cleaning validation in pharmaceutical industries

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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