profile of cleaning validation within food manufacturing and guidance on how it can be effectively and universally implemented is required.

Detailed and documented cleaning validation is essential if the objective of a cleaning program is to control hazards (e.g. pathogens, allergens, chemical residues), and these cleaning programmes may be raised to the status of operational pre-requisites.

This level of cleaning validation may be required for brand protection (e.g. DNA, spoilage microorganisms), quality and process performance (efficiency). These are not hazards, but the food manufacturer may think that they are of high importance for such brand protection and thus may chose an enhanced validation.

Legacy Equipment Installations

For older installations hygienic design reviews might not have been done to qualify equipment or documentation is not available. In this case it is recommended to include a formal and documented hygienic design risk assessment in the validation protocol to capture hygienic design flaws and to determine corrective actions required. This may result in either design changes or periodic deep cleaning activities to manage potential risks. The hygienic design risk assessment might be done during the tear down inspection, as the installation will be easy to access then.

Figure 4.2: “V”-model: Project stages with various qualification and validation steps.

Cleaning Validation Master Plan

A cleaning validation master plan is a structured approach to identify and explain the steps to complete the validation. Following all the steps in this plan will be sufficient to ensure enhanced validation (Table 4.1). Following some of these steps will be sufficient to demonstrate basic validation of a cleaning programme, with the number and detail of these steps being selected by the food manufacturer.

The master plan contains the validation protocol, the execution of the cleaning validation, the cleaning validation report and revalidation (see 5.1)

The validation protocol

A cleaning validation protocol should be established to define the procedure on how the cleaning process will be validated. The protocol should include:

• Objective

• Responsibilities

• Scope (Description of the process or part of the process that shall be validated)

• Number of repeats

• Validation Input Requirement: list of the following documents with identification numbers and issue dates, which includes for example

‒ Qualification evidence including Process and Instrumentation Diagrams (P&IDs) of the equipment to be cleaned (see Doc. 34)

‒ Qualification evidence CIP installation including P&ID's (see Doc. 50)

‒ Standard Operating Procedures (SOP) for the cleaning (and disinfection, if applicable),

‒ Calibration records

‒ Maintenance records

‒ Analytical data of water quality (e.g. hardness, micro data, pH etc..)

‒ Specifications of the cleaning equipment other than CIP

‒ Specifications of chemicals used including the general efficacy against the targeted contaminants

‒ Cleaning training records of staff

• For revalidations: historical data of monitoring and verification activities (out-of-limits situations and the completion of corrective actions).

• Selection of worst case conditions

• Identification of relevant contaminants

• Sampling and testing (number of samples, locations/areas to be sampled, analytical methods)

• Acceptance criteria

Number of repeats

The minimum number of successful runs (prospective and concurrent) should be risk assessed in order to demonstrate a high level of assurance that the cleaning regime is effective and consistent. For deciding a reasonable number the following criteria should be considered:

• Hazard to be managed

• Intended use of final products (e.g. infant formula)

• Similarity of validated cleaning procedures

• Similarity of production processes

Figure 5.1: The elements of the cleaning validation master plan

Validation protocol (5.1)

Execution of the cleaning validation (5.2)

Cleaning validation report (5.3)

Revalidation (5.4)

• Similarity of soil characteristics

• Historical data of the similarities above in terms of validation, monitoring, and verification activities

• Results from initial cleaning trials after commissioning (data typically gained after short production runs/trials)

• Frequency of production runs

Three successful executions of the cleaning procedure should be sufficient to prove that the cleaning is validated.

For due diligence, the cleaning procedure for newly installed equipment should be validated on three consecutive occasions (before finished product for sale is being produced). Please note that if only prospective validation studies are undertaken, the worst case may not be reflected. It is recommended to combine prospective and concurrent validation.

Selection of worst-case conditions

When possible (for prospective validation), it is recommended to use actual product under the normal conditions of production. It is recommended that the worst-case situation is chosen as regards soil characteristics to represent the most difficult to clean product manufactured and the most difficult areas (features, geometries, dead areas) of the equipment to be cleaned. For similar products and processes, representative products and processes considering worst-case situations should be selected. The results of the worst-case validations can be transferred to products that, for example, form residues that are easier to remove and/or have less risk potential. In this way, product groups that are manufactured in a validated system can be grouped together. It is also common practice to combine groups of identical equipment and to transfer the validation of one of these systems to the whole assembly. In this way the validation effort can be reduced

The cleaning to be validated should be reviewed to identify worst case conditions regarding cleaning conditions and soiling of the equipment. Worst case conditions should be selected to ensure that the validation study is valid for all conditions in practice. This means that the most difficult product/process combination should be selected, the longest run times etc. It is important that the validation study is executed under normal conditions, which means that the level of supervision during cleaning is the same as normal and that the same operators as normal execute the process. The conditions chosen should be within acceptable process limits.

Worst case conditions may include:

• Cleaning conditions: e.g. least optimal temperature, cleaning agent concentration or flow

• Maximum time allowed between the end of manufacturing and the start of the cleaning process.

• Maximum time allowed between the completion of cleaning and the initiation of the subsequent manufacturing operation

• Product: most difficult to clean, representation of product family, high risk product (vulnerability of intended consumer). Product families may be assigned based on product characteristics (e.g. viscosity, particles, starch), microbiological risks, allergens, cleaning recipes and equipment

• Products with the highest levels of contaminants (allergens, microbial)

• Product with longest production run length

• Production conditions: e.g. process temperature, holding time

• Production schedule with the highest number of consecutive product formulations containing the contaminant of concern (soil age and build up)

Temporary sampling valves installed for process validation may become sources of contamination if poorly designed and integrated, and should be included in a worst case scenario

Identification of relevant contaminants

The contaminant to be controlled will determine the selection of the appropriate sampling and testing strategy. Relevant contaminants should be highlighted in the Validation Protocol and may include (one or more):

• Microbial contaminants

• Cleaning chemicals

• Allergens

• Foreign bodies

• GMO

• DNA

• Product residues (flavour, colour, ingredients, particles, or other quality related attributes, e.g. inorganic for organic product, animal origin for vegan product, pork for halal etc..)

