Lifecycle Approach to Cleaning Validation

LIFECYCLE APPROACHC C O CTO CLEANING VALIDATION

Paul L. Pluta, PhD

Validation Week EU, 2013

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MANUAL CLEANING -- Do you really know what is happening?

Q to operator: “Why is there so much foam in the tub?”A: “I put in extra soap because the equipment was really dirty.”

Q to operator: “Why is there powder on the (clean) equipment?”A: “No problem -- We’ll get the residue when we set up ”A: No problem -- We ll get the residue when we set up.

Q to operator: “Why don’t you follow the cleaning procedure?”Q to operator: Why don t you follow the cleaning procedure?A: “The cleaning procedure really doesn’t work.”

ABOVE NOT ACCEPTABLE – TRAINING NEEDED

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Q to operator: “Why is there powder on the clean equipment?”p y p q pA: “It’s clean enough.”Q to QA (equipment inspection person): “Did you approve that the equipment

is clean?”A: “It’s clean enough.”Q to management: “Do you know that your equipment is not clean?”A: “It’s clean enough.”

Q to operator: “You cleaned the gasket with pure soap – this is not the procedure? Also it is dangerous – these are corrosive chemicals.”

A: “That is the only way to get it clean.”Q: “So why don’t you tell someone to change the procedure?”A: “We don’t have time.”


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Q to management: “Did you finish cleaning the equipment? We are here to swab for cleaning validation.”

A ( dl ) “W l d th i t th ti th tA (very proudly): “We cleaned the equipment three times so that we won’t have any problems.”

Q to validation person: “Did you know that the manufacturing people always clean the equipment multiple times before it is swabbed?”

A: “Sure, we knew.Q: “Why didn’t you stop this?”A: “These people are our friends. We have to work with these people.”


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OUTLINEOUTLINE

Lifecycle Approach Applied to Cleaning ValidationStage 1 ActivitiesStage 1 Activities• Cleaning Method Development• Analytical Method Development• Site equipmentStage 2 Activities• Cleaning documentation• Validation conformance lotsStage 3 Activities• Maintaining Validation• Change Control• Management review• Management review

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OBJECTIVESOBJECTIVES1. Application of lifecycle approach to cleaning

validation2. Cleaning lifecycle stage details

• Process development and understanding• Process qualification• Maintaining the validated stateg

3. Cleaning validation problems• Global experiences

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Lifecycle Approach to Cleaning Validation –Value? Does this make sense?Value? Does this make sense?

• Cleaning is a process

• Validation lifecycle concepts being applied to equipment, facilities, utilities, computers, etc., by validation and technical expertsp

• Who can argue with understanding, performing, and maintaining the validated state?g

• Consistent with QbD and ICH approaches

• Lifecycle approach (i.e., understanding, performing, maintaining) vs. traditional approach – Which would you rather present to an auditor?you rather present to an auditor?

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WHAT IS THE CLEANING PROCESS?Cleaning Process Performance Qualification (PPQ)

A t t d CIP S tAutomated CIP System

Process steps QualificationProcess steps Qualification1. Residue on equipment Equipment2. Water procedure Purified Water3 Cleaning agent procedure Computer / software3. Cleaning agent procedure Computer / software4. Water procedure Compressed air5. Purified Water procedure Conductivity analysis6. Dry TOC analysisy y

Equipment is clean -- Process is validated

Process parameters Quality attributes

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WHAT IS THE CLEANING PROCESS?Cleaning Process Performance Qualification (PPQ)

M l Cl iManual Cleaning

Process steps QualificationProcess steps Qualification1. Residue on equipment Personnel2. Water rinse Purified Water3 S b ith l i t C d i3. Scrub with cleaning agent Compressed air4. Water rinse5. Scrub6. Water rinse7. Purified Water rinse8 Dry8. Dry

Equipment is clean -- Process is validated

Process parameters Quality attributes9

CLEANING VALIDATION OVERVIEW1990 t1990s present

1. Defined cleaning procedure (SOP) – basis?g p ( )2. Product A batch does not contaminate subsequent

Product B batch3. Acceptance limit calculated4. Assume uniform contamination of all equipment5 Three conformance lots = Validated cleaning procedure5. Three conformance lots = Validated cleaning procedure6. Validated analytical method (original API)7 Worst-case matrix approach7. Worst case matrix approach

One-time event

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FDA PROCESS VALIDATION GUIDANCELIFECYCLE APPROACH TRANSITIONLIFECYCLE APPROACH TRANSITION

