In this slide contains Introduction, levels of cleaning, mechanism, sampling method of cleaning validation. Presented by: P. VENKATESH (Department of pharmaceutical analysis).RIPER, anantapur

1. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 1
A Seminar as a part of curricular requirement
for I year M. Pharm II semister.
Presented by
Mr P.Venkatesh.
(Reg. No. 20L81S0714)
Department of Pharmaceutical Analysis
CLEANING METHOD
DEVELOPMENT

2. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 2
• Introduction
• Tips for cleaning method development
• Level of cleaning.
• Types of Cleaning agents.
• Mechanism of cleaning agent
• Sampling techniques
• Analytical method
• Establishment of acceptance limit
• Reference

3. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 3
Cleaning method development
• Cleaning method development is a continuous progress in
parallel with evaluation of drug
Method development consist of three main stages:
Feasibility- determine if the method will work with your sample.
Development- where optimised method.
Validation- where optimised method is validated.
Introduction

4. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 4
Tips for cleaning method
development
• Selection of cleaning process: manual verses automated.
• Cleaning data from the past as difficult to clean any product.
• Our strategy for the cleaning as a process.
• Worst case should be selected that is hard to clean.
• Determination of temperature of water and cleaning agent.
- volume of water to be used for cleaning.
- contact time of cleaning agent.

5. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 5
Continuation
• Selection of cleaning agent and its concentration that can clean
the residue.
• Recovery factor to determine analysis of product and detergent
residue
• A proper validated analytical method should be selected according
to nature of product and cleaning agent.
• sampling location should be selected considering hard to clean
place.

6. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 6
Level of cleaning

7. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 7
Continuation
Levels Attributes
Cleaning
validation
Level 0
Batch to batch cleaning in
an identical process
Not required
Level 1
Change over between
intermediate of one product
to final intermediate of
another product
Required but not
necessary
Level 2 Change over from one API
to another API
Essential

8. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 8
Continuation
Parameters Level 0 Level 1 Level 2
Risk Low Moderate High
Acceptance
limits
High Moderate Low
Degree of
cleaning
Less expensive
More
expensive
Much
expensive
Verification
Visual
inspection
Not required
Analytical
testing
required

9. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 9
• Surfactants
• anions and non ions used as components for detergent.
• cation and amphoteric used in the formulation of
disinfectants their microcidal effect.
• Complexing agents - Complexing with minerals and
inorganic components.
• Sequestering agents - EDTA.
• Anti foaming agent - mineral oil, vegetable oil.
• Oxidizing agent - hydrogen peroxide .
Types of cleaning agents

10. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 10
Cleaning process
• Includes four stages
STAGE-1
Determination of most appropriate cleaning
Procedure for equipment
Develop and validate the sampling and choose analytical method for
the compound being cleaned
Evaluate equipment surface and determine

11. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 11
STAGE-2
Develop a cleaning validation protocol for the product and
equipment being cleaned.
STAGE-3
Generate a time cleaning validation report on clean by clean
basis.
STAGE-4
Generate a cleaning validation report details and acceptance
of cleaning procedure for product and equipment.
Continuation

12. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 12
Cleaning mechanism

13. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 13
Sampling method

14. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 14
Continuation ...

15. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 15
• The analytical method should be validated before cleaning
validation is performed.
• The method chosen should detect residues and contaminants
specific for the substance should be analyzed
• Validation of analytical method should include
• Precision
• Linearity
• Accuracy
• Limit of detection
• Limit of quantification
• Ruggedness
• Robustness
Analytical method

16. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 16
• Method selected should be specific and sensitive.
Specific and non specific methods
• Specific methods -Detects unique compounds in the presence of
potential contaminants Eg:HPLC
• Non specific method -detects any compounds that produce
response Eg:pH and conductivity
• Other methods
• Thin layer chromatography: determination of surfactants.
• atomic absorption spectroscopy: determination of inorganic
contaminants
Continuation ...

17. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 17
• The acceptance limit established for contaminant level in the
sample should be practical, achievable and verifiable.
• NMT 10 ppm of any product will appear in another product.
• No quantity of residue should be visible on the equipment after
cleaning process are performed.
• For certain allergic ingredients the limit should be below limited of
detection.
Establishment of acceptance
Limits

18. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 18
1. S.W.Harder, "The validation of cleaning process, "Pharmaceutical
technology.8(5),29- 34 (1984)
2. J.A.smith, " A modified swabbing Techniques for validation of
detergent residue in clean in place system,"pharmaceutical
technology. 16(1),60-66(1992)
3. Mc cormick,P.Y and Cullen L.F., in pharmaceutical process
validation, 2 nd edition., 319-349(1993)
4. Richard Forsythe; Equal hold time for cleaning validation;
pharmatimes vol-4 no-6,june-2008
Reference

19. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 19