Sampling and testing

The methods of sampling and testing should be established specifically for each cleaning validation and documented in a SOP. Sampling should be documented including the name of the sampler, sampling method and equipment, exact sampling location, date, deviations, visual assessment, etc.

A sampling plan and the required amount of samples should be established on a risk based approach to maximise probability of detecting contamination. The plan should consider the nature of the contaminant and the production equipment (design, size, number of difficult to clean areas, etc.).

Sampling can be required immediately after the execution of the cleaning process if recontamination from other sources than the equipment tested can occur, especially for open equipment.

Selection of sampling locations

The selection of sampling locations should consider critical spots or areas that are likely areas of increased risk. Examples are difficult to clean areas such as dead ends, the underside of tank lids, underneath mixing devices, large diameter pipes, couplings or gaskets. In particular, account should be taken of the areas where inadequate cleaning would lead to a high risk for product safety or quality. A selection should be made for example on the basis of Process and Instrumentation Diagrams (P&IDs), historical data, flow calculations (CIP) and hygienic design reviews. Based on the analysis, dismantling of the equipment may be required.

Methods of sampling

Two methods of sampling are usually applied, direct and indirect sampling. Often a combination of the two methods is required

Direct sampling of surfaces is the most commonly used method and includes swabs, wipes, sponges or scraping devices, test strips to sample predefined areas (typically 10x10 cm). ISO 18593 describes the sampling techniques with swabs and contact plates.

It should be considered that sampling, no matter which technique/device is used, collects only a fraction of the targeted contaminant (microbiological population or allergenic protein) of the sampled surface. The samples from equipment surfaces are not necessarily representative of a larger surface area. Various samples should be taken from places which are difficult to clean (worst case locations). The ratio of detected contaminant to the actual total contaminant which might not be detected, depends on many factors, such as the surface material, the microbiological population, the composition of the soil, the sampling device, the force of application, the individual doing the sampling, etc. As stated above, while a high level of contaminant is an indication of poor cleaning, its absence is not necessarily an indication of good cleaning. The detection of residual contaminant should lead to questioning the quality of the cleaning

Indirect sampling consists of sampling of rinse media (e.g. rinse water, oil, salt, sugar etc.) and products

Indirect: Rinse media

Rinse media sampling is normally applied to validate the cleaning of large areas, non-accessible systems (e.g. long pipe work) or systems that cannot be routinely disassembled (e.g. plate heat exchangers, homogenizers)

The analysis of rinse samples gives an indirect result of the line cleanliness, as the presence of contaminants in the rinse solution indicates when the removal of contaminant from the surface has stopped and not whether the surface is clean. If there are contaminants trapped within the equipment surface, the rinse medium sample will not be able to detect them. In order to have truly representative and consistent results, the contaminant to be analysed must be completely detached from the surface during cleaning and rinsing, and uniformly dispersed in the rinse medium.

Indirect: Product

During the next production run, especially at the beginning, the product flowing through the pipework and process equipment acts as a rinse fluid removing any residual product or cleaning fluids from the process line. Therefore, sampling of the first finished product of the next production run can be collected and analysed, similar to that conducted as part of routine product release protocols. The analyses can be focused to determine the microbiological quality of the final product, allergen content as well as some relevant product characteristics (e.g. pH, water content, and colour). Product sampling may be required at the start, middle and end of production, depending on risk assessment. As an example, contaminants may leak into the product in a different way (e.g. residue from a deadleg) in closed circuits as against open surfaces (e.g. residue left on a conveyor belt). For allergen cleaning validation, product sampling is essential.

Product should be sampled at different process steps to ensure that the entire process line is assessed. The various sampling sources are summarized in Table 5.1.

Direct Surface

• Insoluble

• Not removed from the surface during cleaning

• Trapped in difficult to clean areas of the equipment (e.g. dead ends)

Indirect Rinse media

• Removed from the surface during cleaning (final rinse)

• Uniformly dispersed in rinse media

• Soluble (if rinse media is water)

• Accessible product contact areas (e.g. tanks, open plant)

• Product contact areas of equipment that can be easily disassembled (e.g. pumps, pipework)

• Non-product contact surfaces

• Inaccessible systems (e.g. welded CIP pipework)

• Equipment that cannot be routinely disassembled (e.g. homogenizers, heat exchangers)

• Open equipment

• Small, defined sampling area

• Cannot sample every part of the machine, worst case areas of equipment must be identified (e.g. dead legs, rough welds, etc.)

• Indicative only; will not give information about the entire surface area.

• Large sampling area

• Does not indicate where difficult to clean areas are

• May indicate when removal of product from the surface has stopped, but not whether the surface is clean

• Large dilution effects.

• Can be used to follow the progression of cleaning (cleaning monitoring)

• Often the method of choice for dry cleaned process

Product • Removed from surface after cleaning with the next batch

• Allergen cleaning validation

• Should not be used in isolation without other sampling sources

• Out of limit results may indicate other contamination sources than poor cleaning

• Monitoring of cleaning efficacy

Methods to confirm cleaning effectiveness

Visual inspection and sensory evaluation

The primary pass criteria for cleaned objects should be visual cleanliness (no visible residue) and the absence of odours and films. It is not recommended to conduct any analytical sampling and testing if the pass criteria are not met. Visual and sensory inspection includes:

• Sight: look up, down, under, over, all around

• Touch: undersides, surfaces, equipment framework, etc., with white cloth or feel of films

Table 5.1: Overview of the various sampling sources

• Smell: off odours

• Turbidity of rinse waters

Tools can be used to facilitate the inspection, such as a torch (visible or UV light) and inspection mirrors. Tools are presented in table 5.2. Always consider the cross-contamination risk when using tools for inspection and clean and disinfect such tools between factories and between hygiene zones.

