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Cleaning validation in pharmaceutical

industries

Prepared by : Deepak Kumar Pharmaceutics dept.(M-Pharm-1st Year)

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Definition Cleaning validation – It is a documented

evidence which provides high degree of assurance that an approved cleaning procedure will provide equipment that is suitable for processing of pharmaceutical products for API.

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Importance of cleaning validation Cleaning validation is heart of pharmaceutical

activity

Related to safety and purity of the product Level of cleanliness is achieved by cleaning

procedure which depend upon its cleaning validation method if performed confidently ,method produces reproducible results .

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Planning phase

Execution phase

Analytical testing phase

Reporting phase

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Planning phase

CLEANING VALIDATION TEAM

CLEANING VALIDATION PROGRAM

PERSONNEL TRAINING

CLEANING PROCESS

PLAN

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Validation team

members :

Validation officer

Production department

officer

Packaging department

officer

Maintance department

officer (utilities/calibration/HVA

C)

Quality control

department officer

Quality assurance

department officer

Product development laboratory

officer

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Responsibilities of team members

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Validation officer

•Coordinating entire team •Monitoring process•Compiling data•Preparing final reports

Production departmen

t officer

•Prepare SOP’s for new process or equipment•Assist in collection of validation data

Packaging departmen

t

•Prepare SOP’s for the cleaning of new packaging•Assist in the collection of validation data

C

LEAN

ING

VAL

IDAT

ION

TE

AM

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Maintenance department

• Defining requirements. • Training

• Informing relevant departments Quality control

department • Perform microbiological testing • Provide data for active

ingredient and cleaning agent

Quality assurance

department

• Reviewing & approving the validation

• Assessment in case of deviations

Product development laboratory

• Defining the process to be validated

• Provide technical assistance

CLE

ANIN

G V

ALID

ATIO

N T

EAM

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CLEANING VALIDATIO

N PROGRAM

1.PRODUCT

GROUPING

2.EQUIPMEN

T GROUPING

3.CLEANING

AGENT GROUPING

4.CLEANING METHOD

GROUPING

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Product grouping

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Equipment grouping

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Cleaning agent grouping

Equipment grouping

Product formulation

Select type such as acid & base

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Personnel training Why it is required ?

To understand selection of cleaning parameters such as time , temperature , cleaning agent concentration ,sheeting , rinsing .

To evaluate step for removal of residue by following /understanding SOP’s

Therefore in cleaning validation this is also adds the same value as other considerations

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Cleaning process

Solvent cleaning

Ultrasonic

Vapor degreasing

Hot water extraction

Aqueous cleaning

Manual

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Ultrasonic cleaning Principle Image A process that uses

ultrasound(20-400kHz)& appropriate cleaning solvent or water

Time require for cleaning generally3-6nmin & may exeed to 20 min depend upon object to be clean.

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Vapor degreasing Surface finishing process .Uses the solvent in the form of vapor to clean work

piece. Used where water based cleaning is impracticable .After boiling of solvent it enters the fill line & uses

spray technique to clean equipment .

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Hot water extractionIt is a typical cleaning method that uses a

combination of high water pressure for agitation, and hot water to increase reaction rate.

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Swab sampling

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Swab samplingAdvantages DisadvantagesDissolves & physically

remove sampleAdaptable to wide

variety of surfacesMay allow sampling of

defined area Applicable to active ,

microbial & cleaning agent residue

An invasive technique that introduce fiber

Complex & hard to reach complex areas

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Rinse samplingIn rinse sampling API

equipment will be cleaned by several washing cycles (runs ) OR cycles/runs

Outline - amount of residue remaining in the equipment after cleaning based on the amount of residue in the last run of the routinely used cleaning procedure.

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Rinse samplingAdvantages Disadvantages Allow the sampling of

large surface area Allow the sampling of

unique (porous) surfaces Applicable for

actives ,cleaning agent & exipients

Inability to detect location of residue

Usually use for rinsing an entire piece of equipment

Excess of rinsing sample is required

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Acceptance criteria Establishing acceptance limit

Samples should be practical , achievable ,and verifiable

NMT 10ppm of any product will appear in other product

NMT 0.1% therapeutic dose of any product will appear in maximum daily dose of the following

product

No quantity of residue should be visible on the equipment after cleaning procedure are performed

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Reports A validation report is necessary to present the

results & conclusions with approval page duly signed off by corresponding signatories depicting the approval of validation study.

It should include :• Summary of procedures used to clean ,

sample ,test • Physical & analytical test results• Conclusion regarding acceptability of results • Recommendations based on result • Review of protocol deviation • Interim reports till complete study

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Documentation The cleaning process should be documented n an SOP

Documentation should be in such a way that following information is readily available:

The area or piece of equipment cleaning

The person who carried out the cleaning

When the cleaning was carried out

The SOP defining the cleaning process

The product which was previously processed on the

equipment being cleaned .

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Revalidation It is done if :• Cleaning procedure is changed • Raw material are changed • Change in formulation • New detergents • Modification of equipment

To avoid this regular checking is done.

The production manager ,QC manager , QA manager & whole validation team decide revalidation is necessary or not .

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ConclusionCleaning validation is heart of

pharmaceutical industry .

If the proper cleaning is not contamination may occur in the product & whole process of formulation hampered by this.

Whole team distribute their work for attending the cleaning validation process to which QA officer gives approval based on the overall documented evidances.

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References:- Google

Slideshare

Industrial Pharmacy ‘’Lachman and Liberman”

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Thank you