APPPLICATION TO CLEANING VALIDATION

Pre LifecyclePre Lifecycle

Cleaning development (?) PQ change control

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Lif l A hLifecycle Approach

Development PQ MaintenanceEXPANDED SCOPE OF VALIDATION

INCREASED SPECIFIC STAGE REQUIREMENTSINCREASED SPECIFIC STAGE REQUIREMENTS

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LIFECYCLE APPROACH TO CLEANING VALIDATION

Scientific and technical approachDesign and development

– Residue + cleaning agent + cleaning procedure Clean equipment

Performance demonstrationMonitoring and maintenanceRationale, responsibility, and accountabilityRationale, responsibility, and accountabilityFuture process improvements

Not the following:St d d it th d ( b i ti l )– Standard site method (no basis or rationale)

– Personnel driven (no control)– “Do whatever it takes” (high variation)– SOP (no accountability)– Validation (?) – One-time event.

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STAGE 1, PROCESS DESIGN (PROCESS UNDERSTANDING)APPLICATION TO CLEANING

FDA Guidance Topics1. Building and capturing process knowledge and understanding.2. Establishing a strategy for process control.

Application to CleaningUnderstand residue chemistry (solubility, stability) Determine cleaning agent based on residue chemistryDetermine cleaning agent based on residue chemistryDetermine cleaning process• Identify sources of variability• Establish methods to control variabilityEstablish methods to control variability

– Process Analytical Technology

Rational analytical method and supporting worky pp gCharacterization of equipment to be cleaned and supporting workTrained sampling personnel

DOCUMENT ALL OF THE ABOVE13

DEVELOPMENT (STAGE 1)CLEANING PROCESS DEVELOPMENTCLEANING PROCESS DEVELOPMENT

• Physical and chemical properties of the residue is basis for cleaning processprocess

• Considerations for determination of most difficult-to-clean residue• Residue solubility and stability in determining worst-case soils

Residue chemistry critical for analytical method• Residue chemistry critical for analytical method• Cleaning agent chemistry consistent with residue chemistry• Cleaning process chemistry and engineering and consistent with

residue and cleaning agent.

RESIDUE CHEMISTRY– BASIS FOR CLEANING PROGRAM– BASIS FOR ANALYICAL METHOD

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RESIDUE PROPERTIES -- BASIS FOR CLEANING PROCESS

Case study: Antibiotic suspension containing insoluble API (base)

Original cleaning method: Water, PurW, dry• No documented cleaning validation for many yearsNo documented cleaning validation for many years• Unknown peaks on original cleaning validation attempts• API insoluble

Second method: Alkaline soap wash water PurW drySecond method: Alkaline soap wash, water, PurW, dry• Unknown peaks again• API insoluble

Fi l th d A id h lk li h t P W dFinal method: Acid wash, alkaline soap wash, water, PurW, dry• No residues• Unknown peaks determined to be degradants and flavors.

API di l ( id b t li ti )• API dissolves (acid-base neutralization)

Consider active drug and other residue chemistry in development of cleaning processof cleaning process

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DETERMINATION OFMOST DIFFICULT TO CLEAN RESIDUEMOST DIFFICULT TO CLEAN RESIDUE

BASIS FOR CLEANING PROGRAM

Water solubility – USP Tables• Is this adequate? NO!pH effect – API with ionizable groups?Solubility in cleaning agent?

• Determine solubility at range pH 1-12• Understand solubility at pH of cleaning liquidUnderstand solubility at pH of cleaning liquid• Understand solubility in cleaning agent liquid

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pH SOLUBILITY PROFILE, pH 1-12p SO U O , p

Solubilitymg/ml

Drug A

Drug B

pH 1 7 12

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RESIDUE SOLUBILITY AND STABILITY FOR DETERMINING WORST CASE SOILSDETERMINING WORST-CASE SOILS

Solubility considerations• Hydrophilic and hydrophobic molecules• Ionization – Effect of pH

Eff t f t t• Effect of temperature• Surface active molecules• Liquid and semisolid product vehicle polarityLiquid and semisolid product vehicle polarity

Stability considerationsHydrolysis oxidation photolysis physical changes• Hydrolysis, oxidation, photolysis, physical changes

What residue is really present?Consider chemistry of residues

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CLEANING MATRIXDetermine Worst-Case Soil