Visual inspection tools and test Advantages Disadvantages

Torch/flashlight (min 100 lumen, preferred 900 or up)

UV lamp (preferred 365 nm)

Inspection mirror (polished stainless steel)

Borescope

White cloth / gloves

Spray shadow test (visual or UV food grade dye)

Product dye test (food grade dye)

• Low costs

• Easy to use

• Low costs

• Easy to use

• Low costs

• Easy to use

• No equipment dismantling required

• Photo and video options

• Low costs

• Easy to use

• Immediate results

• Low costs

• Immediate results

• Enables easier visual inspection

Analytical Methods

Consider safety (personal protective equipment (ppe) may be needed)

• Can be costly

• Training recommended

Detection of small particles difficult

Table 5.2: Visual inspection tools

The analytical methods used to detect residuals or contaminants should be specific for the substance or the class of substances to be analysed (e.g. organic residue, chemical residue). Whichever method is used it should be validated and its limit of detection and quantification should be known. The specificity, sensitivity and reproducibility of the analytical methods should be suitable for purpose. If levels of contamination or residues are not detected, it does not mean that there is no residual contaminant present after cleaning. It means that the contaminants are not present in that specific sample or that they are present at levels lower than the detection limit of the analytical method.

Cleaning chemical residues can react with analytical methods to enhance or reduce the true detection value and to create false positive or negative results. Ideally, and for non-microbiological determinations, surfaces should be sampled after the cleaning chemical has been rinsed from the surface and before any disinfectant is applied.

If samples are taken after disinfection for non-microbiological analyses, and the disinfectant is not rinsed from the surface, it should be determined if the disinfectant residue influences the analytical test results.

If samples are taken after disinfection for microbiological analyses, a neutralisation step might be required to quench the disinfectant.

For all analytical methods, proper training and skilled personnel is required. The most common methods available are presented in table 5.3.

Contaminant detection

Analytical Method Sampling Advantages Disadvantages

Microorganisms Microbiological analysis

Organic residues Bioluminescence –ATP

Organic residues

Chemical residues

Chemical residues

TOC, Spectroscopy, HPLC, GLC

pH, Conductivity, Titration

Protein Total protein

Allergen protein ELISA

Allergen protein Dipstick (Lateral Flow Device - LFD)

Allergen protein DNA testing

Acceptance criteria

• Swab

• Sponge

• Contact plate

• Rinse medium

• Finished product

• Swab

• Rinse medium

• Finished product (for aseptic)

• Surface swab

• Rinse medium

• Surface swab

• Rinse medium

• Cleaning solution

• Surface swab

• Rinse medium

• Rinse medium

• Surface swab

• Finished product

• Surface swab

• Rinse water

• Surface swab

• Finished product

• Semi-quantitative

• Sensitive method

• Can be specific

• Quick result

• Automatic trending is possible

• Easy to use

• Sensitive and specific method

• Quick result

• Easy to use

• Real time monitoring

• Quick result

• Sensitive method

• Specific and sensitive method

• Quantitative method

• Quick result

• Specific and sensitive method

• Quantitative method

• No immediate results

• Not selective, not suitable for all soils

• Pass and fail levels must be defined for all sample locations

• Costly analytical equipment

• Qualified laboratory required

• Conductivity not suitable for all chemicals

• Not selective

• Not suitable for allergens

• No immediate results

• Costly

• Poor reproducibility

• Sensitive to false positive and false negative

• No standardised test

• Qualitative test only

• No immediate results

• Costly

• Not testing specific allergen protein

Table 5.3: Most common analytical methods

Pre-determined acceptance criteria for the level of cleanliness should be established before any testing is conducted. The acceptance limits should be defined according to the following criteria: specific, achievable, verifiable, and realistic. The acceptance limits should be determined based on a combination of the following parameters:

• Nature of the product

• Type of contaminant

• Sampling method

• Sampling location

• Analytical method

• Processing environment.

The acceptance criteria should be based on food safety requirements (pathogens, allergens) or product quality criteria (for example spoilage organisms, colour of the finished product, etc.). Either the approach for setting the limits should be product-specific or products should be grouped into families considering the worst-case product.

For sampling product contact surfaces, the criteria may be expressed as maximum limits for the amount of residual on the surface of the equipment after cleaning, for example:

• In µg/cm² for organic matter

• In CFU/cm² for microorganisms (CFU = colony forming unit)

• In nd/surface area for microorganisms, DNA or chemicals (nd = not detectable)

Acceptance criteria for allergenic material or toxins is typically the lowest amount of analysis below the limit of detection (LOD) or below the limit of quantification (LOQ) of the most sensitive available validated analytical method.

The criteria may also be expressed as the amount of residual in the ‘rinsing fluid’ after cleaning, for example:

• In µg/mL for organic matter or allergens

• In µg/mL for inorganic compounds (e.g. calcium)

• In µg/mL for detergent and/or disinfectant

• In CFU/mL for microorganisms

The amount of residual organic matter may also be expressed in terms of relative light units (RLU) when the ATP-method is used.

If acceptable limits are not met (soil, microorganisms, and cleaning agents), the performance of the cleaning as well as the disinfection should be investigated.

For criteria that are dependent on the food product, the cleanability of the equipment and the cleaning program (e.g TVC, ATP), an estimate of the desired criterion level, based on best practice, should be used as an acceptance criterion. This estimate can always be revised following the validation process and set as a target for subsequent cleaning monitoring/verification.

See also Annex B, Examples of Acceptance Criteria

Execution of the Cleaning Validation

To perform the validation tasks in a timely manner, there should be an appropriate system including organizational structure and documentation infrastructure, sufficient personnel and financial resources. Management and staff responsible for quality assurance should be involved. Personnel with appropriate qualifications and experience should be responsible for performing cleaning validations. If cleaning operations are outsourced, the personnel of the contractor should be involved in the validation process.

