CLEANING METHOD DEVELOPMENT

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. 1 A Seminar as a part of curricular requirement for I year M. Pharm II sem i ster . Presented by Mr P.Venkatesh. (Reg. No. 20L81S0714 ) D e p a r tment o f P h a r maceutical A n a l y sis CLEANING METHOD DEVELOPMENT

2. 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 CONTENTS

3. 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. 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. 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. 6 Level of cleaning The equipment usage - dedicated use or not . The stage of manufacturer - early, intermediate and final stages. The nature of potential contaminants - toxicity ,solubility. Above three steps must be evaluated based on the next product

7. 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. 8 Level of cleaning differ from each other 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. 9 Surfactants anions and non ions used as components for detergent. ca tion 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. 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. 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. 12 Cleaning mechanism Mechanism totally depend on selection of Cleaning agent and type of residue to be cleaned. Method involved in cleaning of residue are Dissolution - solubility of residue in cleaning agent . Eg : SLS ,chelating agents. Saponiation agent - breakage of ester bond in fatty acids and glycerol which is soluble in water . Eg : NaoH Wetting agent - lower surface tention of cleaning solution so that it can easily penetrate into solution. Eg : Surfactants

13. 13 Sampling method Two methods of sampling Swabbing method : This method is most commonly used and involved taking of inert material on the end of the probe and rubbing it methodically across the surface. The swab are added with dilution solvent and these solvents are analyzed by suitable analytical instrument.

14. 14 Rinse sampling: A measured area of cleaned surface is rinsed or solvent washed and solvent is collected and tested for traceses of contaminants . Continuation ...

15. 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. 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. 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. 18 S.W.Harder , "The validation of cleaning process , " Pharmaceutical technology.8(5),29- 34 (1984) J.A.smith , " A modified swabbing Techniques for validation of detergent residue in clean in place system , "pharmaceutical technology. 16(1),60-66(1992) Mc cormick,P.Y and Cullen L.F., in pharmaceutical process validation, 2 nd edition., 319-349(1993) Richard Forsythe; Equal hold time for cleaning validation; pharmatimes vol-4 no-6,june-2008 Reference

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