SOLUBILITY (mg / ml)H 1 W t H 12 Alk lipH 1 Water pH 12 Alkaline

Cleaning AgentDrug A 25 25 25 25

Drug B 15 15 15 15

Drug C 5 5 150 250Drug C 5 5 150 250

Drug D 150 10 10 50

Drug E 125 10 100 250

Consider acid cleaning agent for drugs D and E

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WORST CASE CLEANING

Determination of worst-case cleaning based on API toxicity, worst-case dose, etc.on API toxicity, worst case dose, etc.– Standard calculation

Cleaning procedure may be based onCleaning procedure may be based on excipients having greatest effect on cleaningcleaning– Hydrophilic polymers

D– Dyes– Hydrophobic vehicles

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BIOTECH CLEANING CHEMISTRY -- APIProtein molecules degrade in alkaline conditionsDegradation rate is milder in acidic conditionsgDegradation rate increases with temperatureAPI residues typically consist of protein fragments and

aggregatesAnalytical method: Non-specific analysis

Reference: Kendrick, Canhuto, and Kreuze. Analysis of Degradation Products of Biopharmaceutical API Caused g pby Cleaning Agents and Temperature. Journal of Validation Technology, V15, #3, Summer 2009.

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BIOTECH CLEANING CHEMISTRY – GROWTH MEDIUM

Medium Composition• Acids or bases• Monovalent salts• Monovalent salts• Polyvalent salts• Amino acids• Proteins (polypeptides)• Carbohydrates• Aqueous soluble organicsq g• Non-aqueous soluble organics

Consider medium composition at end of cycle.

Reference: Azadan and Canhoto. A Scientific Approach to the Selection of Cleaning Validation Worst-Case Soils for Biopharmaceutical manufacturing. Cleaning and Cleaning Validation, Volume 1. 2011.Cleaning and Cleaning Validation, Volume 1. 2011.

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CLEANING CHEMISTRY MECHANISMS

• Wetting• Emulsification• Dispersion• Solubilityy• Chelation• OxidationOxidation• Hydrolysis

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CLEANING AGENT OPTIONS

• Water• Commodity alkalis and acidsy• Organic solvents• Surfactants

– Anionic– Cationic– Amphoteric– Nonionic

• Formulated detergents

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COMPONENTS OF FORMULATED DETERGENTS

• Surfactants• Alkalis• Acids• Sequestrants / chelants• Dispersants / anti-redeposition agents• Corrosion inhibitors• Corrosion inhibitors• Oxidizing agents• Enzymes• Buffers / builders• Preservatives

MUST HAVE CONTROL OF CLEANING AGENTHAVE CONFIDENTIALITY AGREEMENT WITH SUPPLIER

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CLEANING ENGINEERINGFactors affecting cleaning• Soil residueSoil residue

– Soil levels, soil condition, hold times, soil mixing, water quality and residue,

• Cleaner and parameters (TACT)– Time, Action, Concentration, Temperature– Others

• Surface and equipment design

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CLEANING PROCESSSOURCES OF VARIATIONSOURCES OF VARIATION

• Cleaning agent preparation – must be exact• Automated cleaning vs. manual cleaning• Manual cleaning process variation• Human physical strength variation• “Cleaning” between same-product batches in g p

campaign – residue level build-up• Campaign length – residue level build-up• Time to initiate cleaning (dirty hold time)• Residue chemical and physical changesp y g

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EQUIPMENT TO BE CLEANEDCleaning-related qualification• Product-contact materials• Compatibility with cleaning agents• Surface areas – need for residue calculations

E i t i l• Equipment equivalence• Most-difficult-to-clean locations on equipment -- Highest

risk locations for samplingrisk locations for sampling• Non-uniform contamination equipment• Non-uniform contamination sampling locationsg• Sampling methods (swab / rinse)

Part of IQ/OQ/PQ for manufacturing equipment

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PROCEDURE TO DETERMINE SAMPLING LOCATIONSLOCATIONS

Specific documented procedure recommendedSpecific documented procedure recommended• Equipment technical evaluation• Observation of equipment after processingObservation of equipment after processing• Equipment disassembly review• Cleaning procedure review• Cleaning procedure review• Equipment evaluation review• Operator interviews• Operator interviews

SOP describing aboveDocumentation of above for equipment sampling

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TIME TO INITIATE CLEANING“DIRTY HOLD TIME”DIRTY HOLD TIME

1. Make Product A2 Cl2. Clean3. Make Product BHow long between end of #1 and start #2?Is residue same? Does residue change?Wh h h id ?What can happen to the residue?• Wet and dry processes

• Chemical changes (hydrolysis oxidation etc )• Chemical changes (hydrolysis, oxidation, etc.)