The execution of the cleaning validation against the previously defined validation protocol typically comprises a documentation review to verify that documents are current and complete and a physical walk through of the equipment to be cleaned and assessed.

Whilst the documentation review will not interfere with production schedules the assessment of the cleaned equipment may interfere, if dismantling and sampling is part of the protocol. Thus, enough shut down time to perform the job should be made available.

It is recommended to observe actual cleaning practices against the corresponding SOP as part of the cleaning validation to ensure that the SOP is followed Any sampling or monitoring devices, particularly on CIP sets, should be working and calibrated. Before the visual inspection and sampling is conducted, the cleaned equipment should be assessed for smell to confirm there are no traces of scale, odours, or chemicals.

The visual inspection post cleaning may include partial or complete disassembling of equipment with focus on anticipated hard to clean areas (‘hot spots’), for example valves, pumps, sensors, dead legs, etc. For large equipment, installations representative devices might be selected instead a complete tear down of the entire entity (e.g. valve arrangements for CIP). Taking photos will help to visualise findings.

Surface swabs should be taken only if all surfaces are visually clean.

Special consideration must be taken to ensure that recontamination from other sources than the equipment and cleaning process tested are avoided.

Cleaning Validation Report

The outcome of the cleaning validation should be documented and communicated using a standardised template for written reports, which may include the following content:

• Title, introduction, background and objective of the validation study

• Date of execution

• Names of persons involved in the study

• Equipment and processes validated

• Cleaning methods applied

• Summary and conclusion (pass/fail)

• Reference to the cleaning validation protocol

• Reference to relevant risk assessment for determining the selected worst case

• Procedures and test methods

• Cleaning programmes and cycles (CIP) examined

• Results

• Deviations & corrective actions

• Approval by authorized person in accordance with the plant’s Quality Management System, QMS (for example: approval by plant Quality Manager or designee)

All results should be recorded and archived in compliance with good data management practices.

The results obtained should be reviewed, analysed and interpretated against the pre-determined acceptance criteria.

For all deviations appropriate corrective and preventive actions (CAPA) should be defined. If deviations are accepted, this decision should be justified and documented (examples are provided in Annex D, E & F)

Revalidation

The requirements for revalidation should be determined using a risk-based, change management approach including a review of historical data, regarding monitoring and verification and maintenance programmes. Revalidation may be required after equipment, food process and cleaning program changes. Revalidation may be required, in particular after:

• Changes in the equipment

• Changes in the raw material (e.g. with different viscosity)

• Changes in the manufacturing process

• Changes in quality of utilities (e.g. steam, water etc.)

• Process line overhaul (shutdown and re-commissioning)

• Transfer of process lines

• Changes in cleaning procedures

• Changes in cleaning chemicals and parameters

• Production area or support system changes

• Appearance of negative safety or quality trends

• Appearance of new findings based on current knowledge and legislation

Changes should be controlled and documented through an appropriate change management program.

Monitoring

It is essential to monitor how effective cleaning is conducted over time, regardless of whether manual or automated methods are used. Whilst manual cleaning effectiveness may be difficult to monitor, automated systems will give many opportunities for data collection and recording. As opposed to verification, monitoring data shall ensure it can be responded to immediately by operators or the automated system, following any deviations relative to the validated SOP.

In general, monitoring may include:

• Number of cleaning operatives

• Handover from production operatives to cleaning operatives (e.g removal of materials, residues, etc.)

• Available time to perform the cleaning program

• Water quality

• Cleaning chemicals (type, concentrations)

• Temperatures

• Contact time for detergents and disinfectants

• Water/cleaning fluids (volume, flow, pressure)

• Cleaning tools (hygienic conditions, suitability)

• Draining/drying time

• Visual inspections

• Hygiene Monitoring (ATP, Lateral Flow Devices, protein swabs)

• pH

Some of the test methods have been discussed in section 5, Cleaning Validation Master Plan

Cleaning-In-Place (CIP) process steps and parameter values should be monitored throughout all cleaning steps. If these checks are not in place, the CIP may not perform in a controlled way, and reproducibility and efficacy are at risk. To have a controlled CIP process, monitoring of essential CIP parameters includes:

• Temperature

• Cleaning/disinfection chemical concentration

• Flow rate and pressure

• Time

The measurement of these parameters should be in-line; the advantage of in-line measurement is that it is in real time and the automatic control system or the operator can react in order to correct deviations. For tank cleaning it is recommended to also monitor spray devices to confirm that they are present and working.

When chemical concentrations cannot be measured in-line, the concentration should be monitored by chemical titration off-line.

Automated or semi-automated Cleaning-Out-of-Place (COP) systems, such as parts washers, cabinet washers and tray washers should have the feasibility to, at a minimum, monitor and record time, temperature and conductivity. For some systems, e.g. mold/crate washers, it is recommended to also monitor spray devices and the conveyor speed.

For manual COP and Open-Plant-Cleaning (OPC) operations monitoring activities might be limited to easy-toperform analytical checks on-site (e.g. pH, temperature, chemical titration) and visual controls.

Verification

Verification determines that the control parameters have been operating as intended. Cleaning verification often includes microbiological methods. Auditing is also a key verification activity to confirm that control practices have been undertaken correctly, have been recorded, and operators have been properly trained.

Verification activities should be established on a risk based approach. The risk assessment should highlight the key requirements to achieve a successful cleaning.

Verification may include:

• Trend analysis of monitoring results

• Allergen testing

• Microbiological testing

• Chemical residual testing

• Review of records

• Consumer complaint trends

• Adherence to SOP’s and work instructions (production, quality & maintenance staff)

• Results of internal and external audits

Some test and monitoring methods have been discussed in section 5 – Validation and section 6 – Monitoring. The acceptance criteria should be reviewed on a regular basis. as more information is obtained from routine cleaning verification. They may be modified as appropriate by changing the manufacturing environment, process, equipment or cleaning programme. A review of the acceptance criteria would also be required in case of changes in food product, process or cleaning programme (see 5.4 Revalidation).

