the cleaning validation process - learnaboutgmp · pdf file16 cleaning process standard...
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The Scope of Cleaning Validation
The Cleaning Validation Sequence
Prerequisites
Cleaning Validation Strategy, Plan, and Policy
Sampling
Recovery Studies
Analytical Method Selection andDevelopment
Analytical Method Validation
Acceptance Criteria
Validation Master Plan
Cleaning Validation Plan
Cleaning Method Development
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The Cleaning Validation Process
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Cleaning Process Standard Operating Procedures (SOPs)
Cleaning Validation Protocols
Protocol Execution
Clean and Dirty Hold Times
Validation Report
Post Validation Monitoring
Maintaining the Validated Status
Retrospective Cleaning Validation
Glossary
What You Learned
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Normally, only cleaning procedures for surfaces of the equipment that
come into contact with product need to be validated.
To be more effective, however, programs for the elimination of cross-
contamination must also address non-product contact surfaces. When
establishing prerequisites for non-product contact surfaces, you must
review the probable interactions of those areas.
Cleaning validation is usually only needed for critical cleaning, e.g.
between manufacturing of one product and a different product and is not
normally necessarily for non-critical cleaning such as between batches of
the same product (or different lots of the same intermediate in a bulk
process).
In API manufacturing, it may be unnecessary to validate equipment
cleaning where residues are removed by subsequent purification steps.
Products that simulate the physiochemical properties of the substance to be
removed may be used instead of the substances themselves, where such
substances are toxic or hazardous.
The intervals between use and cleaning, as well as cleaning and reuse,
The Scope Of CleaningValidation
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should also be validated. Cleaning intervals and methods should be
determined.
It is the responsibility of the manufacturer to demonstrate that the level
of cleaning and validation performed is adequate based on each individual
situation and on a justifiable scientific rational.
Microbiological aspects should be considered, although they should
consist largely of preventative measures rather than the removal of
contamination once it has occurred. (WHO)
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The CleaningValidation Sequence
Cleaning ValidationStrategy
Process & ProductDevelopment
Validation MasterPlan
Cleaning Agents &Methods Identified
Cleaning MethodDeveloped
Sample techniqueand Methods of
Detection identified
Establishment ofAcceptable Levels
of Carry-over
Analytical MethodsIdentified /Developed
Analytical MethodsValidated
Recovery StudiedCompleted
RefiningAcceptable Levels
of carry-Over
Cleaning SOPsCreated
ValidationSummary Report
Revalidation
Execution ofProtocol
Cleaning ValidationProtocol
Cleaning VP
CLEANING VALIDATION PROCESS(Prospective)
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Before beginning cleaning validation, the following should be available
and completed:
· Agreed company strategy and policy;
· Cleaning methodology;
· Defined sampling methodology;
· Completed analytical method selection / development;
· Validation of analytical methods;
· Defined acceptance criteria;
· Validation Master Plan;
· Cleaning Validation (Master) Plan;
· Creation of related SOPs;
· Cleaning Validation Protocol.
Pre-requisites
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The cleaning validation policy should incorporate the following:
· A statement specifying what company policy is on validation of
cleaning procedures related to equipment (including ancillary) and
processes, such as:
Cleaning only after product changeover or between batches in
campaigns;
Cleaning of major and minor equipment;
· Company policy on the dedication of all equipment for each
product, (if products are deemed too dangerous and / or highly
active to manufacture on multi-product equipment);
Company policy on the grouping of products or equipment such as:
Validate the cleaning of each product individually;
Bracketing / grouping products for cleaning validation;
Bracketing / grouping equipment for cleaning validation;
Selection of “worst case” products;
· Sampling Methodology to be used;
· Analytical validation policy;
· The rational for the methods by which acceptance criteria is
Cleaning ValidationStrategy, Plan & Policy
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determined;
· Revalidation policy;
Glossary / Definition of terms employed during validation (for
example, rinse, flush, wash and so on).
Campaign Production and Batch Production
Campaign production always helps in minimizing cross-contamination
issues between lots. In a multiple-product facility, campaign lots of a single
product or product family are produced in the same equipment. At times,
the production run may be stopped for a partial cleanup of the equipment,
which is less stringent than a full cleanup. Once the campaign production is
over, an intensive cleaning of the facility and equipment can be performed
before starting production of a different product.
Minor and Major Equipment
Although there is no such terminology as “minor” equipment in current
good manufacturing practices (cGMPs), items such as utensils may be
regarded as minor equipment.
Major equipment represents those that play a central role in
production processes. Typically, the cleaning of major equipment will be the
subject of specific standard operating procedures (SOPs) and it is important
to differentiate those pieces of equipment that are central to the production
process from those that perform a secondary role (utensils).
An Easy to Understand Guide | Cleaning Validation