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

15

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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18

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