Supplemental Reading

EHEDG Guidelines

Order information on EHEDG guidelines can be obtained under http://www.ehedg.org > Guidelines > Download & Order Information or use the link: https://www.ehedg.org/guidelines/download-order-information/

International and National Guidance

‒ Codex Alimentarius, Food Hygiene (Basic Texts)

‒ ISO 18593:2018 (en) Microbiology of the food chain - Horizontal methods for surface sampling

‒ ISO 22000 Food safety management systems - Requirements for any organization in the food chain (2018).

‒ FoodDrinkEurope: Guidance on Food Allergen Management for food manufacturers (2013)

International Audit Standards

‒ British Retail Consortium (BRC), Global Standard for Food Safety (2018)

‒ International Featured Standards (IFS), Food (2017)

‒ Safe Quality Foods (SQF) Code (Edition 8)

‒ Food Safety System Certification (FSSC) 22000

Annex A: Key Learning Points

• Cleaning is a pre-requisite for food safety and food quality and thus cleaning protocols should be validated, monitored and verified.

• Regulatory authorities, and other organizations such as Global Food Safety Initiative (GFSI) recognized standards require cleaning validation within food manufacturing.

• Validation, Monitoring, and Verification are not the same:

- Cleaning validation demonstrates that a cleaning procedure is effective in achieving the predetermined required level of cleanliness (Does it work?)

- Monitoring effectiveness is performed during each cleaning (real-time) to ensure the procedure is performed within specifications (Is it working?)

- Verification is performed during or after cleaning to determine that the control parameters have been implemented as intended (Has it worked?)

• Cleaning validation can be performed in three different ways: prospective, concurrent and retrospective cleaning validation.

• For a structured approach the development of a Cleaning Validation Master Plan is recommended, which comprises the Validation Protocol, the Execution of the Validation, the Cleaning Validation Report, and Revalidation requirements.

• The Validation Protocol defines the procedure on how the cleaning validation of a process or part of a process shall be done. It includes the number of repeats, referenced documents, selection of worst-case conditions, relevant contaminants, sampling and testing details, and acceptance criteria.

• For a successful execution of the Cleaning Validation, sufficient qualified personnel, financial resources, and time will be required. Typically, a validation comprises a documentation review, observations during cleaning, and a physical walk through of the process (visual inspection), followed by sampling and testing.

• The Cleaning Validation Report should be used to document and communicate the outcome of the cleaning validation. For any deviation appropriate corrective and preventive actions should be defined.

• Revalidations should be determined on a risk-based approach taking historical data of monitoring, verification, and maintenance activities into account. Changes to equipment, process and cleaning protocols may trigger the need for a revalidation.

Annex B: ATP threshold levels Establishing

ATP measurements are not suitable for all soils e.g inorganic soils. The results will also vary depending on the measuring device used. ATP equipment suppliers should provide guidance on establishing pass/fail criteria. However, the following factors should be considered:

‒ It is recommended that this procedure is done for a representative period of time to take into account changes in day to day operating procedures, different types of raw material or finished product and other production parameters.

‒ The ATP thresholds levels should be determined for each facility, each type of cleaning (routine cleaning, deep cleaning), and for each type of surface material. Age of surfaces may give different results.

‒ The surfaces that will be monitored for ATP must be visually clean as visible soil can inhibit the light signal.

‒ The surface must be properly rinsed after cleaning to ensure that cleaning detergents are removed before testing with ATP. Testing should be done after cleaning / before disinfection.

‒ The area swabbed should be standardised and appropriately large (typically 10 cm x 10 cm is recommended). Where smaller samples are taken (e.g inside of a pipe) the ATP threshold should be in proportion to the swabbed surface area.

‒ It is desirable for the same person to perform the testing during this phase, to avoid errors due to different swabbing techniques.

‒ To prevent rinse water background ATP delivering false results it is recommended that the ATP content in the rinse water is monitored prior to establishing pass/fail limits. In general, it is recommended to not perform ATP swabbing of areas that are not fully drained and where water has accumulated. A sufficient number of tests (typically 5-10) should be done by dipping ATP swabs into incoming potable water used for rinsing. The average RLU of the results should then be taken into account when determining the threshold values (e.g. by adding it as an instrument background level). Also, a negative control (unused swab) should be run.

‒ Negative controls tested with each set of sampling

The following steps should be performed:

a) Establish the baseline

b) Decide the target

c) Trend analysis

Each step is explained as follows:

a) Establish the baseline

For each clean the first step is to document the mean values that can be practically achieved. It is recommended to record data reflecting cleaning variables (repeated cleans, different surfaces/materials, different soiling, etc.) to get a baseline. As a rule of thumb 10 samples should be taken from each clean for at least 5 repeated cleans. Increased number of samples may be required, if initial results show high variability, e.g. between sampled areas.

During that time, cleaning should be performed according to the validated procedure and carefully monitored to truly represent normal cleaning.

…

b) Decide the target

When the baseline is known, the routine Pass/Fail criteria can be decided. The setting of the levels is a matter of judgement. Some sampling areas may require individual thresholds (e.g. different surface materials). Take the mean reading obtained for each threshold and add a comfort factor dependent on the variability of the baseline data (e.g. 3 x Sigma).

c) Trend analysis

It is recommended to continuously review the ATP measurement data and adjust threshold levels as needed Very high values of RLU after cleaning may not only indicate poor cleaning efficacy, but also hygienic design issues (e.g. worn out materials)

If high frequencies of Caution and Fail results are obtained with ATP monitoring, the SOP should be reviewed for ways to improve cleanliness. If low frequencies of Caution or Fail results are obtained, RLU limits could be reviewed and potentially lowered to maintain high standards and generate useful management data.

