Cleaning validation is an important process in the pharmaceutical industry to ensure product safety and purity. It involves documenting evidence that an approved cleaning procedure will adequately clean equipment used in pharmaceutical production. The cleaning validation process includes planning, execution, analytical testing, and reporting phases. A cross-functional team plans the validation program, which involves grouping products, equipment, cleaning agents, and methods. Sampling techniques like swab and rinse sampling are used in the execution phase. Acceptance criteria are established and analytical tests are performed on samples to verify cleaning levels. A validation report documents the results and conclusions to obtain approval. Revalidation may be required if any changes are made to the cleaning process.

1. CLEANING VALIDATION IN
PHARMACEUTICAL INDUSTRIES
Guided by : Dr.S.S.Mahajan
Prepared by : Shweta Sambhaji Shelke
Quality Assuranace(3rd sem)
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2. 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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3. 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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4. Planning
phase
Execution
phase
Analytical
testing
phase
Reporting
phase
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5. PLANNING PHASE
CLEANING
VALIDATION
TEAM
CLEANING
VALIDATION
PROGRAM
PERSONNEL
TRAINING
CLEANING
PROCESS
PLAN
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6. Validation
team
members
:
Validation
officer
Production
department
officer
Packaging
department
officer
Maintance
department
officer
(utilities/calib
ration/HVAC
)
Quality
control
department
officer
Quality
assurance
department
officer
Product
development
laboratory
officer
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7. RESPONSIBILITIES OF TEAM MEMBERS
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8. • Coordinating entire team
• Monitoring process
• Compiling data
• Preparing final reports
Validation
officer
• Prepare SOP’s for new
process or equipment
• Assist in collection of
validation data
Production
department
officer
• Prepare SOP’s for the
cleaning of new packaging
• Assist in the collection of
validation data
Packaging
department
CLEANINGVALIDATIONTEAM
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9. • Defining requirements.
• Training
• Informing relevant departments
Maintenance
department
• Perform microbiological testing
• Provide data for active ingredient and
cleaning agent
Quality control
department
• Reviewing & approving the validation
• Assessment in case of deviations
Quality
assurance
department
• Defining the process to be validated
• Provide technical assistance
Product
development
laboratory
CLEANINGVALIDATIONTEAM
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10. CLEANING
VALIDATION
PROGRAM
1.
PRODUCT
GROUPING
2.
EQUIPMENT
GROUPING
3.
CLEANING
AGENT
GROUPING
4.
CLEANING
METHOD
GROUPING
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11. PRODUCT GROUPING
Worst case product
Least soluble Most toxic
Highest
cocentration
Others
Subdivide it
Formulation Process
Selection of product
Low & high risk
drugs
Solid & liquid
dosage
Soluble & insoluble
ingredients
Sterile & nonsterile
facilities
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12. EQUIPMENT GROUPING
Can implement C V procedure
Small scale Large scale
Subdivide into
Dedicated &
Non dedicated
Minor & Major
Noncritical &
Critical site
Non product &
product contact
Equipment train
:single &
complex
Equipment selection
Design function
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13. Cleaning
agent
grouping
Equipment
grouping
Product
formulation
Select type
such as acid &
base
cleaning
method
grouping
Automated
and manual
cleaning
Clean in place
and clean out
of place
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14. 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 14

15. Cleaning
process
Solvent
cleaning
Ultrasonic
Vapor
degreasing
Hot water
extraction
Aqueous
cleaning
Manual
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16. ULTRASONIC CLEANING
 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.
Principle Image
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17. ULTRASONIC CLEANING
Separates the liq and microscopic
void
Creates compression wave in liq
U.S.Waves fluid changing size &
Ultrasound generating transducer built
into chamber
In a ultrasound chamber
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18. VAPOR DIGRESSING
 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 eupment .
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19. HOT WATER EXTRACTION
 It is a typical
cleaning
method that
uses a
combination of
high water
pressure for
agitation, and
hot water to
increase
reaction rate.
surface is dried to avoid surface saturation
lower the pH of the fibers to a neutral state.
use an acetic acid solution
surface is thoroughly rinse out the preconditioner
light agitation with a grooming brush
preconditioning of the soiled surface with an alkaline agent
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20. Execution
phase
Sampling
Swab
sampling
Rinse
sampling
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21. SWAB SAMPLING
The extract examined by a suitable analytical
method
By adding it to dilution solvent
The swab is extracted
A small area of the cleaned equipment is swabbed
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22. SWAB SAMPLING
 Dissolves & physically
remove sample
 Adaptable to wide
variety of surfaces
 May allow sampling of
defined area
 Applicable to active ,
microbial & cleaning
agent residue
 An invasive technique
that introduce fiber
 Complex & hard to
reach complex areas
Advantages Disadvantages
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23. RINSE SAMPLING
 In 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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24. RINSE SAMPLING
 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
Advantages Disadvantages
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25. ANALYTICAL TESTING PHASE
 Accuracy
 Precision
Repeatability
Intermediate
 Specificity
 LOD
 LOQ
 Linearity
 Range
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26. 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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27. 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 27

28. 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 . 28

29. 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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30. CONCLUSION
 Cleaning 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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31. REFERENCES
 S.I.Haider ,E.S .Asif , “Cleaning validation manual
,a comprehensive guide for pharmaceutical
&biotechnogy industries:”,CRC Press
publication,page no -1-30.
 Active pharmaceutical ingredients committee
,“Guidance on aspects of cleaning validation in
active pharmaceutical ingredient plants”,december
2008
 Andrew walsh , “cleaning validation for 21st
century :the overview of new ISPE cleaning guide
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32. REFERENCES
 S.W.Harder , “validation of cleaning processes”
pharmaceutical technology.(1984)
 Sudha T., Krishana Kanth , Nukala Poorana
Chandra Sainath1, Mishal1, Saloman Raja ,
Ganesan , “Method Development and Validation-
A Review”, Journal of Advanced Pharmacy
Education & Research (2012)
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33. THANK YOU
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