• Physical changes

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CAMPAIGN LENGTH

How many lots in manufacturing campaign before cleaning must be done?cleaning must be done?

What about “cleaning” between batches?What about cleaning between batches?• Equipment should be visually clean

Terminology: “Between lot procedure”• Terminology: Between lot procedure• How much residue “build-up?”

DO NOT IDENTIFY AS “BETWEEN LOT CLEANING”

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MANUAL CLEANING

• Manual cleaning procedures should be monitored and maintained with increased scrutiny compared to non-manual procedures

• More frequent training of cleaning personnel• Increased supervision• Periodic (annual?) revalidation batches

Manual cleaning is high riskManual cleaning is high risk

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ANALYTICAL METHOD DEVELOPMENT

Early stage 1 (development) analysis –validation not required but must be soundvalidation not required but must be sound

Validated method when used for Stage 2 cleaning validation and post validationcleaning validation and post-validation testing (change control)

All methods and data (including stage 1) subject to regulatory auditregulatory audit

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Analytical method must measure actual residue –what residue is actually present on equipment surfaces?

• Small molecules– API– API degraded – specific or non-specific method

Bi t h l l• Biotech molecules– API degraded – non-specific method

UNDERSTAND RESIDUE CHEMISTRY

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Cleaning agent residue• Analytical method to determine residual cleaning

agent.• Information from cleaning agent vendor

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ANALYTICAL METHOD DEVELOPMENTR t diRecovery studiesCan sampling procedure adequately recover residue

from equipment surfaces?from equipment surfaces?• Product contact materials• High % of total surface area• Obtain representative coupons from equipment

fabricatorsHi h ( 80%) t it i• High (e.g., >80%) acceptance criteria

• Factor may be used in calculation– Multiple approachesMultiple approaches– Factor every calculation?

All sampled surfaces must have recovery dataAll sampled surfaces must have recovery data

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SAMPLINGSampling methodsSampling methods• Sampling (swab) critical activity• Training programTraining program• Trained sampling personnel

– Demonstrated acceptable performance

• Documented training and retraining• Worst case compounds / procedures in training

– Volatile solvents (importance of rapid technique)– Volatile solvents (importance of rapid technique)

• Worst case sampling equipment– Extension poles

• Retraining considerations– Who does sampling? Personnel skills

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SAMPLING TRAINING

Sampling is extremely critical to cleaning validation programvalidation program

Inadequate sampling = false negativeInsufficient pressure on surface– Insufficient pressure on surface

– Swab solvent evaporationI ffi i t l d– Insufficient area sampled

Auditors routinely ask for sampling program training methods and training records

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STAGE 2, PROCESS QUALIFICATION –(VALIDATION PERFORMANCE)APPLICATION TO CLEANINGAPPLICATION TO CLEANING

1. Design of a facility and qualification of utilities and equipment2. Process performance qualification3. PPQ protocol4 PPQ t l ti d t4. PPQ protocol execution and report

Qualification of equipment, utilities, facilities• Cleaning equipment (CIP)

Process Performance Qualification (PPQ) – commercial scaleConclusion that process consistently produces clean equipmentConformance batches• All support systems, documents, training, personnel, etc. in place• Target / nominal operating parameters within design space• Additional testing (swab / rinse)• Decision to “release cleaning process” for routine commercial useDecision to release cleaning process for routine commercial use• Post validation monitoring plan – Based on risk

– Drug residue properties– Manual or CIP

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CLEANING EQUIPMENTCLEANING EQUIPMENT

CIP system must be qualified (IQ/OQ/PQ or ASTMCIP system must be qualified (IQ/OQ/PQ or ASTM E2500)

Riboflavin (or other) coverage testing( ) g gTemperature controlsFlow rates etcFlow rates, etc.PAT inline systems

– Drug disappearance – spectrophotometry, other methodsg pp p p y– Cleaning agent rinse -- conductivity

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CLEANING PROCEDURE DOCUMENTATION (Cl i B t h R d)(Cleaning Batch Record)

SOPFill t k h lf f ll• Fill tank half full

• Add half scoop of soap• Scrub as needed• Rinse until clean• Re-scrub and re-rinse if needed