Annex C: Examples of Acceptance Criteria

Contaminant detection Test method Sampling Acceptance Criteria

Product residues

Micro-organisms

Torch/flashlight, UV lamp, Inspection mirror, Borescope,

White cloth/gloves

Spray shadow test

Product dye test

Microbiological analysis

Organic residues

Organic residues

Product residues

Chemical residues

Chemical concentration

Bioluminescence –ATP

TOC, NIR Spectroscopy, HPLC, GLC,

pH

Conductivity

Titration

Protein Total protein

Allergen protein ELISA

Dipstick

DNA testing

DNA

DNA testing

• Swab

• Sponge

• Contact plate

• Rinse medium

• Finished product

• Swab

• Rinse medium

• Finished product (for aseptic)

• Surface swab

• Rinse medium

• Surface swab

• Rinse medium

• Cleaning solution

Visual cleanliness (no visible residues) Absence of odours and films, and luminescence

Visual cleanliness, no residues on cloth/gloves

Visual cleanliness, absence of UV light reflection

Visual cleanliness, absence of dye

Criterion based on rinse water quality and microbiological risk assessment (e.g. TVC < 100 cfu / 100 cm2, or TVC < 100 cfu / swab, or TVC < 100 cfu / plate; TVC = Total Viable Count)

Criterion depending on device and background

To be determined during method development

pH of final rinse water is the same as pH of water used to rinse

Conductivity of final rinse water is the same as conductivity of water used to rinse

Alkaline and acid concentration not increased in comparison to rinse water quality

• Surface swab

• Rinse medium

• Rinse medium

• Surface swab

• Finished product

• Surface swab

• Rinse water

• Surface swab

• Finished product

• Surface swab

• Finished product

To be determined during method development

To be determined during method development

Criterion to be set based on risk assessment product and detection limit of method

To be determined during method development

Acceptance limit based on legal requirement of product carry-over of previous run (e.g. 1%) or customer demands

Annex D: Example of CIP Validation Protocol and Record

Validation Study -Summary

Title

Define your study

Introduction Explain the reason and the background why this validation should be done, and the hazards that need to be managed

Objective To pass the acceptance criteria

Factory Validation or Revalidation Indicate if this study is a validation for new installation or a revalidation due to change

Validation/Revalidation date

Scope

The date that validation/revalidation study completed

Description of the process or part of the process that shall be validated/revalidated (cluster processing groups where possible)

Products Indicate which product you choose and reason (products can be grouped, and worst-case product should be chosen)

Number of repeats Describe the number of successful validation/revalidation repeats based on the outcome of the risk assessment (see 5.1.1)

Results Pass or Fail?

Validation Team

Name

Responsibility

Validation Approval

Name

Job Title

Date

Signature

Team Leader Member Member Member Member

Referenced Documentation and Their Review for Qualification (see 5.1) (If need, documents can be attached in appendix)

Validation Input Requirements

Qualified Process (Doc. 34)*

Assessment of Process Equipment (legacy equipment)

Name and Issue Date

List relevant P&ID’s with names and issue dates

List relevant P&ID’s/documents with names and issue dates

Qualification (Yes/No.) and Date Remarks

List dates of qualification

List dates of assessment If no assessment data is available, a new assessment needs to be included.

List issues identified and e.g. if further dismantling is required

Qualified CIP Installation (Doc. 50 Annex C) *

Standard Operating Procedures (SOP) for the cleaning (and disinfection, if applicable)

Calibration records

Maintenance records

Analytical data of water quality (e.g. hardness, micro data, pH etc.)

Specifications of the chemicals used

Cleaning training records of staff

For revalidations: historical data of monitoring and verification activities (outof-limits situations and the completion of corrective actions).

List relevant P&ID’s with names and issue dates

List relevant SOPs with names and issue dates

List dates of qualification

List dates of review

Check if calibration is valid for all relevant equipment

Check if maintenance is done according to schedule

Check if all analytic data are according to specifications

Check if cleaning chemicals compliant with equipment specification and suitable for the application

Check the training records of staff performing cleaning operations

The last calibration date

Yes/No

Yes/No

Yes/No

*: If qualification evidence is not available, an evaluation should be performed to determine if and how the cleaning validation can proceed, e.g. carry out corrective action and identify critical sampling points.

Worst Case Scenario (see 5.1.2)

Identified Difficult to Clean Areas List and describe the most difficult areas to clean (e.g. photographs, or drawing, spray shadow test results)

Product In line with 5.1.2

Soiling condition

Cleaning parameters

Other relevant parameters

Scope of Validation Study

CIP Unit

Identification of CIP unit

Related to selected products, process conditions, locations and soil loading

least optimal temperature, cleaning agent concentration, time or flow

Object to be cleaned

List name of equipment

Report of Production Cycle

Product

Length of Production

Deviations or other events

Water Quality

Hardness

Microbiological data

pH

Conductivity

Cleaning Types

Cleaning Programme Yes/No Yes/No

Change-over cleaning

Midshift/Inter-mediate

Cleaning

End of production

Deep cleaning

Circuit/Loop

List here or indicate in P&ID about each segment of solution pipelines, product pipelines, and process equipment which are cleaned during an individual CIP cycle

Return

Pressure

Supply

Return

Pressure

Conductivity

Return

Pressure

Disinfection

Pressure

Relevant Contaminant, Sampling Plan, Test methods and Acceptance Criteria: (See 5.1.3, 5.1.4 and Annex B)

Remark: It is not recommended to conduct any analytical sampling and testing if the area is not visual clean

1. Manhole sealing of Tank A Product residue Total Inspection with the help of torch/flashlight, UV lamp, Inspection mirror etc. Photo

Visually clean without residues

2. Sieve before supply pump Product residue or particles Total Visual inspection, Photo Visually clean / free of particles Microbes

