Cleaning validation SlideShare presentation
- 1. 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 CLEANING VALIDATION Presented by: Name: B.S. Preethi Guided by: Course: M. Pharmacy 1st year Dr. K. Vinod Kumar M.Pharm Ph.D Reg no: 24L81S0705 Associate Professor Dept: Pharmaceutical Analysis
- 2. 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 Contents: Introduction Cleaning validation Cleaning method development Validation of analytical method Cleaning of equipment Cleaning of facilities Cleaning in place Conclusion References
- 3. 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 Introduction: Validation: In the pharmaceutical industry, validation is a documented process that provides high assurance that a specific process will consistently produce a product meeting predetermined quality standards. It's a crucial aspect of ensuring product safety, efficacy, and regulatory compliance.
- 4. 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 Cleaning Validation: Cleaning validation is a documented process that provides evidence that a cleaning procedure consistently removes product residues, cleaning agents, and microbial contaminants from equipment to acceptable levels, ensuring the quality and safety of subsequent products. It's a critical part of current Good Manufacturing Practice (cGMP) in the pharmaceutical industry and is essential for preventing cross-contamination and maintaining product integrity.
- 5. 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 Cleaning Validation:
- 6. 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 Types of Cleaning: 1.Manual Cleaning – Done by operators using brushes, water, detergents. 2. Clean-in-Place (CIP) – Automated cleaning without dismantling equipment. 3. Clean-out-of-Place (COP) – Equipment parts are dismantled and cleaned separately.
- 7. 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 Types of contamination: 1. Cross contamination with active ingredients: Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated. 2. Contamination with unintended materials or compounds: While inert ingredients used in drug products are generally recognised as safe for human consumption , the routine use, maintenance and cleaning of equipments provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents.
- 8. 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 3. Microbial contamination: Maintenance, cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment. Steps involved in cleaning validation: 1.Planning phase 2. Execution phase 3. Analytical testing phase 4. Reporting phase
- 9. 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 Levels of cleaning: Level-1:It is used only between steps in the same manufacturing process. Level-2:It is used when cleaning between steps in the same manufacturing. Level-3:It is performed when cleaning after an intermediate or final productor one product in preparation of an intermediate step of another product. Level-4:It would be used after final product is ready.
- 10. 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 Analytical method validation: Analytical method validation ensures the reliability of methods used to detect and quantify residues on equipment after cleaning. It involves demonstrating that the chosen analytical technique (e.g., HPLC, TOC) is suitable for its intended purpose and provides accurate, precise, and reliable results. This validation process is crucial for demonstrating that cleaning procedures effectively remove residues to acceptable levels, safeguarding product quality and patient safety.
- 11. 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 Key aspects of analytical method validation in cleaning validation: Specificity: The method should be able to accurately identify and measure the target residue without interference from other substances, including cleaning agents. Linearity: The method's response should be directly proportional to the concentration of the residue within the specified range. Range: The method should be able to accurately measure residues within a defined range relevant to the cleaning process.
- 12. 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 Precision: The method should provide consistent results when repeated multiple times under the same conditions. Accuracy: The method should accurately reflect the true amount of residue present. Limit of Detection (LOD) and Limit of Quantification (LOQ): These parameters define the lowest concentrations of residue that can be reliably detected and quantified, respectively. Common Analytical Techniques: High-Performance Liquid Chromatography (HPLC): Widely used for separating and quantifying residues, often with UV or mass spectrometry detection.
- 13. 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 Common Analytical Techniques: Total Organic Carbon (TOC) Analysis: Measures the total amount of organic carbon, providing an overall assessment of cleanliness, though it doesn't identify specific residues. Spectrophotometry (UV-Vis): It Can be used for detecting and quantifying residues that absorb UV or visible light. Swab Technique: A common sampling method in cleaning validation, where swabs are used to collect residue samples from equipment surfaces.
- 14. 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 Sampling Methods: Methods are used to verify the effectiveness of cleaning procedures by detecting and quantifying residual substances on equipment surfaces. The primary methods include: swab sampling (direct surface sampling) and rinse sampling (indirect sampling). Visual inspection is also a crucial part of the process, providing immediate feedback on cleaning deficiencies. 1. Swab Sampling: This method involves wiping a defined area of the equipment surface with a swab (a piece of absorbent material on a stick) that has been pre-wetted with a suitable solvent. The swab is then analyzed to detect and quantify any residues present.
- 15. 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 Swab sampling is particularly useful for assessing the cleanliness of hard-to-reach areas and for quantifying residues on specific surfaces. It's a direct method, meaning it assesses the surface itself for cleanliness. 2. Rinse Sampling: Rinse sampling involves rinsing a specific area of the equipment with a solvent and then analyzing the rinse solution for any residues. This method is suitable for assessing the cleanliness of large surface areas or inaccessible areas that cannot be swabbed directly. It is an indirect method, as it assesses the cleanliness of the surface by examining the rinse solution that has come into contact with it. Rinse samples can be particularly useful for detecting residues that may not be easily soluble or that are trapped within equipment components.
- 16. 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 Acceptance criteria: 1.Chemical determination: 1. Nmt 0.1% of the normal therapeutic dose of any product will appear in the maximum daily dose of subsequent product. 2. Nmt 10 ppm of any product will appear in another product. 3 . For certain allergic ingredient penicillin, cephalosporin, steroid and cytotoxic , the limit should be below the limit of detection. 2. Physical determination: No quantity of residue should be visible on the equipment after cleaning procedure are performed. 3. Microbial contaminant: Total aerobic count : 1. Bacterial count: NMT 20 CFU. 2. Molds : NMT 02 CFU.