CLEANING PROCEDURE RECORD• Fill tank with 500 L water. Sign/date __________• Add 20.0 kg cleaning agent. Sign/date __________• Disassemble Part A. Steps 1,2,3,4,5• Scrub for 20 minutes. Sign/date __________• Disassemble Part B. Steps 1,2,3,4,5• Soak Part B in cleaning liquid for 10 minutes. Sign/date __________• Rinse Part A and Part B with 50 L water. Sign/date __________• Rinse with 50 L Purified Water. Sign/date __________• Dry with compressed airy p

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CLEANING PROCEDURE RECORD• Fill tank with 500 L water. Sign/date __________• Add 20.0 kg cleaning agent. Sign/date __________• Disassemble Part A. Steps 1,2,3,4,5p• Scrub for 20 minutes. Sign/date __________• Disassemble Part B. Steps 1,2,3,4,5• Soak Part B in cleaning liquid for 10 minutes. Sign/date __________g q g __________• Rinse Part A and Part B with 50 L water. Sign/date __________• Rinse with 50 L Purified Water. Sign/date __________• Dry with compressed airy p

KEY POINTSExact concentration of cleaning agent liquidExact concentration of cleaning agent liquidSignature on quantitative stepsGrouping non-quantitative steps (e.g., disassembly)

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VALIDATION REQUEST / PLANInitiates cleaning validation• New cleaning validation or change control process

i timprovements• Strategy and approach• Scientific and technical basis• Scientific and technical basis• Specify required protocols and other work to accomplish

validation• Risk-based• References: Stage 1 Design / development reports

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VALIDATION PROTOCOL

Cleaning validation protocols and other work as specified in Validation Planas specified in Validation Plan– Risk based

Include sampling pages indicating worstInclude sampling pages indicating worst case sampling locations.

S if t it iSpecify acceptance criteria

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VALIDATION RESULTS / REPORT

Test results as required in validation protocol.• Discussion Consistency with Stage 1• Discussion. Consistency with Stage 1

development work.• Clear statement the cleaning process is (or isClear statement the cleaning process is (or is

not) validated.• Recommendations for Stage 3 monitoring andRecommendations for Stage 3 monitoring and

maintenance. – Additional limited testing based on data and risk– Routine monitoring based on risk

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STAGE 3, CONTINUED PROCESS VERIFICATION(VALIDATION MONITORING AND MAINTENANCE)

APPLICATION TO CLEANINGActivities to assure process remains in validated stateChange control -- evaluate impact of change and validate (test) as g p g ( )

necessaryTrend and assess data

– PAT rinse timesConductivity data– Conductivity data

Study OOS and OOT (Out of Trend) dataImprove processImprove control to detect and reduce variabilityImprove control to detect and reduce variabilityCleaning non-conformances and deviationsRe-validation – definition: Actual batch or “paper”• Is re-testing necessary?• When should re-testing be considered?Periodic Management Review• Documentation reviewed by management

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• Documented review

POST-VALIDATION MONITORING AND MAINTENANCE

1. Stage 2 specific requirements– Additional testing based on actual data– Ex: One location has high (acceptable result)

2. Routine monitoring and maintenance2. Routine monitoring and maintenance– Risk based

3 Change control program3. Change control program

CHANGE CONTROL MOST IMPORTANT ANDCHANGE CONTROL MOST IMPORTANT AND DIFFICULT TO ADMINISTER

PERSONNEL MUST RECOGNIZE “CHANGE”PERSONNEL MUST RECOGNIZE CHANGE

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POST-VALIDATION MONITORING AND MAINTENANCE

Residue toxicity risk• Residue that can be visually seenResidue that can be visually seen

– Room lighting must be adequateProvide additional lighting if necessary– Provide additional lighting if necessary

• Residue that cannot be visually seeny– Swab after each batch?

CONSIDER PATIENT RISK AND COMPANY RISK

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CHANGE CONTROLCHANGE CONTROL

• All associated personnel must be aware of h t lchange control

• Change control system developed• Process improvements expected based on

ongoing experienceP i t h ld b l t d b• Process improvements should be evaluated by technical people (i.e., Stage 1)St 2 PPQ d t d h i t• Stage 2 PPQ conducted when appropriate based on Stage 1 technical evaluation.