3. Shaft of mixing device Product residue Total Inspection with the help of light (UV or flashlight) Photo

Visually without residues

Visually clean without residues Residue Total Spray shadow test Visually clean, absence of UV light reflection n.d. Chemical residue (by pH) 10 cm pH Test strips 6-8 PAA residue 10 cm PAA Test strips ≤ 5 ppm Protein 10x10 cm Clean Card ≤50 µg/100 cm²

Odor Olfactory investigation Odour unremarkable

total

Inspection with auxiliary light (UV or flashlight) Photo visually without residues

Location xx (e.g. CIP return 1)

Chemical residue … ml

Chemical residue (by pH) … ml

Product residue … ml

organic residue (by COD) … ml

Total viable count (TVC)

ml

Enterobacteriac eae/ coliforms … ml

Photos of Surface Sample after Cleaning

Remark: Photos as example of successful cleaning

Sample

Sample 3

Location 3:

Sample 4

Surface tension test e.g. Camphor test

Rotation crystals

pH Test strips 6-8

Visual inspection No particle, clear colourless

Photometry ≤ 15 mgO2/L

TVC analysis TVC ≤ 100 cfu/ml

Positive/negativecontrol with lactose-Peptone Bouillon

n.d. in 100 ml

Surface Sample

Note: After “opening” the system was then cleaned and disinfected again.

(photos)

Sample 1: <Location>

Sample 2: <Location>

Sample 2: <Location>

Sample 3: <Location>

Rinse Water/Product Test

Rinse

Rinse water 2

Enterobacteriaceae ≤ …cfu/g

Final product TVC ≤ …cfu/g

Entero n.d.

List of Corrective Actions (if applicable)

Validation Comments (Observations, deviations, etc.)

Appendix:

Analytical Methods / Devices : Method SOP/Device Remark

Visual inspection UV light

TVC SOP xxx

Enterobacteriaceae/ coliforms SOP xxx

Protein: SOP

Peracetic acid: Test strip of ……

Allergen Lab xxxx

Reference Documents Attachment

Certification….

Annex E: Example of OPC Validation Protocol

and Record

Validation Study -Summary

Title

Introduction

Objective

Factory

Validation or Revalidation

Validation/Revalidation date

Scope

Products

Number of cleaning operators

Available cleaning window

Define your study

Explain the reason and the background why this validation should be done, and the hazards that need to be managed

To pass the acceptance criteria

Indicate if this study is a validation for new installation or a revalidation due to change

The date that validation/revalidation study completed

Description of the process or part of the process that shall be validated/revalidated (cluster processing groups where possible)

Indicate which product you choose and reason (products can be grouped, and worst-case product should be chosen)

Indicate how many operatives were involved in the clean

Indicate the total amount of cleaning time

Number of repeats Describe the number of successful validation/revalidation repeats based on the outcome of the risk assessment (see 5.1.1)

Results Pass or Fail?

Validation Team

Name

Responsibility

Validation Approval

Name

Job Title

Date

Signature

Team Leader Member Member Member Member

Referenced Documentation and their review for qualification (see 5.1) (If need, documents can be attached in appendix)

Validation Input Requirements

Qualified Process Equipment (new installed equipment)

Assessment of Process Equipment (legacy equipment)

Name and Issue Date

List relevant P&ID’s with names and issue dates

List relevant P&ID’s/documents with names and issue dates

Qualification (Yes/No.) and Date Remarks

List dates of qualification

List dates of assessment If no assessment data is available, a new assessment needs to be included.

List issues identified and e.g if further dismantling is required

Qualified OPC Installation/equipment*

Qualified Automated OPC Installation/equipment*

Standard Operating Procedures (SOP) for the cleaning (and disinfection, if applicable)

Calibration records

Maintenance records

Analytical data of water quality (e.g. hardness, micro data, pH etc.)

Specifications of the chemicals used

Cleaning training records of staff

For revalidations: historical data of monitoring and verification activities (outof-limits situations and the completion of corrective actions).

List relevant P&ID’s with names and issue dates, e.g. types of cleaning satellites, nozzles, guns and hoses

List relevant P&ID’s with names and issue dates, e.g. types of cleaning satellites, nozzles, guns and hoses

List relevant SOPs with names and issue dates

List dates of qualification

List dates of qualification

List dates of review

Check if calibration is valid for all relevant equipment

Check if maintenance is done according to schedule

Check if all analytic data are according to specifications

Check if cleaning chemicals compliant with equipment specification and suitable for the application

Check the training records of staff performing cleaning operations

The last calibration date

Yes/No

Yes/No

Yes/No

*: If qualification evidence is not available, an evaluation should be performed to determine if and how the cleaning validation can proceed, e.g. carry out corrective action and identify critical sampling points.

Worst Case Scenario (see 5.1.2)

Identified Difficult to Clean Areas List and describe the most difficult areas to clean (e.g. photographs, or drawing, spray shadow test results)

Product In line with 5.1.2

Soiling condition Related to selected products, process conditions, locations and soil loading

Cleaning parameters least optimal temperature, cleaning agent concentration, chemical contact times, pressure and flow, distance between nozzle and surface

Other relevant parameters

data

Cleaning Types

Cleaning Programme Yes/No Yes/No

Change-over cleaning

Midshift/Inter-mediate

Cleaning

End of production

Deep cleaning

OPC

Pre

Detergent

Post

Disinfection -

Remark:

641debe25f64e16796825305bea53f23a601f51817c979e448fb2ca

Remark: It is not recommended to conduct any analytical sampling and testing if the area is not visual clean

6. Filler A Product residue Total Inspection with the help of torch/flashlight, UV lamp, Inspection mirror etc. Photo

Visually clean without residues

7.

8. Product residue Total Inspection with the help of torch/flashlight, UV lamp, Inspection mirror etc. Photo

Visually clean without residues Microbes ATP Swab and ATP test ≤ xx RLU

visually without residues Personal copy of: Pieter de Haan, pdehaan@stonhard.com, 24.03.2023 19:28:50, IP: 189.244.53.247

Photo of Surface Sample after Cleaning

Remark: Photos as example of successful cleaning

Sample 1

Location 1: e.g. Filler A

Sample 2 Location 2: <Photo> <Photo>

Sample 3 Location 3: Sample 4 Location 4: <Photo> <Photo>

Surface Sample

Note: After “opening” the system was then cleaned and disinfected again.

