Cleaning Validation

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

6. Validation
team
members
:
Validation
officer
Production
department
officer
Packaging
department
officer
Maintance
department
officer
(utilities/cali
bration/HVA
C)
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
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CLEANINGVALIDATIONTEAM

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 deviationsQuality assurance
department
• Defining the process to be validated
• Provide technical assistance
Product
development
laboratory
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CLEANINGVALIDATIONTEAM

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
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15. Cleaning
process
Solvent
cleaning
Ultrasonic
Vapor
degreasing
Hot water
extraction
Aqueous
cleaning
Manual
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16. 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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17. 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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18. 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.
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19. 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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20. Swab sampling
Advantages Disadvantages
 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
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21. 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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22. Rinse sampling
Advantages 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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23. 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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24. 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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25. 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 . 25

26. 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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27. 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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28. References:-
 Google
 Slideshare
 Industrial Pharmacy ‘’Lachman and Liberman”
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29. Thank you
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