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POST-VALIDATION MONITORING

Periodic review of cleaning performance• Deviations• Deviations• Non-conformances (dirty equipment)

R l i• Re-cleaning• Change control

O h i i (CIP d )• Other monitoring (CIP data)• Product APR data• Statistical Process Control data treatment• Management review -- documented

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CLEANING DOCUMENTATION• High level documents• Specific cleaning validation documents

– Design/Development, performance, monitoring/maintenance

• Specific cleaning validation support documents (equipment qualifications)

• Cleaning validation approach documents (Worst case matrix, g pp ( ,calculations, sampling locations, etc.)

• Production documents (Cleaning Procedure Records)– Production cleaning policiesg p

• Management review documents• Associated documents

– Personnel training in direct and associated areasPersonnel training in direct and associated areas – HR records

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CLEANING DOCUMENTATIONHigh level documents• Corporate policy• VMP (Cleaning VMP)Stage 1 documents

Cl i d l t t• Cleaning process development report• Analytical method development report• Supporting equipment documents (materials, surface areas, equivalent equipment,

sampling, etc.)p g, )Stage 2 documents• Validation PPQ request, protocol, results• Cleaning equipment qualification• Cleaning procedure recordStage 3 documents• Change control documents • Process monitoring• Process monitoring• Management review

CONSISTENT LIFECYCLE STRATEGY AND APPROACHCONSISTENT LIFECYCLE STRATEGY AND APPROACH

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SUMMARYSTAGE 1 DESIGN AND DEVELOPMENTSTAGE 1 -- DESIGN AND DEVELOPMENT

INCLUDING COMMON PROBLEMS

Understanding cleaning process• Residue properties

– Residue degradationResidue degradation• Rational cleaning process based on residue• Scientific and technical cleaning matrix U d t d d t l f i tiUnderstand and control sources of variation• Dirty hold time• CampaignsRational analytical method based on residue propertiesEquipment to be cleaned characterized• Worst case samplingWorst case sampling

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SUMMARY – EQUIPMENT TO BE CLEANEDINCLUDING COMMON PROBLEMSINCLUDING COMMON PROBLEMS

• Equipment characterization• Equipment characterization• Residue calculations• Materials of product contact• Materials of product contact• Surface areas

W t f li b d i k• Worst-case areas for sampling based on risk– Non-uniform contamination

Equivalent equipment• Equivalent equipment

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SUMMARY – ANALYTICALINCLUDING COMMON PROBLEMSINCLUDING COMMON PROBLEMS

Understand residue• Solubility and stability• Validated analytical method for actual residue

– Specific or non-specific analytical methods– Specific or non-specific analytical methods

• API and cleaning agent residue

Recovery studies from product contact materials• API and cleaning agent

Swab / rinse testing on equipment • Most difficult to clean sampling sitesMost difficult to clean sampling sites• Use of auxiliary sampling equipment (extension pole)

Swab / rinse training of sampling personnel

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SUMMARYSTAGE 2 – PERFORMANCESTAGE 2 – PERFORMANCE

INCLUDING COMMON PROBLEMS

Cleaning Process Conformance LotsCleaning equipment qualifiedCleaning equipment qualifiedCleaning procedure specified (Not SOP)Cleaning documentationCleaning documentation

– Request– Protocol– Results / Report

Manual cleaning – high risk

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SUMMARYSTAGE 3 MAINTAINING VALIDATIONSTAGE 3 -- MAINTAINING VALIDATION

Change control evaluate impact of changeChange control -- evaluate impact of change and validate (test) as necessary

Improve processImprove processImprove control to detect and reduce

variabilityyCleaning non-conformances and deviationsPeriodic Management Reviewg

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CLEANING AND CLEANING VALIDATIONCLEANING AND CLEANING VALIDATIONFor the Pharmaceutical and Medical Device

I d t iIndustries

V1 Basics Expectations and PrinciplesV1. Basics, Expectations, and Principles V2. Applications of Basics and Principles

V3 Lifecycle Approach to Cleaning ValidationV3. Lifecycle Approach to Cleaning Validation (Expected end 2013)

Paul L. Pluta, PhD, editor

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PAUL L PLUTA PhDPAUL L. PLUTA, PhDEditor-in-Chief

Jo rnal of Validation TechnologJournal of Validation TechnologyJournal of GXP ComplianceAdvanstar Communications

Adjunct Associate ProfessorUniversity of Illinois at Chicago (UIC) College of PharmacyChicago, IL, USA

Pharmaceutical industry experiencey p

Contact: [email protected]

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Health & Medicine

Lifecycle Approach to Cleaning Validation