Visual Inspection Results (photos)

Sample 2: <Location>

Sample 2: <Location>

List

of Corrective Actions (if applicable)

Validation Comments (Observations, deviations, etc.)

Appendix:

Analytical methods / devices:

Method SOP/Device

Visual inspection UV light

TVC SOP xxx

Enterobacteriaceae/ coliforms SOP xxx

Protein: SOP

Peracetic acid: Test strip of ……

Allergen Lab xxxx

Reference Documents Attachment

Remark

Certification….

Annex F: Example of COP Validation Protocol and Record

Validation Study -Summary

Title

Define your study

Introduction Explain the reason and the background why this validation should be done, and the hazards that need to be managed

Objective To pass the acceptance criteria

Factory

Validation or Revalidation

Validation/Revalidation date

Scope

Indicate if this study is a validation for new installation or a revalidation due to change

The date that validation/revalidation study completed

Description of the process or part of the process that shall be validated/revalidated (cluster processing groups where possible)

Products Indicate which product you choose and reason (products can be grouped, and worst-case product should be chosen)

Number of cleaning operators

Indicate how many operatives were involved in the clean

Available cleaning window Indicate the total amount of cleaning time

Number of repeats Describe the number of successful validation/revalidation repeats based on the outcome of the risk assessment (see 5.1.1)

Results Pass or Fail?

Validation Team

Name

Responsibility

Validation Approval

Name

Job Title

Date

Signature

Team Leader Member Member Member Member

Referenced Documentation and their review for qualification (see 5.1) (If need, documents can be attached in appendix)

Validation Input Requirements

Qualified Process Equipment (new installed equipment)

Assessment of Process Equipment (legacy equipment)

Name and Issue Date

List relevant P&ID’s with names and issue dates

List relevant P&ID’s/documents with names and issue dates

Qualification (Yes/No.) and Date

List dates of qualification

Remarks

List dates of assessment If no assessment data is available, a new assessment needs to be included.

List issues identified and e.g. if further dismantling is required

Qualified COP Installation/equipment *

Qualified Automated COP Installation/equipment *

Standard Operating Procedures (SOP) for the cleaning (and disinfection, if applicable)

Calibration records

Maintenance records

Analytical data of water quality (e.g. hardness, micro data, pH etc.)

Specifications of the chemicals used

Cleaning training records of staff

For revalidations: historical data of monitoring and verification activities (outof-limits situations and the completion of corrective actions).

List relevant P&ID’s/documents with names and issue dates, e.g. COP sink, bin washers etc.

List relevant P&ID’s with names and issue dates, e.g. automated COP bath, tunnel washer etc.

List relevant SOPs with names and issue dates

List dates of qualification

List dates of qualification

List dates of review

Check if calibration is valid for all relevant equipment

Check if maintenance is done according to schedule

Check if all analytic data are according to specifications

Check if cleaning chemicals compliant with equipment specification and suitable for the application

Check the training records of staff performing cleaning operations

The last calibration date

Yes/No

Yes/No

Yes/No

*: If qualification evidence is not available, an evaluation should be performed to determine if and how the cleaning validation can proceed, e.g. carry out corrective action and identify critical sampling points.

Worst Case Scenario (see 5.1.2)

Identified Difficult to Clean

Areas List and describe the most difficult areas to clean (e.g. photographs, or drawing)

Product In line with 5.1.2

Soiling condition Related to selected products, process conditions, locations and soil loading

Cleaning parameters Least optimal temperature, cleaning agent concentration, times, pressure and flow

Other relevant parameters Refreshment rate of cleaning bath, nozzle blockage, nozzle missing and positioning

Scope of Validation Study

List the Objects to be cleaned

Water Quality

Hardness

Microbiological data

Conductivity

Chemical

Detergent/disinfectant

Name

Midshift/Intermediate Cleaning

End of production

Deep cleaning

COP Verification: Cleaning Parameters

Pre Rinse

Detergent - <Chemical

Acid Cycle - <Chemical

Post Rinse

Disinfection - <Chemical

Final Rinse

Remark: It is not recommended to conduct any analytical sampling and testing if the area is not visual clean

Total viable count (TVC) 10x10 cm Swab and TVC analysis ≤ 100 cfu / 100 cm2 Personal copy of: Pieter de Haan, pdehaan@stonhard.com, 24.03.2023 19:28:50, IP: 189.244.53.247 641debe25f64e16796825305bea53f23a601f51817c979e448fb2ca

1.

residue

with the help of torch/flashlight, UV lamp, Inspection mirror etc. Photo

2. Filler Nozzle Product residue or particles Total Visual inspection, Photo Visually clean / free of particles

Visually clean without residues Microbes ATP Swab and ATP test ≤ xx RLU n.d.

Visual

Photo of Surface Sample after Cleaning

Remark: Photos as example of successful cleaning

Sample 1

Location 1: e.g. Hose

Sample 2

Location 2: <Photo> <Photo>

Sample 3

Location 3:

Sample 4 Location 4: <Photo> <Photo>

Surface Sample

Note: After “opening” the system was then cleaned and disinfected again.

Visual Inspection Results (photos)

Sample

Sample 2: <Location>

Sample 2: <Location>

List of Corrective Actions (if applicable)

Validation Comments (Observations, deviations, etc.)

Appendix:

Analytical methods / devices: Method SOP/Device Remark

Visual inspection UV light

TVC SOP xxx

Enterobacteriaceae/ coliforms SOP xxx

Protein: SOP

Peracetic acid: Test strip of ……

Allergen Lab xxxx Certification….

Reference Documents Attachment