- 17. 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 Determination of MACO(Maximum Allowable Carry Over): MACO = TDD previous x MBS SF x TDD next Where, MACO : Maximum allowable carry over TDD previous: Standard therapeutic dose of investigated product. TDD next: Standard therapeutic dose of the daily dose of the next product. MBS: Minimum batch size for the next product. SF: Safety factor( Normally1000 is used in calculation based on TDD)
- 18. 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 Cleaning of Equipment: Cleaning of equipment is a critical process in the pharmaceutical industry to ensure product quality, patient safety, and regulatory compliance. It involves the removal of product residues, cleaning agents, microbial contaminants, and other impurities from manufacturing equipment. Why Cleaning is Important: Prevents cross-contamination between different products Ensures compliance with Good Manufacturing Practices (GMP) Maintains product quality and efficacy Protects patient safety Avoids regulatory penalties
- 19. 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 Cleaning of Equipment:
- 20. 20 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. Pre-cleaning: Remove visible residue 2. Washing: Use water and cleaning agents. 3. Rinsing: Remove detergent traces. 4. Drying: Air-dry or use hot air to avoid microbial growth. 5. Inspection: Visually check and/or test for cleanliness. 6. Documentation: Record all cleaning steps and results. Steps Involved in Equipment Cleaning:
- 21. 21 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Cleaning Agents Used: Water (Purified Water, WFI) Detergents (acidic, alkaline, neutral) Disinfectants (alcohol, hydrogen peroxide)
- 22. 22 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Clean in place: Clean-In-Place (CIP) is a method of cleaning the interior surfaces of equipment like pipes, vessels, reactors, and tanks without disassembly. It is widely used in the pharmaceutical, biotechnology, and food industries to ensure hygiene and prevent contamination.
- 23. 23 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Clean in Place:
- 24. 24 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 What is CIP? CIP is an automated cleaning method where cleaning solutions (like water, detergents, or sanitizers) are circulated through equipment systems to remove product residues, microorganisms, and contaminants. Steps in CIP Process: 1. Pre-Rinse: Removes loose residues with water 2. Detergent Wash: Uses alkaline or acidic detergents to break down soils 3. Intermediate Rinse: Removes remaining detergent and loosened dirt 4. Sanitization / Disinfection (if needed): Kills any remaining microorganisms. 5. Final Rinse :Removes sanitizer and prepares the system for next use.
- 25. 25 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Types of CIP Systems: 1. Single-use System – Uses fresh cleaning solutions each time. 2. Recovery System – Reuses cleaning solutions to reduce cost. 3. Manual CIP – Operator-controlled steps. 4. Automated CIP – Fully programmed and monitored cleaning cycles. CIP is Commonly Used For: Bioreactors, Mixing vessels, Pipelines, Heat exchangers, Storage tanks.
- 26. 26 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Advantages of CIP: No need to disassemble equipment. Reduces cleaning time and labor. Ensures consistent and repeatable cleaning. Reduces human error. Easily validated and documented. Regulatory Requirements: Must follow GMP and regulatory guidelines (FDA, EU, WHO). CIP process should be validated. Cleaning records must be documented.
- 27. 27 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Cleaning of Facilities: Cleaning of facilities refers to the systematic cleaning and sanitization of all rooms, surfaces, walls, ceilings, floors, HVAC systems, and supporting utilities within a pharmaceutical manufacturing area. It is essential for maintaining a clean and controlled environment to ensure product safety, quality, and compliance with GMP. Why Cleaning of Facilities is Important: Prevents contamination and cross-contamination. Maintains a controlled cleanroom environment. Complies with regulatory standards (GMP, FDA, WHO)Ensures product quality and patient safety.
- 28. 28 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Cleaning of Facilities:
- 29. 29 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Areas That Require Cleaning: Manufacturing and packaging rooms. Storage and dispensing areas. Cleanrooms (classified zones) Washrooms and gowning areas. Ceilings, walls, floors, windows. Drains and HVAC ducts( Heating, Validation, Air conditioning)
- 30. 30 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Steps in Facility Cleaning: 1. Preparation: Wear proper gowning, gather cleaning tools 2. Dry Cleaning: Remove visible dust and waste 3. Wet Cleaning: Apply cleaning agent with approved method (mop/wipe) 4. Rinse: Use water to remove chemical residues 5. Disinfection: Apply disinfectant to surfaces 6. Final Inspection: Check for cleanliness and log activities
- 31. 31 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Cleaning Schedule: Daily: Product contact surfaces, floors, frequently touched areas Weekly: Walls, glass, doors Monthly/Periodic: Ceilings, lighting fixtures, HVAC grilles. Documentation Required: Cleaning SOPs Cleaning logs (date, time, area, agent used, personnel) Environmental monitoring records Change control (for any changes in cleaning method)
- 32. 32 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 Conclusion: Cleaning validation is a critical quality assurance process in pharmaceutical manufacturing. It ensures that all cleaning procedures effectively remove product residues, cleaning agents, and microbial contaminants from equipment and surfaces. It helps to prevent cross-contamination and ensures the safety, efficacy, and quality of pharmaceutical products. Cleaning validation is required to comply with regulatory standards such as those from the FDA, EMA, and WHO. It involves planning, execution, and analytical methods, along with established acceptance criteria.
- 33. 33 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 References: 1.ICH Q7. (2000). Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. International Council for Harmonisation. 2. ICH Q9. (2005). Quality Risk Management. International Council for Harmonisation. 3. EudraLex - Volume 4. (Annex 15). EU Guidelines for Good Manufacturing Practice for Medicinal Products. European Commission. 4. PIC/S PI 006-3. (2007). Recommendation on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation.
- 34. 34 RIPER AUTONOMOUS NAAC & NBA (UG) SIRO- DSIR Raghavendra Institute of Pharmaceutical Education and Research - Autonomous K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721